Epigenetic mechanisms of the influence of aging on the development of breast cancer with the participation of retroelements
Abstract
Breast cancer is the most common malignant neoplasm in women worldwide. In 5–15% of cases, the disease is monogenic, caused by heterozygous germline mutations in the BRCA1, BRCA2, ATM, BARD1, CHEK2, RAD51D, RAD51C, PALB2 genes. Most cases of breast cancer are multifactorial diseases associated with multiple SNPs, many of which are located in intergenic and intronic regions where retroelement genes and non-coding RNA genes are located. Therefore, it can be assumed that breast cancer-associated SNPs exert their influence on cancer development by changing the properties of retroelements and non-coding RNAs. The risk of breast cancer increases with age. At the same time, the activation factor of retroelements is aging, during which their progressive epigenetic derepression occurs, contributing to the imbalance of complementary non-coding RNAs (due to the origin in evolution from retroelement sequences and formation from their transcripts by processing). An analysis of scientific literature confirms this assumption: in breast cancer, a change in the expression of 43 oncogenic microRNAs derived from retroelements (among which 17 microRNAs are characterized by impaired expression during aging) and 43 oncosuppressor microRNAs (among which 13 microRNAs are characterized by impaired expression during aging) was detected. Knowledge of the mechanisms of involvement of the described microRNAs not only in carcinogenesis, but also in physiological aging, will allow the competent use of microRNAs in targeted therapy of breast cancer with minimal side effects in relation to the development and differentiation of human organs and tissues.
References
Mak JKL, McMurran CE, Kuja-Halkola R, Hall P, Czene K, Jylhävä J, et al. Clinical biomarker-based biological aging and risk of cancer in the UK Biobank. Br J Cancer, 2023, 129(1): 94-103.
Bai H, Liu X, Lin M, Meng Y, Tang R, Guo Y, et al. Progressive senescence programs induce intrinsic vulnerability to aging-related female breast cancer. Nat Commun, 2024, 15(1): 5154.
Chang L, Weiner LS, Hartman SJ, Horvath S, Jeste D, Mischel PS, et al. Breast cancer treatment and its effects on aging. J Geriatr Oncol, 2019, 10(2): 346-355. doi: 10.1016/j.jgo.2018.07.010.
Zhu J, Wang F, Shi L, Cai H, Zheng Y, Zheng W, et al. Accelerated aging in breast cancer survivors and its association with mortality and cancer recurrence. Breast Cancer Res Treat, 2020, 180(2): 449-459.
Sokolova A, Johnstone KJ, McCart Reed AE, Simpson PT, Lakhani SR. Hereditary breast cancer: syndromes, tumour pathology and molecular testing. Histopathology, 2023, 82(1): 70-82.
Michailidou K, Beesley J, Lindstrom S, Canisius S, Dennis J, Lush MJ, et al. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer. Nat Genet, 2015, 47(4): 373-80.
Zhang H, Ahearn TU, Lecarpentier J, Barnes D, Beesley J, Antoniou AC, et al. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses. Nat Genet, 2020, 52(6): 572-581.
Yong SY, Raben TG, Lello L, Hsu SDH. Genetic architecture of complex traits and disease risk predictors. Sci Rep, 2020, 10(1): 12055.
Nurk S, Koren S, Rhie A, Rautiainen M, Bzikadze AV, Mikheenko A, et al. The complete sequence of a human genome. Science, 2022, 376(6588): 44-53.
Mustafin RN. The role of transposable elements in the association of polymorphic variants with multifactorial diseases. Opera Medica et Physiologica, 2024, 11(4): 60-70.
Park EG, Ha H, Lee DH, Kim WR, Lee YJ, Bae WH, et al. Genomic Analyses of Non-Coding RNAs Overlapping Transposable Elements and Its Implication to Human Diseases. Int J Mol Sci, 2022, 23(16): 8950.
Zabihi N, Sadeghi S, Tabatabaeian H, Ghaedi K, Azadeh M, Fazilati M. The association between rs1972820 and the risk of breast cancer in Isfahan population. J Cancer Res Ther, 2017, 13(1): 26-32.
Rybarczyk A, Lehmann T, Iwańczyk-Skalska E, Juzwa W, Pławski A, Kopciuch K, et al. In silico and in vitro analysis of the impact of single substitutions within EXO-motifs on Hsa-MiR-1246 intercellular transfer in breast cancer cell. J Appl Genet, 2023, 64(1): 105-124.
Dai YC, Pan Y, Quan MM, Chen Q, Pan Y, Ruan YY, et al. MicroRNA-1246 Mediates Drug Resistance and Metastasis in Breast Cancer by Targeting NFE2L3. Front Oncol, 2021, 11: 677168.
Gorbunova V, Seluanov A, Mita P, McKerrow W, Fenyö D, Boeke JD, et al. The role of retrotransposable elements in ageing and age-associated diseases. Nature, 2021, 596(7870): 43-53.
Yu C, Zhang T, Chen F, Yu Z. The impact of hsa-miR-1972 on the expression of von Willebrand factor in breast cancer progression regulation. PeerJ, 2024, 12: e18476.
Turashvili G, Lightbody ED, Tyryshkin K, SenGupta SK, Elliott BE, Madarnas Y, et al. Novel prognostic and predictive microRNA targets for triple-negative breast cancer. FASEB J, 2018: fj201800120R.
Al-Khanbashi M, Caramuta S, Alajmi AM, Al-Haddabi I, Al-Riyami M, Lui WO, et al. Tissue and Serum miRNA Profile in Locally Advanced Breast Cancer (LABC) in Response to Neo-Adjuvant Chemotherapy (NAC) Treatment. PLoS One, 2016, 11(4): e0152032.
Kankava K, Kvaratskhelia E, Burkadze G, Kokhreidze I, Gogokhia N, Abzianidze E. LINE-1 methylation in blood and tissues of patients with breast cancer. Georgian Med News, 2018, 276: 107-112.
van Hoesel AQ, van de Velde CJ, Kuppen PJ, Liefers GJ, Putter H, Sato Y, et al. Hypomethylation of LINE-1 in primary tumor has poor prognosis in young breast cancer patients: a retrospective cohort study. Breast Cancer Res Treat, 2012, 134(3): 1103-14.
Park SY, Seo AN, Jung HY, Gwak JM, Jung N, Cho N, et al. Alu and LINE-1 hypomethylation is associated with HER2 enriched subtype of breast cancer. PLoS One, 2014, 9(6): e100429.
Jiang JC, Rothnagel JA, Upton KR. Widespread Exaptation of L1 Transposons for Transcription Factor Binding in Breast Cancer. Int J Mol Sci, 2021, 22(11): 5625.
Berrino E, Miglio U, Bellomo SE, Debernardi C, Bragoni A, Petrelli A, et al. The Tumor-Specific Expression of L1 Retrotransposons Independently Correlates with Time to Relapse in Hormone-Negative Breast Cancer Patients. Cells, 2022, 11(12): 1944.
Jang HS, Shah NM, Du AY, Dailey ZZ, Pehrsson EC, Godoy PM, et al. Transposable elements drive widespread expression of oncogenes in human cancer. Nat Genet, 2019, 51: 611-617.
Rodriguez-Martin B, Alvarez EG, Baez-Ortega A, Zamora J, Supek F, Demeulemeester J, et al. Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition. Nat Genet, 2020, 52: 306–319.
Ramos KS, Montoya-Durango DE, Teneng I, Nanez A, Stribinskis V. Epigenetic control of embryonic renal cell differentiation by L1 retrotransposon. Birth Defects Res A Clin Mol Teratol, 2011, 91(8): 693-702.
Shukla R, Upton KR, Muñoz-Lopez M, Gerhardt DJ, Fisher ME, Nguyen T, et al. Endogenous retrotransposition activates oncogenic pathways in hepatocellular carcinoma. Cell, 2013, 153(1): 101-11.
Xia Z, Cochrane DR, Anglesio MS, Wang YK, Nazeran T, Tessier-Cloutier B, et al. LINE-1 retrotransposon-mediated DNA transductions in endometriosis associated ovarian cancer. Gynecol Oncol, 2017, 147(3): 642-647.
Cajuso T, Sulo P, Tanskanen T, Katainen R, Taira A, Hänninen UA, et al. Retrotransposon insertions can initiate colorectal cancer and are associated with poor survival. Nat Commun, 2019; 10(1): 4022.
Aschacher T, Wolf B, Enzmann F, Kienzl p, Messner B, Sampl S, et al. LINE-1 induces hTERT and ensures telomere maintenance in tumour cell lines. Oncogene, 2016, 35(1): 94-104.
Nair M.G., Ramesh R.S., Naidu C.M., Mavatkar AD, Snijesh VP, Ramamurthy V, et al. Estimation of ALU Repetitive Elements in Plasma as a Cost-Effective Liquid Biopsy Tool for Disease Prognosis in Breast Cancer. Cancers (Basel), 2023, 15(4): 1054.
Bolkestein M, Wong JKL, Thewes V, Körber V, Hlevnjak M, Elgaafary S, et al. Chromothripsis in Human Breast Cancer. Cancer Res, 2020, 80(22): 4918-4931.
Vasmatzis G, Wang X, Smadbeck JB, Murphy SJ, Geiersbach KB, Johnson SH, et al. Chromoanasynthesis is a common mechanism that leads to ERBB2 amplifications in a cohort of early stage HER2+ breast cancer samples. BMC Cancer, 2018, 18(1): 738.
Fazza AC, Sabino FC, de Setta N, Bordin NA Jr, da Silva EH, et al. Estimating genomic instability mediated by Alu retroelements in breast cancer. Genet Mol Biol, 2009, 32(1): 25-31.
Chisholm KM, Aubert SD, Freese KP, Zakian VA, King MC, Welcsh PL. A genomewide screen for suppressors of Alu-mediated rearrangements reveals a role for PIF1. PLoS One, 2012, 7(2): e30748.
Denariyakoon S, Puttipanyalears C, Chatamra K, Mutirangura A. Breast Cancer Sera Changes in Alu Element Methylation Predict Metastatic Disease Progression. Cancer Diagn Progn, 2022, 2(6): 731-738.
Chen Y, Salas LA, Marotti JD, Jenkins NP, Cheng C, Miller TW, et al. Extensive epigenomic dysregulation is a hallmark of homologous recombination deficiency in triple-negative breast cancer. Int J Cancer, 2025, 156(6): 1191-1202.
Gelaleti GB, Granzotto A, Leonel C, Jardim BV, Moschetta MG, Carareto CM, et al. Short interspersed CAN SINE elements as prognostic markers in canine mammary neoplasia. Oncol Rep, 2014, 31(1): 435-41.
Park JE, Kim HW, Yun SH, Kim SJ. Ginsenoside Rh2 upregulates long noncoding RNA STXBP5-AS1 to sponge microRNA-4425 in suppressing breast cancer cell proliferation. J Ginseng Res, 2021, 45(6): 754-762.
Abd El Hafeez HA, Abd El Rahman MZ, Kamel TM, Rezk KM, Mohamed FM, Abdel-Hameed ZA. The role of circulating cell-free DNA and its integrity as a biomarker for diagnosis of breast cancer using ALU (247/115) bP sequences. Egypt J Immunol, 2023, 30(3): 44-55.
Özgür E, Ferhatoğlu F, Şen F, Gezer U. Effect of Cytotoxic Therapy on ALU Expression is Modulated by Hormonal Status in Patients with Breast Cancer. Balkan Med J, 2022, 39(6): 450-451. PMID: 36205400.
Özgür E, Ferhatoglu F, Sen F, Saip P, Gezer U. Expression of alu repeat in blood plasma of patients with breast cancer during neoadjuvant chemotherapy: an exploratory study. Exp Oncol, 2023, 45(1): 120-124.
Song R, Guo P, Ren X, Zhou L, Li P, Rahman NA, et al. A novel polypeptide CAPG-171aa encoded by circCAPG plays a critical role in triple-negative breast cancer. Mol Cancer, 2023, 22(1): 104.
Wang X, Chen T, Li C, Li W, Zhou X, Li Y, et al. CircRNA-CREIT inhibits stress granule assembly and overcomes doxorubicin resistance in TNBC by destabilizing PKR. J Hematol Oncol, 2022, 15(1): 122.
Wu Q, Nie DY, Ba-Alawi W, Ji Y, Zhang Z, Cruickshank J, et al. PRMT inhibition induces a viral mimicry response in triple-negative breast cancer. Nat Chem Biol, 2022, 18(8): 821-830.
Cheng J, Cuk K, Heil J, Golatta M, Schott S, Sohn C, et al. Cell-free circulating DNA integrity is an independent predictor of impending breast cancer recurrence. Oncotarget, 2017, 8(33): 54537-54547.
Annapragada AV, Niknafs N, White JR, Bruhm DC, Cherry C, Medina JE, et al. Genome-wide repeat landscapes in cancer and cell-free DNA. Sci Transl Med, 2024, 16(738): eadj9283.
Ono M, Kawakami M, Ushikubo H. Stimulation of expression of the human endogenous retrovirus genome by female steroid hormones in human breast cancer cell line T47D. J Virol, 1987, 61(6): 2059-62.
Wang-Johanning F, Frost AR, Johanning GL, Khazaeli MB, LoBuglio AF, Shaw DR, et al. Expression of human endogenous retrovirus k envelope transcripts in human breast cancer. Clin Cancer Res, 2001, 7(6), 1553-60.
Wang-Johanning F, Frost AR, Jian B, Epp L, Lu DW, Johanning GL. Quantitation of HERV-K env gene expression and splicing in human breast cancer. Oncogene, 2003, 22(10), 1528-35.
Nguyen TD, Davis J, Eugenio RA, Liu Y. Female Sex Hormones Activate Human Endogenous Retrovirus Type K Through the OCT4 Transcription Factor in T47D Breast Cancer Cells. AIDS Res Hum Retroviruses, 2019, 35(3): 348-356.
Zhou F, Li M, Wei Y, Lin K, Lu Y, Shen J, Johanning GL, Wang-Johanning F. Activation of HERV-K Env protein is essential for tumorigenesis and metastasis of breast cancer cells. Oncotarget, 2016, 7: 84093–84117.
Wang T, Zeng J, Lowe CB, Sellers RG, Salama SR, Yang M, et al. Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53. Proc Natl Acad Sci U S A, 2007, 104(47): 18613-8.
Pollock NC, Ramroop JR, Hampel H, Troester MA, Conway K, Hu JJ, et al. Differences in somatic TP53 mutation type in breast tumors by race and receptor status. Breast Cancer Res Treat, 2022, 192(3): 639-648.
Arancio W, Coronnello C. Repetitive Sequence Transcription in Breast Cancer. Cells, 2022, 11(16): 2522.
Lu X, Sachs F, Ramsay L, Jacques PÉ, Göke J, Bourque G, et al. The retrovirus HERVH is a long noncoding RNA required for human embryonic stem cell identity. Nat Struct Mol Biol, 2014, 21(4): 423-5.
Rivas SR, Valdez MJM, Govindarajan V, Seetharam D, Doucet-O'Hare TT, Heiss JD, et al. The Role of HERV-K in Cancer Stemness. Viruses, 2022, 14(9): 2019.
Mustafin R.N. The Relationship between Transposons and Transcription Factors in the Evolution of Eukaryotes. Journal of Evolutionary Biochemistry and Physiology, 2019, 55(1): 14-22. (in Rus.).
Babaian A, Romanish MT, Gagnier L, Kuo LY, Karimi MM, Steidl C, et al. Onco-exaptation of an endogenous retroviral LTR drives IRF5 expression in Hodgkin lymphoma. Oncogene, 2016, 35(19): 2542-6.
Lock FE, Rebollo R, Miceli-Royer K, Nemirovsky O, Serrano I, Steidl C, et al. Distinct isoform of FABP7 revealed by screening for retroelement-activated genes in diffuse large B-cell lymphoma. Proc Natl Acad Sci, 2014, 111: E3534–E3543.
Scarfò I, Pellegrino E, Mereu E, Chuang NT, Vertino PM, Devine SE. Identification of a new subclass of ALK-negative ALCL expressing aberrant levels of ERBB4 transcripts. Blood, 2016, 127: 221–32.
Wiesner T, Lee W, Obenauf AC, Ran L, Murali R, Berger MF, et al. Alternative transcription initiation leads to expression of a novel ALK isoform in cancer. Nature, 2015, 526: 453–7.
Bouras A, Leone M, Bonadona V, Lebrun M, Calender A, Boutry-Kryza N. Identification and Characterization of New Alu Element Insertion in the BRCA1 Exon 14 Associated with Hereditary Breast and Ovarian Cancer. Genes (Basel), 2021, 12(11): 1736.
Mustafin R.N., Khusnutdinova E.K. The role of retroelements in the development of hereditary tumor syndromes. Advances in Molecular Oncology, 2021, 8(4): 42–52. (In Russ.).
Mustafin R.N. Participation of retroelements in chromoanagenesis in cancer development. Siberian Journal of Oncology, 2024, 23(5): 146–156. (In Rus.).
Ji X, Zhao S. DA and Xiao-two giant and composite LTR-retrotransposon-like elements identified in the human genome, Genomics, 2008, 91: 249-258.
Liang B, Yan T, Wei H, Zhang D, Li L, Liu Z, et al. HERVK-mediated regulation of neighboring genes: implications for breast cancer prognosis. Retrovirology, 2024, 21(1): 4.
Lemaître C, Tsang J, Bireau C, Heidmann T, Dewannieux M. A human endogenous retrovirus-derived gene that can contribute to oncogenesis by activating the ERK pathway and inducing migration and invasion. PLoS Pathog, 2017, 13: e1006451.
Rhyu DW, Kang YJ, Ock MS, Eo JW, Choi YH, Kim WJ, et al. Expression of human endogenous retrovirus env genes in the blood of breast cancer patients. Int J Mol Sci, 2014, 15(6): 9173-83.
Johanning GL, Malouf GG, Zheng X, Esteva FJ, Weinstein JN, Wang-Johanning F, et al. Expression of human endogenous retrovirus-K is strongly associated with the basal-like breast cancer phenotype. Sci Rep, 2017, 7: 41960.
Wang-Johanning F, Li M, Esteva FJ, Hess KR, Yin B, Rycaj K, et al. Human endogenous retrovirus type K antibodies and mRNA as serum biomarkers of early-stage breast cancer. Int J Cancer, 2014, 134(3): 587-95.
De Koning AP, Gu W, Castoe TA, Batzer MA, Pollock DD. Repetitive Elements May Comprise Over Two-Thirds of the Human Genome. PLOS Genetics, 2011, 7: e1002384.
Chen Z, Gong X, Cheng C, Fu Y, Wu W, Luo Z. Circ_0001777 Affects Triple-negative Breast Cancer Progression Through the miR-95-3p/AKAP12 Axis. Clin Breast Cancer, 2023, 23(2): 143-154.
Yusof KM, Groen K, Rosli R, Abdullah M, Mahmud R, Avery-Kiejda KA. Evaluation of Circulating MicroRNAs and Adipokines in Breast Cancer Survivors with Arm Lymphedema. Int J Mol Sci, 2022, 23(19): 11359.
Wang Y, Yin W, Lin Y, Yin K, Zhou L, Du Y, et al. Downregulated circulating microRNAs after surgery: potential noninvasive biomarkers for diagnosis and prognosis of early breast cancer. Cell Death Discov, 2018, 4: 21.
Noren Hooten N, Fitzpatrick M, Wood WH 3rd, De S, Ejiogu N, et al. Age-related changes in microRNA levels in serum. Aging (Albany NY), 2013, 5(10): 725-40.
Wang H, Hu X, Yang F, Xiao H. miR-325-3p Promotes the Proliferation, Invasion, and EMT of Breast Cancer Cells by Directly Targeting S100A2. Oncol Res, 2021, 28(7): 731-744.
Zhao J, Li C, Qin T, Jin Y, He R, Sun Y, et al. Mechanical overloading-induced miR-325-3p reduction promoted chondrocyte senescence and exacerbated facet joint degeneration. Arthritis Res Ther, 2023, 25(1): 54.
Lindholm EM, Leivonen SK, Undlien E, Nebdal D, Git A, et al. miR-342-5p as a Potential Regulator of HER2 Breast Cancer Cell Growth. Microrna, 2019, 8(2): 155-165.
Owczarz M, Połosak J, Domaszewska-Szostek A, Kołodziej P, Kuryłowicz A, Puzianowska-Kuźnicka M. Age-related epigenetic drift deregulates SIRT6 expression and affects its downstream genes in human peripheral blood mononuclear cells. Epigenetics, 2020, 15(12): 1336-1347.
Yang Q, Zhao S, Shi Z, Cao L, Liu J, Pan T, et al. Chemotherapy-elicited exosomal miR-378a-3p and miR-378d promote breast cancer stemness and chemoresistance via the activation of EZH2/STAT3 signaling. J Exp Clin Cancer Res, 2021, 40(1): 120.
Guo D, Ye Y, Qi J, Tan X, Zhang Y, Ma Y, et al. Age and sex differences in microRNAs expression during the process of thymus aging. Acta Biochim Biophys Sin (Shanghai), 2017, 49(5): 409-419.
Zheng S, Li M, Miao K, Xu H. lncRNA GAS5-promoted apoptosis in triple-negative breast cancer by targeting miR-378a-5p/SUFU signaling. J Cell Biochem, 2020, 121(3): 2225-2235.
Kooistra SM, Nørgaard LC, Lees MJ, Steinhauer C, Johansen JV, Helin K. A screen identifies the oncogenic micro-RNA miR-378a-5p as a negative regulator of oncogene-induced senescence. PLoS One, 2014, 9(3): e91034.
Sun TY, Li YQ, Zhao FQ, Sun HM, Gao Y, Wu B, et al. MiR-1-3p and MiR-124-3p Synergistically Damage the Intestinal Barrier in the Ageing Colon. J Crohns Colitis, 2022, 16(4): 656-667.
Torrisi R, Vaira V, Giordano L, Fernandes B, Saltalamacchia G, Palumbo R, et al. Identification of a Panel of miRNAs Associated with Resistance to Palbociclib and Endocrine Therapy. Int J Mol Sci, 2024, 25(3): 1498.
Chacolla-Huaringa R, Moreno-Cuevas J, Trevino V, Scott SP. Entrainment of Breast Cell Lines Results in Rhythmic Fluctuations of MicroRNAs. Int J Mol Sci, 2017, 18(7):1499.
Jiang B, Xia J, Zhou X. Overexpression of lncRNA SLC16A1-AS1 Suppresses the Growth and Metastasis of Breast Cancer via the miR-552-5p/WIF1 Signaling Pathway. Front Oncol, 2022, 12: 712475.
Breunig S, Wallner V, Kobler K, Wimmer H, Steinbacher P, Streubel MK, et al. The life in a gradient: calcium, the lncRNA SPRR2C and mir542/mir196a meet in the epidermis to regulate the aging process. Aging (Albany NY), 2021, 13(15): 19127-19144.
Zhu H, Dai M, Chen X, Chen X, Qin S, Dai S. Integrated analysis of the potential roles of miRNA mRNA networks in triple negative breast cancer. Mol Med Rep, 2017, 16(2): 1139-1146.
Yu JM, Wu X, Gimble JM, Guan X, Freitas MA, Bunnell BA. Age-related changes in mesenchymal stem cells derived from rhesus macaque bone marrow. Aging Cell, 2011, 10(1): 66-79.
Li D, Hu A. LINC-PINT suppresses breast cancer cell proliferation and migration via MEIS2/PPP3CC/NF-κB pathway by sponging miR-576-5p. Am J Med Sci, 2024, 367(3): 201-211.
Ipson BR, Fletcher MB, Espinoza SE, Fisher AL. Identifying Exosome-Derived MicroRNAs as Candidate Biomarkers of Frailty. J Frailty Aging, 2018, 7(2): 100-103.
Zeng X, Ma X, Guo H, Wei L, Zhang Y, Sun C, et al. MicroRNA-582-5p promotes triple-negative breast cancer invasion and metastasis by antagonizing CMTM8. Bioengineered, 2021, 12(2): 10126-10135.
Zhang YF, Li XX, Cao XL, Ji CC, Gao XY, Gao D, et al. MicroRNA-582-5p Contributes to the Maintenance of Neural Stem Cells Through Inhibiting Secretory Protein FAM19A1. Front Cell Neurosci, 2022, 16: 866020.
Yuan C. miR-616 promotes breast cancer migration and invasion by targeting TIMP2 and regulating MMP signaling. Oncol Lett, 2019, 18(3): 2348-2355.
Wang B, Wang Y, Wang X, Gu J, Wu W, Wu H, et al. Extracellular Vesicles Carrying miR-887-3p Promote Breast Cancer Cell Drug Resistance by Targeting BTBD7 and Activating the Notch1/Hes1 Signaling Pathway. Dis Markers, 2022, 2022: 5762686.
Abd ELhafeez AS, Ghanem HM, Swellam M, Taha AM. Involvement of FAM170B-AS1, hsa-miR-1202, and hsa-miR-146a-5p in breast cancer. Cancer Biomark, 2024, 39(4): 313-333.
Gao W, Yuan L, Zhang Y, Huang F, Ai C, Lv T, et al. miR-1246-overexpressing exosomes improve UVB-induced photoaging by activating autophagy via suppressing GSK3β. Photochem Photobiol Sci, 2024, 23(5): 957-972.
Klinge CM, Piell KM, Tooley CS, Rouchka EC. HNRNPA2/B1 is upregulated in endocrine-resistant LCC9 breast cancer cells and alters the miRNA transcriptome when overexpressed in MCF-7 cells. Sci Rep, 2019, 9(1): 9430.
Zhou B, Xue J, Wu R, Meng H, Li R, Mo Z, et al. CREBZF mRNA nanoparticles suppress breast cancer progression through a positive feedback loop boosted by circPAPD4. J Exp Clin Cancer Res, 2023, 42(1): 138.
Dell'Aversana C, Cuomo F, Longobardi S, D'Hooghe T, Caprio F, Franci G, et al. Age-related miRNome landscape of cumulus oophorus cells during controlled ovarian stimulation protocols in IVF cycles. Hum Reprod, 2021, 36(5): 1310-1325.
Lv Z, Yang K, Wang Y. Long non-coding RNA breast cancer-associated transcript 54 sponges microRNA-1269b to suppress the proliferation of hemangioma-derived endothelial cells. Bioengineered, 2022, 13(3): 6188-6195.
Turkistani S, Sugita BM, Fadda P, Marchi R, Afsari A, et al. A panel of miRNAs as prognostic markers for African-American patients with triple negative breast cancer. BMC Cancer, 2021, 21(1): 861.
Somel M, Guo S, Fu N, Yan Z, Hu HY, Xu Y, et al. MicroRNA, mRNA, and protein expression link development and aging in human and macaque brain. Genome Res. 2010, 20(9): 1207-18.
Peng Z, Xu B, Jin F. Circular RNA hsa_circ_0000376 Participates in Tumorigenesis of Breast Cancer by Targeting miR-1285-3p. Technol Cancer Res Treat, 2020, 19: 1533033820928471.
Zhao D, Wu K, Sharma S, Xing F, Wu SY, Tyagi A, et al. Exosomal miR-1304-3p promotes breast cancer progression in African Americans by activating cancer-associated adipocytes. Nat Commun, 2022, 13(1): 7734.
Tu D, Dou J, Wang M, Zhuang H, Zhang X. M2 macrophages contribute to cell proliferation and migration of breast cancer. Cell Biol Int, 2021, 45(4): 831-838.
He YY, Xiao B, Qiu JH, Lei T, Li LH, Sun ZH. Study on the expression of microRNA-1825 in serum of pre-operative and post-operative patients with breast cancer. Zhonghua Yu Fang Yi Xue Za Zhi, 2021, 55(5): 691-697.
Singh J, Sangwan N, Chauhan A, Avti PK. Integrative Expression, Survival Analysis and Cellular miR-2909 Molecular Interplay in MRN Complex Check Point Sensor Genes (MRN-CSG) Involved in Breast Cancer. Clin Breast Cancer, 2022, 22(8): e850-e862.
Dong G, Wang X, Jia Y, Jia Y, Zhao W, Zhang J, et al. HAND2-AS1 Works as a ceRNA of miR-3118 to Suppress Proliferation and Migration in Breast Cancer by Upregulating PHLPP2. Biomed Res Int, 2020, 2020: 8124570.
Koleckova M, Ehrmann J, Bouchal J, Janikova M, Brisudova A, Srovnal J, et al. Epithelial to mesenchymal transition and microRNA expression are associated with spindle and apocrine cell morphology in triple-negative breast cancer. Sci Rep, 2021, 11(1): 5145.
Alberro A, Bravo-Miana RDC, Gs Iñiguez S, Iribarren-López A, Arroyo-Izaga M, Matheu A, et al. Age-Related sncRNAs in Human Hippocampal Tissue Samples: Focusing on Deregulated miRNAs. Int J Mol Sci, 2024, 25(23): 12872.
Lou W, Liu J, Ding B, Xu L, Fan W. Identification of chemoresistance-associated miRNAs in breast cancer. Cancer Manag Res, 2018, 10: 4747-4757.
Li Y, Shan F, Chen J. Lipid raft-mediated miR-3908 inhibition of migration of breast cancer cell line MCF-7 by regulating the interactions between AdipoR1 and Flotillin-1. World J Surg Oncol, 2017, 15(1): 69.
Sato J, Shimomura A, Kawauchi J, Matsuzaki J, Yamamoto Y, Takizawa S, et al. Brain metastasis-related microRNAs in patients with advanced breast cancer. PLoS One, 2019, 14(10): e0221538.
Machida T, Tomofuji T, Ekuni D, Maruyama T, Yoneda T, Kawabata Y, et al. MicroRNAs in Salivary Exosome as Potential Biomarkers of Aging. Int J Mol Sci, 2015, 16(9): 21294-309.
Carvalho TM, Brasil GO, Jucoski TS, Adamoski D, de Lima RS, Spautz CC, et al. MicroRNAs miR-142-5p, miR-150-5p, miR-320a-3p, and miR-4433b-5p in Serum and Tissue: Potential Biomarkers in Sporadic Breast Cancer. Front Genet, 2022, 13: 865472.
Boo L, Ho WY, Ali NM, Yeap SK, Ky H, Chan KG, et al. MiRNA Transcriptome Profiling of Spheroid-Enriched Cells with Cancer Stem Cell Properties in Human Breast MCF-7 Cell Line. Int J Biol Sci, 2016, 12(4): 427-45.
Popp NA, Yu D, Green B, Chew EY, Ning B, Chan CC, et al. Functional single nucleotide polymorphism in IL-17A 3' untranslated region is targeted by miR-4480 in vitro and may be associated with age-related macular degeneration. Environ Mol Mutagen, 2016, 57(1): 58-64.
Kwak SY, Yoo JO, An HJ, Bae IH, Park MJ, Kim J, et al. miR-5003-3p promotes epithelial-mesenchymal transition in breast cancer cells through Snail stabilization and direct targeting of E-cadherin. J Mol Cell Biol, 2016, 8(5): 372-383.
Sathipati SY, Tsai MJ, Aimalla N, Moat L, Shukla SK, Allaire P, et al. An evolutionary learning-based method for identifying a circulating miRNA signature for breast cancer diagnosis prediction. NAR Genom Bioinform, 2024, 6(1): lqae022.
Engel A, Wagner V, Hahn O, Foltz AG, Atkins M, Beganovic A, et al. A spatio-temporal brain miRNA expression atlas identifies sex-independent age-related microglial driven miR-155-5p increase. bioRxiv, 2025, 16: 2025.03.15.643430.
Tian X, Yu H, Li D, Jin G, Dai S, Gong P, et al. The miR-5694/AF9/Snail Axis Provides Metastatic Advantages and a Therapeutic Target in Basal-like Breast Cancer. Mol Ther, 2021, 29(3): 1239-1257.
Satomi-Tsushita N, Shimomura A, Matsuzaki J, Yamamoto Y, Kawauchi J, Takizawa S, et al. Serum microRNA-based prediction of responsiveness to eribulin in metastatic breast cancer. PLoS One, 2019, 14(9): e0222024.
Gao Y, Ma H, Gao C, Lv Y, Chen X, Xu R, et al. Tumor-promoting properties of miR-8084 in breast cancer through enhancing proliferation, suppressing apoptosis and inducing epithelial-mesenchymal transition. J Transl Med, 2018, 16(1): 38.
Moro J, Grinpelc A, Farré PL, Duca RB, Lacunza E, Grana KD, et al. miR-877-5p as a Potential Link between Triple-Negative Breast Cancer Development and Metabolic Syndrome. Int J Mol Sci, 2023, 24(23):16758. doi: 10.3390/ijms242316758.
Ding J, Wu W, Yang J, Wu M. Long non-coding RNA MIF-AS1 promotes breast cancer cell proliferation, migration and EMT process through regulating miR-1249-3p/HOXB8 axis. Pathol Res Pract, 2019, 215(7): 152376.
Ma L, Zhang Y, Hu F. miR 28 5p inhibits the migration of breast cancer by regulating WSB2. Int J Mol Med, 2020, 46(4): 1562-1570.
Chen Q, Xu H, Zhu J, Feng K, Hu C. LncRNA MCM3AP-AS1 promotes breast cancer progression via modulating miR-28-5p/CENPF axis. Biomed Pharmacother, 2020, 128: 110289.
Zan X, Li W, Wang G, Yuan J, Ai Y, Huang J, et al. Circ-CSNK1G1 promotes cell proliferation, migration, invasion and glycolysis metabolism during triple-negative breast cancer progression by modulating the miR-28-5p/LDHA pathway. Reprod Biol Endocrinol, 2022, 20(1): 138.
Poodineh J, Sirati-Sabet M, Rajabibazl M, Mohammadi-Yeganeh S. MiR-130a-3p blocks Wnt signaling cascade in the triple-negative breast cancer by targeting the key players at multiple points. Heliyon, 2020, 6(11): e05434.
Xie D, Li S, Wu T, Wang X, Fang L. MiR-181c suppresses triple-negative breast cancer tumorigenesis by targeting MAP4K4. Pathol Res Pract, 2022, 230: 153763.
Wang MH, Liu ZH, Zhang HX, Liu HC, Ma LH. Hsa_circRNA_000166 accelerates breast cancer progression via the regulation of the miR-326/ELK1 and miR-330-5p/ELK1 axes. Ann Med, 2024, 56(1): 2424515.
Yu S, Zhou Y, Niu L, Qiao Y, Yan Y. Mesenchymal stem cell-derived exosome mir-342-3p inhibits metastasis and chemo-resistance of breast cancer through regulating ID4. Genes Genomics, 2022, 44(5): 539-550.
Zhou D, Ren K, Wang M, Wang J, Li E, Hou C, et al. Long non-coding RNA RACGAP1P promotes breast cancer invasion and metastasis via miR-345-5p/RACGAP1-mediated mitochondrial fission. Mol Oncol, 2021, 15(2): 543-559.
Hao S, Tian W, Chen Y, Wang L, Jiang Y, Gao B, et al. MicroRNA-374c-5p inhibits the development of breast cancer through TATA-box binding protein associated factor 7-mediated transcriptional regulation of DEP domain containing 1. J Cell Biochem, 2019, 120(9): 15360-15368.
Y, Chen Y, Yao S, Deng G, Liu D, Yuan X, et al. MiR-422a weakened breast cancer stem cells properties by targeting PLP2. Cancer Biol Ther, 2018, 19(5): 436-444.
Zhao L, Feng X, Song X, Zhou H, Zhao Y, Cheng L, et al. miR-493-5p attenuates the invasiveness and tumorigenicity in human breast cancer by targeting FUT4. Oncol Rep, 2016, 36(2): 1007-15.
Qiu X, Zhang Q, Deng Q, Li Q. Circular RNA hsa_circ_0012673 Promotes Breast Cancer Progression via miR-576-3p/SOX4 Axis. Mol Biotechnol, 2023, 65(1): 61-71.
Sun L, Chen S, Wang T, Bi S. Hsa_circ_0008673 Promotes Breast Cancer Progression by MiR-578/GINS4 Axis. Clin Breast Cancer, 2023, 23(3): 281-290.
Yuan D, Liu J, Sang W, Li Q. Comprehensive analysis of the role of SFXN family in breast cancer. Open Med (Wars), 2023, 18(1): 20230685.
Zhang Z, Luo X, Xue X, Pang M, Wang X, Yu L, et al. Engineered Exosomes Carrying miR-588 for Treatment of Triple Negative Breast Cancer Through Remodeling the Immunosuppressive Microenvironment. Int J Nanomedicine, 2024, 19: 743-758.
Choi S, An HJ, Yeo HJ, Sung MJ, Oh J, Lee K, et al. MicroRNA 606 inhibits the growth and metastasis of triple negative breast cancer by targeting Stanniocalcin 1. Oncol Rep, 2024, 51(1): 2.
Yang T, Yu R, Cheng C, Huo J, Gong Z, Cao H, et al. Cantharidin induces apoptosis of human triple negative breast cancer cells through mir-607-mediated downregulation of EGFR. J Transl Med, 2023, 21(1): 597.
Bhajun R, Guyon L, Pitaval A, Sulpice E, Combe S, Obeid P, et al. A statistically inferred microRNA network identifies breast cancer target miR-940 as an actin cytoskeleton regulator. Sci Rep, 2015, 5: 8336.
Shi G, Li H, Chen Y, Chen Z, Lin X. CircSEPT9 promotes breast cancer progression by regulating PTBP3 expression via sponging miR-625-5p. Thorac Cancer, 2024, 15(10): 808-819.
Ren F, Rui X, Xiao X. Loss of miR-634 contributes to the formation FOXA1-positive triple negative breast cancer subtype. Discov Oncol, 2024, 15(1): 584.
Tang C, Wang X, Ji C, Zheng W, Yu Y, Deng X, et al. The Role of miR-640: A Potential Suppressor in Breast Cancer via Wnt7b/β-catenin Signaling Pathway. Front Oncol, 2021, 11: 645682.
Darvishi N, Rahimi K, Mansouri K, Fathi F, Menbari MN, Mohammadi G, et al. MiR-646 prevents proliferation and progression of human breast cancer cell lines by suppressing HDAC2 expression. Mol Cell Probes, 2020, 53: 101649.
Lee JW, Guan W, Han S, Hong DK, Kim LS, Kim H. MicroRNA-708-3p mediates metastasis and chemoresistance through inhibition of epithelial-to-mesenchymal transition in breast cancer. Cancer Sci, 2018, 109(5): 1404-1413.
Dong HT, Liu Q, Zhao T, Yao F, Xu Y, Chen B, et al. Long Non-coding RNA LOXL1-AS1 Drives Breast Cancer Invasion and Metastasis by Antagonizing miR-708-5p Expression and Activity. Mol Ther Nucleic Acids, 2020, 19: 696-705.
Zhou X, Jian W, Luo Q, Zheng W, Deng X, Wang X, et al. Circular RNA_0006014 promotes breast cancer progression through sponging miR-885-3p to regulate NTRK2 and PIK3/AKT pathway. Aging (Albany NY), 2022, 14(7): 3105-3128.
Xu C, Yu H, Yin X, Zhang J, Liu C, Qi H, et al. Circular RNA circNINL promotes breast cancer progression through activating β-catenin signaling via miR-921/ADAM9 axis. J Biochem, 2021, 169(6): 693-700.
Ji C, Zhu L, Fang L. Hsa_circ_0000851 promotes PDK1/p-AKT-mediated cell proliferation and migration by regulating miR-1183 in triple-negative breast cancer. Cell Signal, 2023, 101: 110494.
Torkashvand S, Damavandi Z, Mirzaei B, Tavallaei M, Vasei M, Mowla SJ. Decreased Expression of Bioinformatically Predicted piwil2-targetting microRNAs, miR-1267 and miR-2276 in Breast Cancer. Arch Iran Med, 2016, 19(6): 420-5.
Sameer C A, Shah M, Nandy D, Gupta R. Genomic Index of Sensitivity to Chemotherapy for Triple Negative Breast Cancer. Asian Pac J Cancer Prev, 2023, 24(6): 2043-2053.
Du HY, Liu B. MiR-1271 as a tumor suppressor in breast cancer proliferation and progression via targeting SPIN1. Eur Rev Med Pharmacol Sci, 2018, 22(9): 2697-2706.
Yu T, Yu HR, Sun JY, Zhao Z, Li S, Zhang XF, et al. miR-1271 inhibits ERα expression and confers letrozole resistance in breast cancer. Oncotarget, 2017, 8(63): 107134-107148.
Hironaka-Mitsuhashi A, Otsuka K, Gailhouste L, Sanchez Calle A, Kumazaki M, Yamamoto Y, et al. MiR-1285-5p/TMEM194A axis affects cell proliferation in breast cancer. Cancer Sci, 2020, 111(2): 395-405.
Chen K, Xiao X, Xu Z. MiR-1294 inhibits the progression of breast cancer via regulating ERK signaling. Bull Cancer, 2022, 109(10): 999-1006.
Liang Y, Song X, Li Y, Chen B, Zhao W, Wang L, et al. LncRNA BCRT1 promotes breast cancer progression by targeting miR-1303/PTBP3 axis. Mol Cancer. 2020, 19(1): 85.
Yu L, Zhang W, Wang P, Zhang Q, Cong A, Yang X, et al. LncRNA SNHG11 aggravates cell proliferation and migration in triple-negative breast cancer via sponging miR-2355-5p and targeting CBX5. Exp Ther Med, 2021, 22(2): 892.
Luo X, Wang H. LINC00514 upregulates CCDC71L to promote cell proliferation, migration and invasion in triple-negative breast cancer by sponging miR-6504-5p and miR-3139. Cancer Cell Int, 2021, 21(1): 180.
Delgir S, Ilkhani K, Safi A, Rahmati Y, Montazari V, Zaynali-Khasraghi Z, et al. The expression of miR-513c and miR-3163 was downregulated in tumor tissues compared with normal adjacent tissue of patients with breast cancer. BMC Med Genomics, 2021, 14(1): 180.
Wei M, Yu H, Cai C, Gao R, Liu X, Zhu H. MiR-3194-3p Inhibits Breast Cancer Progression by Targeting Aquaporin1. Front Oncol, 2020, 10: 1513.
Akshaya RL, Akshaya N, Selvamurugan N. A computational study of non-coding RNAs on the regulation of activating transcription factor 3 in human breast cancer cells. Comput Biol Chem, 2020, 89: 107386.
Wang B, Li J, Sun M, Sun L, Zhang X. miRNA expression in breast cancer varies with lymph node metastasis and other clinicopathologic features. IUBMB Life, 2014, 66(5): 371-7.
Li Y, Wang YW, Chen X, Ma RR, Guo XY, Liu HT, et al. MicroRNA-4472 Promotes Tumor Proliferation and Aggressiveness in Breast Cancer by Targeting RGMA and Inducing EMT. Clin Breast Cancer, 2020, 20(2): e113-e126.
Shin D, Yoo JO, Jeong JH, Han YH. MiR-5586-5p Suppresses Hypoxia-induced Angiogenesis Through Multiple Targeting of HIF-1α, HBEGF and ADAM17 in Breast Cancer. Anticancer Res, 2025, 45(2): 473-489.
Wang D, Yang S, Lyu M, Xu L, Zhong S, Yu D. Circular RNA HSDL2 promotes breast cancer progression via miR-7978 ZNF704 axis and regulating hippo signaling pathway. Breast Cancer Res, 2024, 26(1): 105.
Yentrapalli R, Azimzadeh O, Kraemer A, Malinowsky K, Sarioglu H, Becker KF, et al. Quantitative and integrated proteome and microRNA analysis of endothelial replicative senescence. J Proteomics, 2015, 126: 12-23.
Yoo JK, Kim CH, Jung HY, Lee DR, Kim JK. Discovery and characterization of miRNA during cellular senescence in bone marrow-derived human mesenchymal stem cells. Exp Gerontol, 2014, 58: 139-45.
Dalton S, Smith K, Singh K, Kaiser H, Kolhe R, Mondal AK, et al. Accumulation of kynurenine elevates oxidative stress and alters microRNA profile in human bone marrow stromal cells. Exp Gerontol, 2020, 130: 110800.
Chen J, Zou Q, Lv D, Wei Y, Raza MA, Chen Y, et al. Comprehensive transcriptional landscape of porcine cardiac and skeletal muscles reveals differences of aging. Oncotarget, 2017, 9(2): 1524-1541.
Mennitti LV, Carpenter AAM, Loche E, Pantaleão LC, Fernandez-Twinn DS, Schoonejans JM, et al. Effects of maternal diet-induced obesity on metabolic disorders and age-associated miRNA expression in the liver of male mouse offspring. Int J Obes (Lond), 2022, 46(2): 269-278.
Guo Y, Tian L, Liu X, He Y, Chang S, Shen Y. ERRFI1 Inhibits Proliferation and Inflammation of Nucleus Pulposus and Is Negatively Regulated by miR-2355-5p in Intervertebral Disc Degeneration. Spine (Phila Pa 1976), 2019, 44(15): E873-E881.
Morsiani C, Bacalini MG, Collura S, Moreno-Villanueva M, Breusing N, Bürkle A, et al. Blood circulating miR-28-5p and let-7d-5p associate with premature ageing in Down syndrome. Mech Ageing Dev, 2022, 206: 111691.
Manzano-Crespo M, Atienza M, Cantero JL. Lower serum expression of miR-181c-5p is associated with increased plasma levels of amyloid-beta 1-40 and cerebral vulnerability in normal aging. Transl Neurodegener, 2019, 8: 34.
Schneider A, Matkovich SJ, Victoria B, Spinel L, Bartke A, Golusinski P, et al. Changes of Ovarian microRNA Profile in Long-Living Ames Dwarf Mice during Aging. PLoS One, 2017, 12(1): e0169213.
Wang L, Si X, Chen S, Wang X, Yang D, Yang H, et al. A comprehensive evaluation of skin aging-related circular RNA expression profiles. J Clin Lab Anal, 2021, 35(4): e23714.
Zhang J, Gong H, Zhao T, Xu W, Chen H, Li T, et al. AMPK-upregulated microRNA-708 plays as a suppressor of cellular senescence and aging via downregulating disabled-2 and mTORC1 activation. MedComm (2020), 2024, 5(3): e475.
Yang Y, Zhang W, Wang X, Yang J, Cui Y, Song H, et al. A passage-dependent network for estimating the in vitro senescence of mesenchymal stromal/stem cells using microarray, bulk and single cell RNA sequencing. Front Cell Dev Biol, 2023, 11: 998666.
Huang WQ, Lin Q, Chen S, Sun L, Chen Q, Yi K, et al. Correction for: Integrated analysis of microRNA and mRNA expression profiling identifies BAIAP3 as a novel target of dysregulated hsa-miR-1972 in age-related white matter lesions. Aging (Albany NY), 2021, 13(11): 15688-15689.
Zou Y, Chen Y, Yao S, Deng G, Liu D, Yuan X, et al. MiR-422a weakened breast cancer stem cells properties by targeting PLP2. Cancer Biol Ther, 2018, 19(5): 436-444.