LncRNA NNT-AS1 affect progesterone resistance by regulating miR-542-3p/survivin axis in endometrial cancer | Guo | Clinical Surgery Research Communications

LncRNA NNT-AS1 affect progesterone resistance by regulating miR-542-3p/survivin axis in endometrial cancer

Chen Guo, Wei Zhao, Xiu-Fang Bao

Abstract


Background: Progestin is commonly used for young patients suffering from endometrial cancer, but more than 30% of patients with progestin treatment have presented progestin resistance. The previous study showed that lncRNA NNT-AS1 could play an important role in cervical cancer. This study aimed to investigate the expression of NNT-AS1 in progesterone resistance endometrial cancer and assess its possible molecular mechanism.

Methods: Establishment of progesterone resistant Ishikawa (Ishikawa-PR) cell line that are resistant to the growth-inhibitory effects of progestin in vitro. Protein and mRNA expression were determined by western blot and qRT-PCR, respectively. MTT assay tested cell proliferation. Silence and overexpression of NNT-AS1 and survivin were performed by si-NNT-AS1/survivin and pcDNA-NNT-AS1/survivin, respectively. The effect of NNT-AS1 on Ishikawa-PR cell transplant tumor growth was measured by mice xenograft model. In addition, we evaluated the relationship between NNT-AS1 and miR-542-3p by RNA immunoprecipitation (RIP) and RNA pull down.

Results: The NNT-AS1 and survivin expression were both significantly increased, while miR-542-3p was decreased in Ishikawa-PR cell. Overexpression of NNT-AS1 was found to increase sensitive Ishikawa cells resistance, while inhibition of NNT-AS1 could reduce Ishikawa-PR cell resistance. NNT-AS1 functioned as a miR-542-3p decoy, and miR-542-3p could regulated Ishikawa cell resistance by survivin. In addition, NNT-AS1 was confirmed to regulate survivin expression and Ishikawa cell resistance by miR-542-3p. In vivo mice xenograft model revealed that silencing NNT-AS1 could improve endometrial cancer resistance.

Conclusion: LncRNA NNT-AS1 affect progesterone resistance by regulating miR-542-3p/survivin axis in endometrial cancer.

Keywords: LncRNA NNT-AS1; progesterone resistance; endometrial cancer; miR-524-3p; survivin;




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