Long Noncoding RNA Cancer Susceptibility Candidate 9 Promotes Chemotherapy Resistance of Non-Small Cell Lung Cancer

生物 小RNA 癌症研究 吉非替尼 癌症 细胞生长 癌细胞 细胞 流式细胞术 肺癌 活力测定 分子生物学 基因 医学 表皮生长因子受体 病理 遗传学
作者
Ding Zhu Chen,Yi Zhang,Yong Lin,Yu Zhen Huang,Zhi Jian Zhang,Ji Guang Zhou,Qing Tian,Jun Biao Chen
出处
期刊:Indian Journal of Pharmaceutical Sciences [OMICS Publishing Group]
卷期号:83
标识
DOI:10.36468/pharmaceutical-sciences.spl.307
摘要

To investigate the molecular mechanism of long noncoding RNA cancer susceptibility candidate 9 involved in gefitinib resistance in non-small cell lung cancer cells by regulating microRNA-382-5p/ phosphoinositidedependent protein kinase-1/mammalian target of rapamycin complex 2 signal axis. 10 cases of serum before treatment and 10 cases of drug resistant serum after gefitinib treatment were collected from December 2019 to December 2020. The expression levels in non-small cell lung cancer tissues or cell lines were detected by real-time quantitative reverse transcription polymerase chain reaction. Cell counting kit 8, transwell and cell flow cytometry were used to detect the sensitivity of non-small cell lung cancer cells to gifetinib. Double luciferase reporter assay was used to verify the targeting relationship and the regulatory relationship was detected by western blotting and real-time quantitative reverse transcription polymerase chain reaction. Cancer susceptibility candidate 9 was highly expressed in non-small cell lung cancer tissues and drug-resistant HCC827/G cells. Overexpression of cancer susceptibility candidate 9 can significantly promote the proliferation, invasion and inhibit apoptosis of HCC827/G cells. At the same time, dual luciferase reporter assay confirmed that cancer susceptibility candidate 9 could negatively regulate the expression of microRNA-382-5p and microRNA-185-5p could bind to the 3'UTR of phosphoinositidedependent protein kinase-1 and mammalian target of rapamycin complex 2 and negatively regulate the expression of phosphoinositide-dependent protein kinase-1 and mammalian target of rapamycin complex 2. Further experiments showed that cancer susceptibility candidate 9 could up regulate the drug resistance of HCC827/G cells to gefitinib by down regulating the inhibition of microRNA-382-5p on phosphoinositide-dependent protein kinase-1 and mammalian target of rapamycin complex 2, thereby promoting the proliferation, invasion and inhibiting apoptosis of HCC827/G cells. Cancer susceptibility candidate 9 induces gefitinib resistance in non-small cell lung cancer cells by regulating microRNA-382- 5p/phosphoinositide-dependent protein kinase-1/mammalian target of rapamycin complex 2 signal axis.

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