miRNA‑328 overexpression confers cisplatin resistance in non‑small cell lung cancer via targeting of PTEN

miRNA-328 过表达通过靶向 PTEN 导致非小细胞肺癌产生顺铂耐药性

阅读:8
作者:Chunmei Wang, Shijun Wang, Feng'e Ma, Weidan Zhang

Abstract

Chemotherapy resistance, the molecular mechanism of which is complex and has not been fully understood, poses a major challenge in the treatment of patients with non‑small cell lung cancer (NSCLC). The dysregulation of microRNAs (miRs) has been reported to serve a pivotal role in the development of cancer and drug resistance. In the present study, reverse transcription‑quantitative polymerase chain reaction analysis revealed a significant increase in miR‑328 and a significant decrease in phosphatase and tensin homolog (PTEN) mRNA expression levels within tumor tissues from patients with cisplatin‑resistant NSCLC compared with those of cisplatin‑sensitive NSCLC patients. In addition, there was a negative correlation between PTEN mRNA and the miR‑328 expression levels. In addition, higher miR‑328 expression levels, and lower PTEN mRNA and protein expression levels, were detected in cisplatin‑resistant A549 (A549rCDDP) cells when compared with in their parental cells. A549rCDDP cells demonstrated significantly higher cell viability compared with A549 cells following treatment with all concentrations of cisplatin tested (2, 4, 6 and 8 µM). Additionally, transfection of miR‑328 inhibitor significantly increased PTEN mRNA and protein expression levels. Furthermore, the present study predicted and confirmed PTEN, a well‑known tumor suppressor, as a direct target of miR‑328 in NSCLC cells via the online tool MiRanda and a dual luciferase assay, respectively. Cell viability assay and flow cytometry analysis demonstrated that inhibition of miR‑328 also induced cellular apoptosis and decreased cell proliferation in A549rCDDP cells treated with cisplatin. In conclusion, these results suggested that abnormal expression of miR‑328 may contribute to cisplatin resistance in NSCLC, and may be considered to be a novel therapeutic target and indicator for the treatment and prognosis of patients with NSCLC treated with cisplatin‑based chemotherapy.

特别声明

1、本页面内容包含部分的内容是基于公开信息的合理引用;引用内容仅为补充信息,不代表本站立场。

2、若认为本页面引用内容涉及侵权,请及时与本站联系,我们将第一时间处理。

3、其他媒体/个人如需使用本页面原创内容,需注明“来源:[生知库]”并获得授权;使用引用内容的,需自行联系原作者获得许可。

4、投稿及合作请联系:info@biocloudy.com。