Involvement of miR-4262 in paclitaxel resistance through the regulation of PTEN in non-small cell lung cancer. Issue 7 (24th July 2019)

• Record Type: Journal Article
• Authors: Sun, Hongwen; Zhou, Xiaoting; Bao, Yanan; Xiong, Guosheng; Cui, Yue; Zhou, Hua
• Is Part Of: Open biology. Volume 9:Issue 7(2019)
• Publication Date: 2019-07-24
• Subjects: non-small cell lung cancer -- paclitaxel -- miRNA-4262 -- PTEN -- PI3 K/Akt pathway; Biology -- Periodicals; 570
• DOI: 10.1098/rsob.180227
• Languages: English
• ISSNs: 2046-2441

Abstract

Abstract : Abstract : Non-small cell lung cancer (NSCLC) is considered to be the primary cause of cancer-related mortalities worldwide. Paclitaxel (PTX), either as a monotherapy or in combination with other drugs, is an alternative therapy for advanced NSCLC. However, cancer cell resistance against PTX represents a major clinical problem. This study aimed to investigate the role and underlying mechanism of miR-4262 in PTX-resistant NSCLC. The levels of miR-4262 were analysed by quantitative reverse transcription polymerase chain reaction. A luciferase reporter assay and bioinformatics were used to explore the potential target gene of miR-4262. Regulation of miR-4262 and PTEN expressions in NSCLC was conducted by transfection. PTX-resistant A549 and H1299 cells were established by stepwise screening through increasing the PTX concentration in the cultures. In vivo, tumorigenesis experiments were used to explore the effects of miR-4262 and PTX. Cell proliferation, apoptosis and cell migration were detected using a CCK-8 assay, flow cytometry and Transwell migration assay, respectively. PI3 K/Akt pathway-related proteins were detected by western blot. miR-4262 expression was significantly upregulated in NSCLC tissues and cell lines, and miR-4262 targeted PTEN. In addition, miR-4262 induced PTX chemoresistance by promoting survival and migration in A549/PTX and H1299/PTX cells. Moreover, miR-4262 expression and PI3 K/Akt signalling pathway-related proteins were upregulated and PTEN was downregulated in A549/PTX and H1299/PTX. Our results indicate that miR-4262 enhances PTX resistance in NSCLC cells through targeting PTEN and activating the PI3 K/Akt signalling pathway. The inhibition of miR-4262 expression might be an improved treatment to overcome PTX resistance in NSCLC.