miR-1269b Drives Cisplatin Resistance of Human Non-Small Cell Lung Cancer via Modulating the PTEN/PI3K/AKT Signaling Pathway

Onco Targets Ther. 2020 Jan 7;13:109-118. doi: 10.2147/OTT.S225010. eCollection 2020.

Abstract

Background: MiRNAs have been reported to induce certain drug resistance in multiple solid tumors via various mechanisms. Our study aimed to investigate whether miRNA-1269b was involved in the chemoresistance and the progression of non-small cell lung cancer (NSCLC).

Methods: MTT and colony formation assay were conducted to determine cell proliferation and cell apoptosis was analyzed by flow cytometry with annexin V/PI. Luciferase reporter assay was performed to validate miRNA-targeting sequences. The function of miR-1269b in cisplatin-resistant was evaluated in vivo in a mouse tumor model.

Results: We found that miR-1269b expression was up-regulated in cisplatin-resistant NSCLC specimens and NSCLC cell lines, which resulted in the promotion of chemoresistance and tumorigenicity. miR-1269b overexpression enhanced drug resistance and promoted cell proliferation in vitro and tumor growth in vivo, with reduced apoptosis rate of A549 cells inin vitro cell culture. Mechanistically, we identified PTEN as the direct target of miR-1269b, and the PTEN level was negatively correlated with miR-1269b in NSCLC specimens. Further study demonstrated that miR-1269b targeted PTEN to modulate PI3K/AKT signaling pathway.

Conclusion: In conclusion, these findings suggest that the miR-1269b/PTEN/PI3K/AKT-mediated network might promote cisplatin resistance in NSCLC, and that miR-1269b can be a potential therapeutic target for chemoresistance in NSCLC patients.

Keywords: NSCLC; PI3K/AKT signaling; PTEN; cisplatin resistant; miR-1269b.

Grant support

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.