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Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Research Article

MiR-129-5p Promotes Radio-sensitivity of NSCLC Cells by Targeting SOX4 and RUNX1

Author(s): Tongqing Xue, Gang Yin, Weixuan Yang, Xiaoyu Chen, Cheng Liu, Weixi Yang* and Jun Zhu*

Volume 21, Issue 8, 2021

Published on: 15 April, 2021

Page: [702 - 712] Pages: 11

DOI: 10.2174/1568009621666210415094350

Price: $65

Abstract

Background: Dysregulation of microRNAs (miRNAs) figures prominently in the radio- sensitivity of non-small cell lung cancer (NSCLC). MiR-129-5p can block the development of a variety of tumors. However, whether miR-129-5p modulates radio-sensitivity of NSCLC cells remains unknown.

Objective: This study was aimed to explore the role and the underlying mechanism of miR-129-5p in the radiosensitivity of NSCLC.

Methods: Radio-resistant NSCLC cell lines (A549-R and H1299-R) were constructed using A549 and H1299 cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to quantify miR-129-5p, SRY-box transcription factor 4 (SOX4) mRNA, and RUNX family transcription factor 1 (RUNX1) mRNA expression levels. Cell apoptosis and cell cycle were detected by flow cytometry. Cell counting kit-8 (CCK-8) assay and colony formation experiments were used to measure cell proliferation. γ-H2AX was examined by Western blot to confirm DNA injury. Dual- luciferase reporter experiments were applied to analyze the interactions among miR-129-5p, RUNX1, and SOX4.

Results: In A549-R and H1299-R cells, compared with the wild-type cell lines, miR-129-5p expression was remarkably reduced while SOX4 and RUNX1 expressions were increased. The transfection of miR-129-5p into NSCLC cell lines markedly induced cell apoptosis, DNA injury, cell cycle arrest, and inhibited cell proliferation and colony formation. RUNX1 and SOX4 were validated as target genes of miR-129-5p, and the restoration of RUNX1 or SOX4 could counteract the influence of miR-129-5p on A549-R cells.

Conclusions: MiR-129-5p sensitizes A549-R and H1299-R cells to radiation by targeting RUNX1 and SOX4.

Keywords: NSCLC, miR-129-5p, RUNX1, SOX4, radiosensitivity, qTR-PCR.

Graphical Abstract
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