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

[ Vol. 21 , Issue. 8 ]

Author(s):

Tongqing Xue, Gang Yin, Weixuan Yang, Xiaoyu Chen, Cheng Liu, Weixi Yang* and Jun Zhu*Pages 702-712 (11)

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.

Affiliation:

Department of Interventional Radiology, Huaian Hospital of Huaian City, Huaian 223200, Jiangsu, Department of Interventional Radiology, Second People's Hospital of Huaian City, Huaian 223002, Jiangsu, Department of Digestive Medicine, Huaiyin Hospital of Huaian City, Huaian 223200, Jiangsu, Department of Radiology, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huaian 223001, Jiangsu, Department of Interventional Radiology, Huaian Hospital of Huaian City, Huaian 223200, Jiangsu, Department of Burns and Plastic Surgery, First Hospital of Huaian City, Huaian 223300, Jiangsu, Department of Interventional Radiology, The Third People’s Hospital of Yancheng, Yancheng 224001, Jiangsu

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