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Long Non-coding RNA PVT1 Competitively Binds MicroRNA-424-5p to Regulate CARM1 in Radiosensitivity of Non-Small-Cell Lung Cancer

Dong Wang, Yi Hu

Molecular Therapy: Nucleic Acids · 2019

doi:10.1016/j.omtn.2018.12.006 (opens in a new tab)

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Abstract

Accumulating evidence revealed that dysregulated long non-coding RNAs (lncRNAs) were involved in tumorigenesis and progression. This study is supposed to reveal the effects of lncRNA PVT1 on the radiosensitivity of non-small-cell lung cancer (NSCLC) via the microRNA (miR)-424-5p/lncRNA PVT1/CARM1 signaling pathway. Differentially expressed lncRNA was filtrated. The co-expressed gene of lncRNA was predicted, and gene ontology analysis was performed to find out the genes associated with NSCLC radiosensitivity. The miR that was combined with lncRNA and mRNA was filtrated. Two cell lines with the highest expressed PVT1 were selected, followed by transfection with a series of different mimic, inhibitor, or siRNA. RIP assay was employed for the interaction between PVT1 and CARM1. The regulatory effect of miR-424-5p on cell proliferation, migration, invasion, cycle, and apoptosis was investigated. PVT1 was the most remarkable lncRNA that upregulated in NSCLC. CARM1 co-expressed with lncRNA PVT1 and associated with NSCLC radiosensitivity. Both lncRNA PVT1 and CARM1 can combine with miR-424-5p. Increased PVT1, CARM1, MMP-2, MMP-9, and Bcl-2 and decreased miR-424-5p and Bax were found in NSCLC tissues. PVT1 was targeted by miR-424-5p. After silencing of PVT1 or overexpressed miR-424-5p, decreased PVT1, CARM1, MMP-2, MMP-9, and Bcl-2 inhibited cell proliferation, migration, and invasion but promoted miR-424-5p, Bax, and cell apoptosis. The present study confirms the radiosensitivity of NSCLC radiotherapy can be increased by siRNA-PVT1 and overexpressed miR-424-5p. Keywords: non-small-cell lung cancer, long non-coding plasmacytoma variant translocation 1, microRNA-424-5p, co-activator-associated arginine methyltransferase 1, radiosensitivity

Abstract licence: CC BY-NC

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