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Long Non-coding RNA PVT1 Competitively Binds MicroRNA-424-5p to Regulate CARM1 in Radiosensitivity of Non-Small-Cell
1Department of Medical Oncology, Chinese PLA General Hospital, Beijing 100853, China; Department of Oncology, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao 028000, China.
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.
Insights
Long non-coding RNA PVT1 promotes non-small-cell lung cancer (NSCLC) radiosensitivity. Silencing PVT1 or increasing microRNA-424-5p enhances NSCLC radiosensitivity by targeting the PVT1/CARM1 pathway.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Dysregulated long non-coding RNAs (lncRNAs) are implicated in cancer development.
- Non-small-cell lung cancer (NSCLC) radiosensitivity is a critical factor in treatment efficacy.
Purpose of the Study:
- To investigate the role of lncRNA PVT1 in NSCLC radiosensitivity.
- To elucidate the molecular mechanism involving the microRNA (miR)-424-5p/lncRNA PVT1/CARM1 signaling pathway.
Main Methods:
- Bioinformatic analysis to identify differentially expressed lncRNAs and co-expressed genes.
- Cell culture and transfection with mimics, inhibitors, and siRNAs targeting PVT1 and miR-424-5p.
- RNA immunoprecipitation (RIP) assay to confirm PVT1-CARM1 interaction.
- Assessment of cell proliferation, migration, invasion, cell cycle, and apoptosis.
Main Results:
- lncRNA PVT1 was significantly upregulated in NSCLC and associated with radiosensitivity.
- PVT1 and CARM1 were found to interact with miR-424-5p.
- Silencing PVT1 or overexpressing miR-424-5p inhibited NSCLC cell proliferation, migration, and invasion while promoting apoptosis.
Conclusions:
- lncRNA PVT1 promotes NSCLC radiosensitivity through the miR-424-5p/lncRNA PVT1/CARM1 pathway.
- Targeting PVT1 or enhancing miR-424-5p expression can improve NSCLC radiosensitivity.
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