Journal Article

c-MYC/METTL3/LINC01006 positive feedback loop promotes migration, invasion and proliferation of non-small cell lung cancer

Ren, Qiang, Liu, Chunfeng, Wang, Songping, Deng, Jun, Ren, Lei

2024

Overview

This study aims to clarify the N6-methyladenosine (m6A) modification of LINC01006, which is involved in migration, invasion and proliferation of non-small cell lung cancer (NSCLC). LINC01006 and METTL3 expressions were analyzed in TCGA-LUAD cohort. Colony formation assay, wound-healing assay and transwell assay were performed to evaluate the ability of colony formation, migration and invasion. Q-PCR and western blot analysis determined gene expressions. M6A-RNA immunoprecipitation and m6A quantification assay were used to evaluate m6A modification. qChIP assay was used to validate transcriptional target. Luciferase assay validated the miRNA targets and transcriptional targets. In-situ xenograft model were included to evaluate tumor proliferation in vivo. LINC01006 and METTL3 expressions were elevated in NSCLC cells and tissues. LINC01006 promoted the migration and invasion of NSCLC via epithelial - mesenchymal transition (EMT). The expression of LINC01006 was positively correlated to the expression of METTL3. METTL3 promoted tumor formation and proliferation in the in-situ xenograft model of NSCLC. The expression of LINC01006 was increased by METTL3 via m6A modification. c-MYC directly induced METTL3. Both c-MYC and LINC01006 were commonly targeted by miR-34a/b/c and miR-2682, and thereby c-MYC/METTL3/LINC01006 formed a positive feedback loop through miRNA targets in NSCLC. LINC01006 is an oncogenic lncRNA, which induces migration, invasion and proliferation of NSCLC. METTL3 increases LINC01006 expression through stabilizing LINC01006 mRNA. c-MYC, as a transcription factor, activates METTL3, which results in an elevated level of LINC01006. c-MYC, METTL3 and LINC01006 form a positive feedback loop through multiple miRNA targets in NSCLC.

• Publisher: Elsevier Limited,Chang Gung University
• Subject: Adenosine - analogs & derivatives / Adenosine - genetics / Adenosine - metabolism / Animals / Antibodies / Assaying / c-Myc protein / Cancer / Cancer therapies / Carcinoma, Non-Small-Cell Lung - genetics / Carcinoma, Non-Small-Cell Lung - metabolism / Carcinoma, Non-Small-Cell Lung - pathology / Cell Line, Tumor / Cell Movement - genetics / Cell Proliferation - genetics / Cell Proliferation - physiology / Cells / Epithelial-Mesenchymal Transition - genetics / Epithelial-Mesenchymal Transition - physiology / Feedback / Feedback loops / Feedback, Physiological / Gene expression / Gene Expression Regulation, Neoplastic - genetics / Humans / Immunoprecipitation / Lung cancer / Lung Neoplasms - genetics / Lung Neoplasms - pathology / Metastasis / Methyltransferases - genetics / Methyltransferases - metabolism / Mice / MicroRNAs / MicroRNAs - genetics / MicroRNAs - metabolism / miRNA / Myc protein / N6-methyladenosine / Neoplasm Invasiveness - genetics / Non-small cell lung carcinoma / Original / Positive feedback / Proteins / Proto-Oncogene Proteins c-myc - genetics / Proto-Oncogene Proteins c-myc - metabolism / RNA, Long Noncoding - genetics / RNA, Long Noncoding - metabolism / Small cell lung carcinoma / Transcription factors / Tumors / Wound healing / Xenografts / Xenotransplantation