1. c-MYC/METTL3/LINC01006 positive feedback loop promotes migration, invasion and proliferation of non-small cell lung cancer.
- Author
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Liu C, Ren Q, Deng J, Wang S, and Ren L
- Subjects
- Humans, Animals, Neoplasm Invasiveness genetics, Epithelial-Mesenchymal Transition genetics, Epithelial-Mesenchymal Transition physiology, Cell Line, Tumor, Proto-Oncogene Proteins c-myc genetics, Proto-Oncogene Proteins c-myc metabolism, Gene Expression Regulation, Neoplastic genetics, Feedback, Physiological, Mice, MicroRNAs genetics, MicroRNAs metabolism, Adenosine analogs & derivatives, Adenosine metabolism, Adenosine genetics, Carcinoma, Non-Small-Cell Lung genetics, Carcinoma, Non-Small-Cell Lung pathology, Carcinoma, Non-Small-Cell Lung metabolism, Methyltransferases genetics, Methyltransferases metabolism, Cell Proliferation genetics, Cell Proliferation physiology, Cell Movement genetics, RNA, Long Noncoding genetics, RNA, Long Noncoding metabolism, Lung Neoplasms genetics, Lung Neoplasms pathology
- Abstract
Background: 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)., Materials and Methods: 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., Results: 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., Conclusions: 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., Competing Interests: Conflicts of interest The authors have no relevant financial or non-financial interests to disclose., (© 2023 The Authors. Published by Elsevier B.V. on behalf of Chang Gung University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)
- Published
- 2024
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