LncRNA FAM83A-AS1 facilitates tumor proliferation and the migration via the HIF-1?/ glycolysis axis in lung adenocarcinoma.
Background: Lung adenocarcinoma (LUAD), the major subtype of lung cancer, is among the leading cause of cancer-related death worldwide. Energy-related metabolic reprogramming metabolism is a hallmark of cancer shared by numerous cancer types, including LUAD. Nevertheless, the functional pathways and molecular mechanism by which FAM83A-AS1 acts in metabolic reprogramming in ... lung adenocarcinoma have not been fully elucidated. Methods: We used transwell, wound-healing scratch assay, and metabolic assays to explore the effect of FAM83A-AS1 in LUAD cell lines. Western blotting, Co-IP assays, and ubiquitination assays were used to detect the effects of FAM83A-AS1 on HIF-1? expression, degradation, and its binding to VHL. Moreover, an in vivo subcutaneous tumor formation assay was used to detect the effect of FAM83A-AS1 on LUAD. Results: Herein, we identified FAM83A-AS1 as a metabolism-related lncRNA, which was highly correlated with glycolysis, hypoxia, and OXPHOS pathways in LUAD patients using bioinformatics analysis. In addition, we uncovered that FAM83A-AS1 could promote the migration and invasion of LUAD cells, as well as influence the stemness of LUAD cells in vivo and vitro. Moreover, FAM83A-AS1 was shown to promote glycolysis in LUAD cell lines in vitro and in vivo, and was found to influence the expression of genes related to glucose metabolism. Besides, we revealed that FAM83A-AS1 could affect glycolysis by regulating HIF-1? degradation. Finally, we found that FAM83A-AS1 knockdown could inhibit tumor growth and suppress the expression of HIF-1? and glycolysis-related genes in vivo. Conclusion: Our study demonstrates that FAM83A-AS1 contributes to LUAD proliferation and stemness via the HIF-1?/glycolysis axis, making it a potential biomarker and therapeutic target in LUAD patients.
Mesh Terms:
A549 Cells, Adenocarcinoma of Lung, Animals, Cell Proliferation, Gene Expression Regulation, Neoplastic, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Lung Neoplasms, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Neoplasm Proteins, RNA, Long Noncoding, Warburg Effect, Oncologic, Xenograft Model Antitumor Assays
A549 Cells, Adenocarcinoma of Lung, Animals, Cell Proliferation, Gene Expression Regulation, Neoplastic, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Lung Neoplasms, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Neoplasm Proteins, RNA, Long Noncoding, Warburg Effect, Oncologic, Xenograft Model Antitumor Assays
Int J Biol Sci
Date: Jan. 11, 2022
PubMed ID: 35002507
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