Fanlu Meng1, Linlin Zhang2. 1. DepartmentofMedicalOncology, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, China. Electronic address: mengfanlu1101@163.com. 2. DepartmentofMedicalOncology, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, China.
Abstract
BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. Previous studies revealed that miR-183-5p is frequently involved in various human cancers. However, the exact role of miR-183-5p in regulating the pathogenesis of lung cancer remains unclear. METHOD: Bioinformatic analysis, luciferase reporter assay, and Western blotting was used to investigate whether miR-183-5p directly bound to the 3'UTR of PIK3CA and prevented its translation. Furthermore, an si-miR-183-5p and PIK3CA siRNA was used to evaluate whether PIK3CA expression increased and whether cell proliferation, migration and invasion ability were promoted. RESULTS: miR-183-5p directly bound to the 3'UTR of PIK3CA and prevented its translation. miR-183-5p also acted as a tumor suppressor, and contrary to most studies, its expression was downregulated in lung cancer. Functional studies revealed that overexpression of miR-183-5p reduced cell proliferation, migration, and invasion and that miR-183-5p induced cell cycle arrest and increased cell apoptosis. PIK3CA expression, cell proliferation, migration and invasion ability increased. siRNA-mediated silencing of PIK3CA in lung cancer cells decreased their proliferation and invasive capabilities, suggesting that miR-183-5p inhibited cell proliferation and invasion of lung cancer cells at least partly through downstream targeting of PIK3CA. CONCLUSION: Our studies suggest that miR-183-5p may function as a tumor suppressor in lung cancer via the miR-183-5p/PIK3CA regulatory axis and identify a potentially effective therapeutic strategy for lung cancer.
BACKGROUND:Lung cancer is the leading cause of cancer-related death worldwide. Previous studies revealed that miR-183-5p is frequently involved in various humancancers. However, the exact role of miR-183-5p in regulating the pathogenesis of lung cancer remains unclear. METHOD: Bioinformatic analysis, luciferase reporter assay, and Western blotting was used to investigate whether miR-183-5p directly bound to the 3'UTR of PIK3CA and prevented its translation. Furthermore, an si-miR-183-5p and PIK3CA siRNA was used to evaluate whether PIK3CA expression increased and whether cell proliferation, migration and invasion ability were promoted. RESULTS:miR-183-5p directly bound to the 3'UTR of PIK3CA and prevented its translation. miR-183-5p also acted as a tumor suppressor, and contrary to most studies, its expression was downregulated in lung cancer. Functional studies revealed that overexpression of miR-183-5p reduced cell proliferation, migration, and invasion and that miR-183-5p induced cell cycle arrest and increased cell apoptosis. PIK3CA expression, cell proliferation, migration and invasion ability increased. siRNA-mediated silencing of PIK3CA in lung cancer cells decreased their proliferation and invasive capabilities, suggesting that miR-183-5p inhibited cell proliferation and invasion of lung cancer cells at least partly through downstream targeting of PIK3CA. CONCLUSION: Our studies suggest that miR-183-5p may function as a tumor suppressor in lung cancer via the miR-183-5p/PIK3CA regulatory axis and identify a potentially effective therapeutic strategy for lung cancer.