Xiaoqiang Zhang1, Xianju He2, Yunbing Liu3, Huiqing Zhang4, He Chen5, Shanxian Guo6, Yonggang Liang7. 1. Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, PR China. 2. Department of Emergency and Critical Care Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, PR China. 3. Department of Oncology, Ganxian District People's Hospital, Ganzhou, Jiangxi, 341100, PR China. 4. Department of Internal Medicine 2, Jiangxi Cancer Hospital, Nanchang, Jiangxi, 330029, PR China. 5. Jiangxi Key Laboratory of Molecular Medicine, Nanchang, Jiangxi, 330006, PR China. 6. Department of Internal Medicine 2, Jiangxi Cancer Hospital, Nanchang, Jiangxi, 330029, PR China. Electronic address: guoshanxian0830@126.com. 7. Department of Thoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, 330006, PR China. Electronic address: Doctor.Liang@outlook.com.
Abstract
BACKGROUND: MiR-101-3p is an important tumor suppressor miRNA in many human cancers. This study was to investigate the role of miR-101-3p in the progression of non-small cell lung cancer (NSCLC) and its potential underlying mechanism. METHODS: In this study, the endogenous expression of miR-101-3p or MALAT-1 in cells was modulated by cell transfection assays. The regulatory interaction of miR-101-3p and MALAT-1 was examined by Luciferase reporter gene and RNA pull-down assays. The effect of miR-101-3p or MALAT-1 on NSCLC cells was evaluated by cell proliferation assays, wound-healing assays and transwell invasion assays. The mice tumor model was established to test the role of miR-101-3p and MALAT-1 in the growth and metastasis of NSCLC in vivo. RESULTS: The relative expression of miR-101-3p in NSCLC cells was significantly decreased; while MALAT-1 was significantly increased. Moreover, overexpression of miR-101-3p could significantly inhibit the proliferation, migration and invasion of NSCLC cells in vitro, as well as MALAT-1 expression. Further studies confirmed that miR-101-3p could specifically repress MALAT-1 expression through direct binding; MALAT-1 overexpression completely reversed the miR-101-3p-induced suppression on the viability, migration and invasion of NSCLC cells and MALAT-1 expression. Finally, we confirmed that miR-101-3p could block the MALAT-1-induced activation of PI3K/AKT signal pathway and resulted in the inhibition on the growth and metastasis of NSCLC cells in vivo. CONCLUSION: MiR-101-3p inhibited the growth and metastasis of NSCLC through blocking PI3K/AKT signal pathway by targeting MALAT-1.
BACKGROUND:MiR-101-3p is an important tumor suppressor miRNA in many humancancers. This study was to investigate the role of miR-101-3p in the progression of non-small cell lung cancer (NSCLC) and its potential underlying mechanism. METHODS: In this study, the endogenous expression of miR-101-3p or MALAT-1 in cells was modulated by cell transfection assays. The regulatory interaction of miR-101-3p and MALAT-1 was examined by Luciferase reporter gene and RNA pull-down assays. The effect of miR-101-3p or MALAT-1 on NSCLC cells was evaluated by cell proliferation assays, wound-healing assays and transwell invasion assays. The micetumor model was established to test the role of miR-101-3p and MALAT-1 in the growth and metastasis of NSCLC in vivo. RESULTS: The relative expression of miR-101-3p in NSCLC cells was significantly decreased; while MALAT-1 was significantly increased. Moreover, overexpression of miR-101-3p could significantly inhibit the proliferation, migration and invasion of NSCLC cells in vitro, as well as MALAT-1 expression. Further studies confirmed that miR-101-3p could specifically repress MALAT-1 expression through direct binding; MALAT-1 overexpression completely reversed the miR-101-3p-induced suppression on the viability, migration and invasion of NSCLC cells and MALAT-1 expression. Finally, we confirmed that miR-101-3p could block the MALAT-1-induced activation of PI3K/AKT signal pathway and resulted in the inhibition on the growth and metastasis of NSCLC cells in vivo. CONCLUSION:MiR-101-3p inhibited the growth and metastasis of NSCLC through blocking PI3K/AKT signal pathway by targeting MALAT-1.