X L Ren1,2, G Y He3,4, X M Li5,6, Hui Men7,8, L Z Yi9, G F Lu10,11, S N Xin12,13, P X Wu14,15, Y L Li16,17, W T Liao18,19, Y Q Ding20,21, L Liang22,23. 1. Department of Pathology, Southern Medical University, Guangzhou City, 510515, Guangdong Province, People's Republic of China. 419750459@qq.com. 2. Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou City, 510515, Guangdong Province, People's Republic of China. 419750459@qq.com. 3. Department of Pathology, Southern Medical University, Guangzhou City, 510515, Guangdong Province, People's Republic of China. 506343091@qq.com. 4. Department of Pathology, Xinxiang Medical University, Xinxiang City, 453003, Henan Province, People's Republic of China. 506343091@qq.com. 5. Department of Pathology, Southern Medical University, Guangzhou City, 510515, Guangdong Province, People's Republic of China. 656088404@qq.com. 6. Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou City, 510515, Guangdong Province, People's Republic of China. 656088404@qq.com. 7. Department of Pathology, Southern Medical University, Guangzhou City, 510515, Guangdong Province, People's Republic of China. 18987057@qq.com. 8. Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou City, 510515, Guangdong Province, People's Republic of China. 18987057@qq.com. 9. Department of Gastroenterology, Leshan People's Hospital, Leshan City, 614000, Sichuan Province, People's Republic of China. 651218437@qq.com. 10. Department of Pathology, Southern Medical University, Guangzhou City, 510515, Guangdong Province, People's Republic of China. 531946910@qq.com. 11. Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou City, 510515, Guangdong Province, People's Republic of China. 531946910@qq.com. 12. Department of Pathology, Southern Medical University, Guangzhou City, 510515, Guangdong Province, People's Republic of China. 631079663@qq.com. 13. Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou City, 510515, Guangdong Province, People's Republic of China. 631079663@qq.com. 14. Department of Pathology, Southern Medical University, Guangzhou City, 510515, Guangdong Province, People's Republic of China. 815561320@qq.com. 15. Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou City, 510515, Guangdong Province, People's Republic of China. 815561320@qq.com. 16. Department of Pathology, Southern Medical University, Guangzhou City, 510515, Guangdong Province, People's Republic of China. 985667529@qq.com. 17. Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou City, 510515, Guangdong Province, People's Republic of China. 985667529@qq.com. 18. Department of Pathology, Southern Medical University, Guangzhou City, 510515, Guangdong Province, People's Republic of China. 30221424@qq.com. 19. Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou City, 510515, Guangdong Province, People's Republic of China. 30221424@qq.com. 20. Department of Pathology, Southern Medical University, Guangzhou City, 510515, Guangdong Province, People's Republic of China. dyq@fimmu.com. 21. Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou City, 510515, Guangdong Province, People's Republic of China. dyq@fimmu.com. 22. Department of Pathology, Southern Medical University, Guangzhou City, 510515, Guangdong Province, People's Republic of China. 651218437@qq.com. 23. Guangdong Province Key Laboratory of Molecular Tumor Pathology, Guangzhou City, 510515, Guangdong Province, People's Republic of China. 651218437@qq.com.
Abstract
BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in the world. MicroRNAs play important roles in the progression of CRC. This study aimed to investigate the role of miR-206 and its novel mechanism in the invasion and metastasis of CRC. METHODOLOGY: Real-time RT-PCR or Western blotting was used to detect the expressions of miR-206, FMNL2 and c-MET in CRC cell lines and tissues. Luciferase reporter assays were conducted to detect the associations between miR-206 and 3'UTRs of FMNL2 and c-MET. A series of loss-of-function and gain-of-function assays were performed to evaluate the effect of miR-206 on the proliferation, invasion and metastasis of CRC cells. RESULTS: miR-206 was significantly down-regulated in CRC tissues and correlated closely with differentiation, lymphatic metastasis and serosal invasion. miR-206 suppressed CRC cell proliferation by arresting CRC cells in the G1/G0 phase and accelerating apoptosis. miR-206 also inhibited cell invasion and lung metastasis in CRC cells. Mechanically, FMNL2 and c-MET were identified as direct targets of miR-206. And FMNL2 rescued the suppression of miR-206 in the proliferation and invasion of CRC cells. CONCLUSIONS: This study revealed functional and mechanistic links between miR-206 and oncogene FMNL2 and c-MET in the progression of CRC. miR-206 functioned as a tumor suppressor in the progression of CRC by targeting FMNL2 and c-MET. Restoration of miR-206 expression may represent a promising therapeutic approach for targeting malignant CRC.
BACKGROUND:Colorectal cancer (CRC) is one of the most common cancers in the world. MicroRNAs play important roles in the progression of CRC. This study aimed to investigate the role of miR-206 and its novel mechanism in the invasion and metastasis of CRC. METHODOLOGY: Real-time RT-PCR or Western blotting was used to detect the expressions of miR-206, FMNL2 and c-MET in CRC cell lines and tissues. Luciferase reporter assays were conducted to detect the associations between miR-206 and 3'UTRs of FMNL2 and c-MET. A series of loss-of-function and gain-of-function assays were performed to evaluate the effect of miR-206 on the proliferation, invasion and metastasis of CRC cells. RESULTS:miR-206 was significantly down-regulated in CRC tissues and correlated closely with differentiation, lymphatic metastasis and serosal invasion. miR-206 suppressed CRC cell proliferation by arresting CRC cells in the G1/G0 phase and accelerating apoptosis. miR-206 also inhibited cell invasion and lung metastasis in CRC cells. Mechanically, FMNL2 and c-MET were identified as direct targets of miR-206. And FMNL2 rescued the suppression of miR-206 in the proliferation and invasion of CRC cells. CONCLUSIONS: This study revealed functional and mechanistic links between miR-206 and oncogene FMNL2 and c-MET in the progression of CRC. miR-206 functioned as a tumor suppressor in the progression of CRC by targeting FMNL2 and c-MET. Restoration of miR-206 expression may represent a promising therapeutic approach for targeting malignant CRC.
Authors: Jordan M Cummins; Yiping He; Rebecca J Leary; Ray Pagliarini; Luis A Diaz; Tobias Sjoblom; Omer Barad; Zvi Bentwich; Anna E Szafranska; Emmanuel Labourier; Christopher K Raymond; Brian S Roberts; Hartmut Juhl; Kenneth W Kinzler; Bert Vogelstein; Victor E Velculescu Journal: Proc Natl Acad Sci U S A Date: 2006-02-27 Impact factor: 11.205
Authors: Jan D Haas; Kiran Nistala; Franziska Petermann; Namita Saran; Vijaykumar Chennupati; Susanne Schmitz; Thomas Korn; Lucy R Wedderburn; Reinhold Förster; Andreas Krueger; Immo Prinz Journal: PLoS One Date: 2011-05-26 Impact factor: 3.240
Authors: Dóra Mihály; Gergő Papp; Zsolt Mervai; Andrea Reszegi; Péter Tátrai; Gábor Szalóki; Johanna Sápi; Zoltán Sápi Journal: Exp Biol Med (Maywood) Date: 2018-08-15