S Gao1,2, H Liu3,4, S Hou3,4, L Wu5,6,7, Z Yang5,6,7, J Shen8, L Zhou5,6,7, S-S Zheng5,6,7, B Jiang3,4. 1. Department of Colorectal Cancer, Shanxi Cancer Hospital and Institute, The Third People's Hospital of Shanxi Province, No. 3 Xinchun Road, Taiyuan, 030013, China. gaoshengmail@163.com. 2. Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan, 030013, China. gaoshengmail@163.com. 3. Department of Colorectal Cancer, Shanxi Cancer Hospital and Institute, The Third People's Hospital of Shanxi Province, No. 3 Xinchun Road, Taiyuan, 030013, China. 4. Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan, 030013, China. 5. Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, 310003, China. 6. Key Laboratory of Organ Transplantation, Hangzhou, 310003, China. 7. Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China. 8. Department of General Surgery, Licheng County People's Hospital, Licheng, 647600, China.
Abstract
PURPOSE: The expression of miR-489 is linked to tumor development and progression; nevertheless, its role in tumor growth and invasion of colorectal cancer (CRC) and the underlying mechanism has not been clarified. EXPERIMENTAL DESIGN: We used quantitative RT-PCR to measure the expression of mature miR-489 in human colorectal tissues and the corresponding CRCs. Targets of miR-489 were predicted with TargetScan and substantiated by dual-luciferase reporter assay. Furthermore, we did in vitro and in vivo analysis with expression vectors and small interfering RNAs, to elucidate the precise role of miR-489 and its target gene histone deacetylase 7 (HDAC7) on cell proliferation, survival, and invasion. RESULTS: Compared to the corresponding non-tumor tissues, miR-489 was frequently downregulated in CRC. By Kaplan-Meier analysis, we found that lower CRC recurrence free survival years in the group with elevated miR-489 expression than those with lower miR-489 expression. In addition, we examined that miR-489 obviously inhibited the migratory and invasive capability in CRC. In further study, we found that miR-489 targets the 3'-UTR of the HDAC7 transcript and downregulates its expression, and HDAC7 expression promoted tumor cell proliferation and invasion. We demonstrated that miR-489 suppresses tumor invasion and metastasis in CRC by targeting HDAC7. CONCLUSIONS: We identified that MiR-489 suppresses tumor growth and invasion in CRC by targeting HDAC7. The expression of miR-489 suggests CRC recurrence and metastasis, which shed crucial light on how miR-489 functions in CRC pathogenesis.
PURPOSE: The expression of miR-489 is linked to tumor development and progression; nevertheless, its role in tumor growth and invasion of colorectal cancer (CRC) and the underlying mechanism has not been clarified. EXPERIMENTAL DESIGN: We used quantitative RT-PCR to measure the expression of mature miR-489 in human colorectal tissues and the corresponding CRCs. Targets of miR-489 were predicted with TargetScan and substantiated by dual-luciferase reporter assay. Furthermore, we did in vitro and in vivo analysis with expression vectors and small interfering RNAs, to elucidate the precise role of miR-489 and its target gene histone deacetylase 7 (HDAC7) on cell proliferation, survival, and invasion. RESULTS: Compared to the corresponding non-tumor tissues, miR-489 was frequently downregulated in CRC. By Kaplan-Meier analysis, we found that lower CRC recurrence free survival years in the group with elevated miR-489expression than those with lower miR-489expression. In addition, we examined that miR-489 obviously inhibited the migratory and invasive capability in CRC. In further study, we found that miR-489 targets the 3'-UTR of the HDAC7 transcript and downregulates its expression, and HDAC7 expression promoted tumor cell proliferation and invasion. We demonstrated that miR-489 suppresses tumor invasion and metastasis in CRC by targeting HDAC7. CONCLUSIONS: We identified that MiR-489 suppresses tumor growth and invasion in CRC by targeting HDAC7. The expression of miR-489 suggests CRC recurrence and metastasis, which shed crucial light on how miR-489 functions in CRC pathogenesis.
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