MiR-489 suppresses tumor growth and invasion by targeting HDAC7 in colorectal cancer.

Gao, S; Liu, H; Hou, S; Wu, L; Yang, Z; Shen, J; Zhou, L; Zheng, S-S; Jiang, B

Gao, S; Liu, H; Hou, S; Wu, L; Yang, Z; Shen, J; Zhou, L; Zheng, S-S; Jiang, B.

Afiliação

Gao S; 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.
Liu H; Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan, 030013, China. gaoshengmail@163.com.
Hou S; Department of Colorectal Cancer, Shanxi Cancer Hospital and Institute, The Third People's Hospital of Shanxi Province, No. 3 Xinchun Road, Taiyuan, 030013, China.
Wu L; Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan, 030013, China.
Yang Z; Department of Colorectal Cancer, Shanxi Cancer Hospital and Institute, The Third People's Hospital of Shanxi Province, No. 3 Xinchun Road, Taiyuan, 030013, China.
Shen J; Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan, 030013, China.
Zhou L; Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou, 310003, China.
Zheng SS; Key Laboratory of Organ Transplantation, Hangzhou, 310003, China.
Jiang B; Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China.

Clin Transl Oncol ; 20(6): 703-712, 2018 Jun.

Article em En | MEDLINE | ID: mdl-29071516

RESUMO

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.

Assuntos

Biomarcadores Tumorais/metabolismo; Proliferação de Células; Neoplasias Colorretais/patologia; Histona Desacetilases/metabolismo; Neoplasias Hepáticas/secundário; MicroRNAs/genética; Recidiva Local de Neoplasia/patologia; Animais; Apoptose; Biomarcadores Tumorais/genética; Movimento Celular; Neoplasias Colorretais/genética; Neoplasias Colorretais/metabolismo; Progressão da Doença; Feminino; Regulação Neoplásica da Expressão Gênica; Histona Desacetilases/genética; Humanos; Neoplasias Hepáticas/genética; Neoplasias Hepáticas/metabolismo; Masculino; Camundongos; Camundongos Endogâmicos BALB C; Camundongos Nus; Pessoa de Meia-Idade; Invasividade Neoplásica; Recidiva Local de Neoplasia/genética; Recidiva Local de Neoplasia/metabolismo; Prognóstico; Taxa de Sobrevida; Células Tumorais Cultivadas; Ensaios Antitumorais Modelo de Xenoenxerto

Palavras-chave

Colorectal cancer; HDAC7; Tumor invasion; miR-489

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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Biomarcadores Tumorais / MicroRNAs / Proliferação de Células / Histona Desacetilases / Neoplasias Hepáticas / Recidiva Local de Neoplasia Tipo de estudo: Prognostic_studies Limite: Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Transl Oncol Ano de publicação: 2018 Tipo de documento: Article País de afiliação: China País de publicação: Itália

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