Downregulation of microRNA­33a promotes cyclin­dependent kinase 6, cyclin D1 and PIM1 expression and gastric cancer cell proliferation.

Wang, Yudong; Zhou, Xinliang; Shan, Baoen; Han, Jing; Wang, Feifei; Fan, Xiaojie; Lv, Yalei; Chang, Liang; Liu, Wei

Downregulation of microRNA33a promotes cyclindependent kinase 6, cyclin D1 and PIM1 expression and gastric cancer cell proliferation.

Wang, Yudong; Zhou, Xinliang; Shan, Baoen; Han, Jing; Wang, Feifei; Fan, Xiaojie; Lv, Yalei; Chang, Liang; Liu, Wei.

Afiliación

Wang Y; Department of Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Zhou X; Department of Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Shan B; Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Han J; Department of Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Wang F; Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Fan X; Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Lv Y; Department of Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Chang L; Department of Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.
Liu W; Department of Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China.

Mol Med Rep ; 12(5): 6491-500, 2015 Nov.

Article en En | MEDLINE | ID: mdl-26352175

RESUMEN

Although microRNA33 (miR33) family members are known to be involved in the regulation and balancing of cholesterol metabolism, fatty acid oxidation and insulin signaling, their functions in carcinogenesis are controversial and the underlying mechanisms have remained elusive. Gastric cancer is the fourth most common malignancy in the world; however, the dysregulation and function of miR33 family members in gastric cancer have not been extensively studied. The present study reported that a miR33 family member, miR33a, was significantly downregulated in gastric cancer tissues and gastric cancer cell lines. Of note, the expression of miR33a was inversely correlated with pathological differentiation and metastasis as well as gastric cancer biomarker CA199. A cellcounting kit8 assay showed that transfection of the SGC7901 gastric cell line with miR33aoverexpression plasmid inhibited the capability of the cells to proliferate. Furthermore, overexpression of miR33a led to cell cycle arrest of SGC7901 cells in G1 phase. In addition, a luciferase reporter assay showed that miR33a directly targeted cyclindependent kinase 6 (CDK6), cyclin D1 (CCND1) and serine/threonine kinase PIM1. In gastric cancer specimens, the reduced expression of miR33a was associated with increased expression of CDK6, CCND1 and PIM1. However, only PIM1 expression was significantly increased in cancer tissues compared with that in their adjacent tissues. The present study revealed that miR33a was downregulated in gastric cancer tissues and cell lines, while forced overexpression of miR33a decreased CDK6, CCND1 and PIM1 expression to inhibit gastric cancer cell proliferation by causing G1 phase arrest. miR33a overexpression may therefore resemble an efficient strategy for gastric cancer therapy.

Asunto(s)

Adenocarcinoma/genética; Ciclina D1/genética; Quinasa 6 Dependiente de la Ciclina/genética; Regulación Neoplásica de la Expresión Génica; MicroARNs/genética; Proteínas Proto-Oncogénicas c-pim-1/genética; Neoplasias Gástricas/genética; Adenocarcinoma/metabolismo; Adenocarcinoma/patología; Anciano; Antígenos de Carbohidratos Asociados a Tumores/genética; Antígenos de Carbohidratos Asociados a Tumores/metabolismo; Secuencia de Bases; Antígeno Carcinoembrionario/genética; Antígeno Carcinoembrionario/metabolismo; Línea Celular Tumoral; Movimiento Celular; Proliferación Celular; Ciclina D1/metabolismo; Quinasa 6 Dependiente de la Ciclina/metabolismo; Femenino; Puntos de Control de la Fase G1 del Ciclo Celular/genética; Humanos; Masculino; MicroARNs/antagonistas & inhibidores; MicroARNs/metabolismo; Persona de Mediana Edad; Datos de Secuencia Molecular; Estadificación de Neoplasias; Oligonucleótidos/genética; Oligonucleótidos/metabolismo; Proteínas Proto-Oncogénicas c-pim-1/metabolismo; Transducción de Señal; Neoplasias Gástricas/metabolismo; Neoplasias Gástricas/patología

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Adenocarcinoma / Regulación Neoplásica de la Expresión Génica / Ciclina D1 / MicroARNs / Quinasa 6 Dependiente de la Ciclina / Proteínas Proto-Oncogénicas c-pim-1 Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Mol Med Rep Año: 2015 Tipo del documento: Article Pais de publicación: Grecia

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