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Up-regulation of miR-592 correlates with tumor progression and poor prognosis in patients with colorectal cancer
Institution:1. Oncology Department of Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, No. 1 ShuaiFuYuan Hutong, Dongcheng District, Beijing 100730, People''s Republic of China;2. Peking Union Medical College, Chinese Academy of Medical Sciences, No. 5 DongDanSanTiao, Dongcheng District, Beijing 100005, People''s Republic of China;3. Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, People''s Republic of China;1. Institute for Innovation, Ajinomoto Co., Inc., 1-1, Suzuki-cho, Kawasaki-ku, Kawasaki City, Kanagawa 210-8681, Japan;2. R&D Planning Dept., EA Pharma Co., Ltd., 1-1 Irifune 2-chome, Chuo-ku, Tokyo 104-0042, Japan
Abstract:miR-592, as a potential biomarker, has been linked to several cancers. However, the expression level and prognostic value of miR-592 in CRC have not been elucidated. In this study, we detected the miR-592 expression in CRC serum, tumor tissues, adjacent non-tumor tissues (NATs) and four colorectal cancer cell lines by RT-PCR. Our data proved that miR-592 expression was up-regulated in clinical CRC serum and tissues (P < 0.05). Serum or tissue miR-592 in CRC metastatic patients also maintained a high level, compared to that in non-metastatic CRC patients (P < 0.05). After radical surgery, postoperative serum miR-592 level in CRC patients significantly decreased (P < 0.05). Our clinicopathological analysis revealed that high miR-592 was significant associated with the tumor size (P = 0.008), TNM stage (P = 0.026), distant metastasis (P = 0.004) and preoperative CEA level (P = 0.022), which led to a shorter overall survival rate in CRC patients (P = 0.032). Furthermore, we designed and transfected miR-592 mimics or inhibitors into the corresponding CRC lines, and our experiments in vitro demonstrated that miR-592 could promote cell proliferation, wound healing and invasion ability of CRC cells (P < 0.05), while miR-592 did not influence the CRC cell apoptosis (P > 0.05). All these results suggested that miR-592 functioned as a novel and potential carcinogen-initiated and metastasis-related biomarker in CRC, and down-regulation of miR-592 might be considered as a potentially significant molecular treatment strategy for CRC patients.
Keywords:miR-592  Colorectal cancer  Progression  Prognosis
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