Department of Pathology, CHA Bundang Medical Center, CHA University, 59 Yatap-rho, Bundang-gu, Seongnam-si, Gyeonggi-do 463-712, Republic of Korea; Institute for Clinical Research, CHA Bundang Medical Center, CHA University, 59 Yatap-rho, Bundang-gu, Seongnam-si, Gyeonggi-do 463-712, Republic of Korea.
Institute for Clinical Research, CHA Bundang Medical Center, CHA University, 59 Yatap-rho, Bundang-gu, Seongnam-si, Gyeonggi-do 463-712, Republic of Korea.
Cancer Lett. 2015 Jan 28;356(2 Pt B):937-45. doi: 10.1016/j.canlet.2014.11.011. Epub 2014 Nov 10.
MicroRNA-145 (miR-145) expression is downregulated in several human cancers, but its clinical and functional relevance to ovarian carcinoma has not yet been elucidated. This study addressed the hypothesis that miR-145 serves as a prognostic biomarker and a tumor suppressor that regulates the expression of high-mobility group A2 (HMGA2) oncoprotein in ovarian cancer. Here, we found that low miR-145 expression and HMGA2 overexpression determined by qRT-PCR and immunohistochemistry significantly correlated with advanced stage, lymph node involvement, and distant metastasis in 74 ovarian carcinomas. Low miR-145 expression significantly correlated with tumor recurrence and worse overall survival (HR=8.62, P = 0.039). Transfection of pre-miR-145 resulted in reduced cell growth and migration, and increased apoptosis of ovarian cancer cells by TUNEL, colony forming, and cell migration assays. MiR-145 was found to directly target HMGA2 by luciferase assay and Western blotting. Our findings suggest that miR-145 functions as a tumor suppressor in ovarian cancer and directly targets HMGA2 oncoprotein. Low miR-145 and high HMGA2 expressions are potential biomarkers of poor prognosis of ovarian carcinoma and miR-145 is the more powerful predictor of patient outcome.
miR-145(miR-145)在几种人类癌症中表达下调,但它与卵巢癌的临床和功能相关性尚未阐明。本研究旨在验证 miR-145 是否作为一种预后生物标志物和肿瘤抑制因子,调节卵巢癌中高迁移率族蛋白 A2(HMGA2)癌蛋白的表达。在这里,我们发现通过 qRT-PCR 和免疫组织化学检测到的低 miR-145 表达和 HMGA2 过表达与 74 例卵巢癌中的晚期、淋巴结受累和远处转移显著相关。低 miR-145 表达与肿瘤复发和总体生存不良显著相关(HR=8.62,P=0.039)。通过 TUNEL、集落形成和细胞迁移实验,转染 pre-miR-145 导致卵巢癌细胞的生长和迁移减少,凋亡增加。通过荧光素酶报告基因和 Western blot 检测发现 miR-145 可直接靶向 HMGA2。我们的研究结果表明,miR-145 在卵巢癌中作为一种肿瘤抑制因子发挥作用,并且直接靶向 HMGA2 癌蛋白。低 miR-145 和高 HMGA2 表达是卵巢癌不良预后的潜在生物标志物,miR-145 是患者预后的更有力预测指标。
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