Gong Junhua, Cui Zheng, Li Li, Ma Qiang, Wang Qiufang, Gao Yinhe, Sun Hao
Health checkup Center, Beidaihe Sanatorium of Beijing Military Area Command, Chinese PLA, Qinhuangdao, 066000, People's Republic of China.
Tumour Biol. 2015 Sep;36(10):7831-40. doi: 10.1007/s13277-015-3510-3. Epub 2015 May 6.
Increasing evidence shows that abnormal microRNA (miRNA) expression is involved in tumorigenesis. MiR-25 was previously reported to act as tumor suppressor or oncogene in diverse cancers. However, their expression, function, and mechanism in gastric cancer (GC) are not well known. Here, we show that miR-25 was overexpressed in primary tumor tissues of GC patients and was significantly correlated with a more aggressive phenotype of GC in patients. MiR-25 inhibition significantly decreased the proliferation, invasion, and migration of GC cells in vitro. Furthermore, miR-25 repressed F-box and WD-40 domain protein 7 (FBXW7) expression by directly binding to 3-untranslated region (UTR) of FBXW7, and the inverse correlation was observed between the expressions of miR-25 and FBXW7 mRNA in primary GC tissues. Moreover, the restoration of FBXW7 led to suppressed proliferation, invasion, and migration of GC cells. In vivo, miR-25 promotes tumor growth of GC. Taken together, miR-25 promotes GC progression by directly downregulating FBXW7 expression and may be employed as a novel prognostic marker and therapeutic target of GC.
越来越多的证据表明,异常的微小RNA(miRNA)表达与肿瘤发生有关。先前有报道称,miR-25在多种癌症中可作为肿瘤抑制因子或癌基因发挥作用。然而,其在胃癌(GC)中的表达、功能及机制尚不清楚。在此,我们发现miR-25在GC患者的原发性肿瘤组织中过表达,且与患者GC更具侵袭性的表型显著相关。抑制miR-25可显著降低GC细胞在体外的增殖、侵袭和迁移能力。此外,miR-25通过直接结合F-box和WD-40结构域蛋白7(FBXW7)的3'-非翻译区(UTR)来抑制FBXW7的表达,并且在原发性GC组织中观察到miR-25与FBXW7 mRNA表达呈负相关。此外,恢复FBXW7的表达可导致GC细胞的增殖、侵袭和迁移受到抑制。在体内,miR-25促进GC的肿瘤生长。综上所述,miR-25通过直接下调FBXW7的表达促进GC进展,可能作为GC的一种新型预后标志物和治疗靶点。