Ding Dexin, Zhang Yue, Wen Lin, Fu Jiangbo, Bai Xue, Fan Yuhua, Lin Yuan, Dai Hongshuang, Li Qiang, Zhang Yong, An Ruihua
Department of Urology, The First Affiliated Hospital of The Harbin Medical University, Harbin 150001, China.
Department of Urology, The Affiliated Tumor Hospital of The Harbin Medical University, Harbin 150001, China.
Oncotarget. 2017 Jun 27;8(38):63084-63095. doi: 10.18632/oncotarget.18647. eCollection 2017 Sep 8.
Clear-cell renal cell carcinoma (ccRCC) is an aggressive and malignant kidney cancer which has the worst prognosis. Although microRNAs (miRNAs) have recently been identified as a novel class of regulators in oncogenesis and metastasis, there are few studies on their participation in ccRCC. In the present study, we observed that miR-367 expression was increased in both human ccRCC tissues and cell lines. Cell proliferation was evaluated by MTT assay and 5-Ethynyl-2'-deoxyuridine (EdU) assay kit, which indicated that inhibition of miR-367 could suppress the ccRCC proliferation. Forced expression of miR-367 substantially induced cell migration and invasion evidenced by wound-healing and transwell assays, and this carcinogenesis could be abolished by miR-367 inhibitor treatment. Further analysis identified Metastasis-Associated Protein 3 (MTA3) as a direct target of miR-367. QRT-PCR and western blot results indicated the correlative expression of miR-367 and MTA3 in ccRCC tissue samples. Overexpression of MTA3 reversed miR-367-induced cell proliferation, migration and invasion. Our data uncovered a novel molecular interaction between miR-367 and MTA3, indicating a therapeutic strategy of miR-367 for ccRCC.
透明细胞肾细胞癌(ccRCC)是一种侵袭性恶性肾癌,预后最差。尽管微小RNA(miRNA)最近被确定为肿瘤发生和转移中的一类新型调节因子,但关于它们在ccRCC中的参与情况的研究很少。在本研究中,我们观察到miR-367在人ccRCC组织和细胞系中的表达均升高。通过MTT法和5-乙炔基-2'-脱氧尿苷(EdU)检测试剂盒评估细胞增殖,结果表明抑制miR-367可抑制ccRCC增殖。miR-367的强制表达通过伤口愈合和Transwell检测显著诱导细胞迁移和侵袭,而这种致癌作用可通过miR-367抑制剂处理消除。进一步分析确定转移相关蛋白3(MTA3)是miR-367的直接靶点。QRT-PCR和western blot结果表明miR-367和MTA3在ccRCC组织样本中的相关表达。MTA3的过表达逆转了miR-367诱导的细胞增殖、迁移和侵袭。我们的数据揭示了miR-367与MTA3之间一种新的分子相互作用,表明了miR-367对ccRCC的一种治疗策略。