Yamada Yasutaka, Arai Takayuki, Kojima Satoko, Sugawara Sho, Kato Mayuko, Okato Atsushi, Yamazaki Kazuto, Naya Yukio, Ichikawa Tomohiko, Seki Naohiko
Department of Functional Genomics, Chiba University Graduate School of Medicine, Chiba, Japan.
Department of Urology, Chiba University Graduate School of Medicine, Chiba, Japan.
Oncotarget. 2018 Jun 1;9(42):26638-26658. doi: 10.18632/oncotarget.25410.
Recent studies revealed that some passenger strands of miRNAs acted as anti-tumor or oncogenic miRNAs in cancer cells. In this study, we focused on (the passenger strand) and (the guide strand) based on microRNA (miRNA) expression signatures of cancer cells. Both and were downregulated in renal cell carcinoma (RCC) tissues and low expression of these miRNAs was significantly associated with poor prognosis. Cancer cell proliferation, migration and invasive abilities were significantly inhibited by ectopic expression of and . To identify their oncogenic targets, we applied a combination of genome-wide gene expression and miRNA database analyses. We focused on spindle and kinetochore-associated proteins, and and demonstrated direct regulation of by and by in RCC cells. Our present data demonstrated overexpression of in RCC clinical specimens. Moreover, the study showed that the / axis contributed to cancer cell aggressiveness. Analytic strategies based on anti-tumor miRNAs, including passenger strands of miRNAs, are effective approaches for the elucidation of the molecular pathogenesis of RCC.
最近的研究表明,一些miRNA的过客链在癌细胞中充当抗肿瘤或致癌miRNA。在本研究中,我们基于癌细胞的微小RNA(miRNA)表达特征,重点研究了(过客链)和(引导链)。二者在肾细胞癌(RCC)组织中均下调,且这些miRNA的低表达与不良预后显著相关。异位表达和可显著抑制癌细胞的增殖、迁移和侵袭能力。为了鉴定它们的致癌靶点,我们联合应用了全基因组基因表达分析和miRNA数据库分析。我们聚焦于纺锤体和动粒相关蛋白、和,并证明了在RCC细胞中可直接调控,可直接调控。我们目前的数据表明在RCC临床标本中过表达。此外,该研究表明/轴促成了癌细胞的侵袭性。基于抗肿瘤miRNA(包括miRNA的过客链)的分析策略是阐明RCC分子发病机制的有效方法。