Wu Xin-Lin, Yang Zhi-Wen, He Li, Dong Pei-De, Hou Ming-Xing, Meng Xing-Kai, Zhao Hai-Ping, Wang Zhao-Yang, Wang Feng, Jia Yong-Feng, Shi Lin
Department of Gastrointestinal Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010059, Inner Mongolian Autonomous Region, China.
Department of Hepatobiliary Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010059, Inner Mongolian Autonomous Region, China.
Oncotarget. 2017 Sep 15;8(47):82968-82980. doi: 10.18632/oncotarget.20897. eCollection 2017 Oct 10.
Colorectal cancer (CRC) is one of the most common malignancies worldwide. Ribosome biogenesis regulatory protein homolog (RRS1) is an essential factor involved in ribosome biogenesis, while its role in CRC remains largely unclear. Here, we found that RRS1 expression was significantly higher in CRC tissues compared with adjacent normal tissues. RRS1 High expression also predicted poor overall survival of CRC patients. Knockdown of RRS1 induced the G2/M cell cycle arrest, apoptosis and suppressed the proliferation of RKO and HCT-116 CRC cells. Furthermore, angiogenesis was also reduced in CRC cells after RRS1 knockdown. In addition, suppression of RRS1 blunted the tumor formation of CRC cells in nude mice. At the molecular level, silencing of RRS1 decreased the expression of M-phase inducer phosphatase 3 (CDC25C), Cyclin-dependent kinase 1 (CDK1), antigen KI-67 (KI67) and increased the protein level of cyclin-dependent kinase inhibitor 1 (CDKN1A) and tumor suppressor p53 (p53). Taken together, our findings provide evidence that RRS1 may promote the development of colon cancer. Therefore, targeting RRS1 may be a promising therapeutic strategy for CRC patients.
结直肠癌（CRC）是全球最常见的恶性肿瘤之一。核糖体生物合成调节蛋白同源物（RRS1）是参与核糖体生物合成的一个重要因素，但其在结直肠癌中的作用仍不清楚。在此，我们发现与相邻正常组织相比，RRS1在结直肠癌组织中的表达显著更高。RRS1高表达还预示着结直肠癌患者总体生存率较差。敲低RRS1可诱导G2/M期细胞周期阻滞、细胞凋亡，并抑制RKO和HCT-116结直肠癌细胞的增殖。此外，敲低RRS1后，结直肠癌细胞中的血管生成也减少。另外，抑制RRS1可减弱结直肠癌细胞在裸鼠体内的肿瘤形成。在分子水平上，沉默RRS1可降低M期诱导磷酸酶3（CDC25C）、细胞周期蛋白依赖性激酶1（CDK1）、抗原KI-67（KI67）的表达，并增加细胞周期蛋白依赖性激酶抑制剂1（CDKN1A）和肿瘤抑制因子p53（p53）的蛋白水平。综上所述，我们的研究结果表明RRS1可能促进结肠癌的发展。因此，靶向RRS1可能是一种有前景的针对结直肠癌患者的治疗策略。
