Shang Yuanyuan, Zhang Fang, Li Dehui, Li Chang, Li Hongbo, Jiang Yingjian, Zhang Dianliang
Center of Colon and Rectum, Qingdao Municipal Hospital, Qingdao University, Qingdao 266011, Shandong Province, China.
Department of Pathology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266011, Shandong Province, China.
Pathol Res Pract. 2018 Oct;214(10):1613-1620. doi: 10.1016/j.prp.2018.08.012. Epub 2018 Aug 11.
Ubiquinol-cytochrome c reductase complex core protein 2 (UQCRC2) is an important subunit of mitochondrial respiratory complex III. However, its role in tumorigenesis and tumor progression remains unknown, especially with regards to colorectal cancer (CRC). In this research, we measured the expression of UQCRC2 protein by immunohistochemistry assay in 89 paired paraffin-embedded tumor tissues and corresponding adjacent normal tissues from patients with colorectal adenocarcinoma and investigated possible correlations of UQCRC2 expression with clinicopathological parameters and prognosis. We found that UQCRC2 was significantly upregulated in CRC tissues compared with adjacent normal tissues, and immunohistochemical UQCRC2 status was correlated to the depth of invasion (T), lymph node metastasis (N), advanced TNM stage. Multivariate analysis indicated that UQCRC2 remained an independent prognostic factor for poorer overall survival. Furthermore, we determined the role of UQCRC2-knockdown in CRC cells (RKO and HCT116) using lentivirus-mediated small hairpin RNAs (shRNAs). The effects of UQCRC2 knockdown on CRC cells (RKO and HCT116) proliferation were analyzed by cell proliferation and colony formation assay, and cell cycle and apoptosis were assessed by flow cytometry. We found that silencing UQCRC2 suppressed cell proliferation and colony formation in RKO and HCT116 cells, led to a cell cycle arrest and induced cell apoptosis in vitro. These results provided novel insights into the potential role of UQCRC2 in the tumorigenesis and progression of CRC, and revealed that UQCRC2 may serve as a new prognostic and therapeutic target in CRC.
泛醇 - 细胞色素c还原酶复合体核心蛋白2（UQCRC2）是线粒体呼吸复合体III的一个重要亚基。然而，其在肿瘤发生和肿瘤进展中的作用尚不清楚，尤其是在结直肠癌（CRC）方面。在本研究中，我们通过免疫组织化学分析测定了89对来自大肠腺癌患者的石蜡包埋肿瘤组织及相应癌旁正常组织中UQCRC2蛋白的表达，并研究了UQCRC2表达与临床病理参数及预后之间的可能相关性。我们发现，与癌旁正常组织相比，CRC组织中UQCRC2显著上调，且免疫组织化学检测的UQCRC2状态与浸润深度（T）、淋巴结转移（N）、TNM分期相关。多因素分析表明，UQCRC2仍然是总体生存率较差的独立预后因素。此外，我们使用慢病毒介导的小发夹RNA（shRNAs）确定了UQCRC2敲低在CRC细胞（RKO和HCT116）中的作用。通过细胞增殖和集落形成试验分析了UQCRC2敲低对CRC细胞（RKO和HCT116）增殖的影响，并通过流式细胞术评估细胞周期和细胞凋亡。我们发现，沉默UQCRC2可抑制RKO和HCT116细胞的增殖和集落形成，导致细胞周期停滞并在体外诱导细胞凋亡。这些结果为UQCRC2在CRC发生和进展中的潜在作用提供了新的见解，并表明UQCRC2可能作为CRC的一个新的预后和治疗靶点。
