Mo Ren, Peng Jingtao, Xiao Jiantao, Ma Jian, Li Weiguo, Wang Jing, Ruan Yuan, Ma Shaofei, Hong Yan, Wang Chenji, Gao Kun, Fan Jie
Department of Urology, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200080, China.
Department of Urology, Inner Mongolia Autonomous Region Peoples Hospital, Hohhot, 010017, Inner Mongolia, China.
Tumour Biol. 2016 Jul;37(7):9797-806. doi: 10.1007/s13277-016-4891-7. Epub 2016 Jan 26.
Clear cell renal cell carcinoma (ccRCC) is the most common primary kidney cancer in adults, and the identification of biomarkers involved in the pathogenesis and prognosis of ccRCC is crucial for early diagnosis and anticancer treatment. In this study, we demonstrate that thioredoxin domain-containing protein 5 (TXNDC5) expression is markedly upregulated in ccRCC tissues in comparison with adjacent non-cancerous tissues through quantitative RT-PCR, Western blotting, and immunohistochemical analyses. Importantly, TXNDC5 expression is negatively correlated with the overall survival of patients. Knockdown of TXNDC5 by siRNAs inhibits the cell growth, migration, and invasion of ccRCC cells as well as sensitizes ccRCC cells to chemotherapeutic drugs, such as Camptothecin and 5-Fluorouracil. Moreover, we used complementary DNA (cDNA) microarray analyses to explore the underlying molecular mechanisms of TXNDC5 in the pathogenesis of ccRCC. We demonstrate that knockdown of TXNDC5 affects the messenger RNA (mRNA) and protein levels of numerous important genes associated with tumorigenesis. In summary, our findings indicate that TXNDC5 performs an essential function in ccRCC pathogenesis and can serve as a novel prognostic marker of ccRCC.
透明细胞肾细胞癌（ccRCC）是成人中最常见的原发性肾癌，鉴定参与ccRCC发病机制和预后的生物标志物对于早期诊断和抗癌治疗至关重要。在本研究中，我们通过定量逆转录聚合酶链反应（RT-PCR）、蛋白质免疫印迹和免疫组织化学分析证明，与相邻的非癌组织相比，含硫氧还蛋白结构域蛋白5（TXNDC5）在ccRCC组织中的表达明显上调。重要的是，TXNDC5表达与患者的总生存期呈负相关。通过小干扰RNA（siRNA）敲低TXNDC5可抑制ccRCC细胞的生长、迁移和侵袭，并使ccRCC细胞对化疗药物如喜树碱和5-氟尿嘧啶敏感。此外，我们使用互补DNA（cDNA）微阵列分析来探索TXNDC5在ccRCC发病机制中的潜在分子机制。我们证明，敲低TXNDC5会影响许多与肿瘤发生相关的重要基因的信使核糖核酸（mRNA）和蛋白质水平。总之，我们的研究结果表明，TXNDC5在ccRCC发病机制中发挥着重要作用，可作为ccRCC的一种新的预后标志物。
