Shi Liping, Xiao Long, Heng Baoli, Mo Shijie, Chen Weijun, Su Zexuan
Department of Urology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, Guangdong, China.
Int Urol Nephrol. 2017 Jul;49(7):1165-1176. doi: 10.1007/s11255-017-1578-y. Epub 2017 Mar 27.
Placenta specific 8 (PLAC8) plays an important role in many different cellular processes and human diseases, including multiple types of cancer. However, the functional role of PLAC8 in clear cell renal cell carcinoma (ccRCC) has never been elucidated.
PLAC8 mRNA expression was investigated in 31 pairs of fresh ccRCC tumor tissues and matched adjacent non-tumor tissues by RT-qPCR and confirmed by analyzing the TCGA KRCC dataset which contains RNA-seq data of 534 ccRCC and 72 solid normal tissues. Protein level of PLAC8 expression was also investigated using immunohistochemistry in 129 ccRCC samples. Correlations with clinicopathological factors and overall survival were analyzed. To examine its effect on the biological activity, PLAC8 siRNAs were transfected into ccRCC cells. Cell proliferation was assessed by CCK8 cell viability assays, clone formation assays, and EdU incorporation assays. Cell invasion was examined using transwell assays. RNA sequencing was then performed to further elucidate the mechanisms by which PLAC8 regulates the cancer.
PLAC8 expression was positively correlated with tumor size, metastasis, and clinical stage of ccRCC. Additionally, high PLAC8 expression was closely associated with a shorter overall survival time. Knockdown of PLAC8 with siRNAs significantly reduced the proliferation and invasion of RCC cells and increased the sensitivity of RCC cells to cisplatin. RNA-seq analysis revealed that knockdown of PLAC8 down-regulated the expression of a panel of inflammatory mediators, which suggested that PLAC8 is associated with the ccRCC inflammatory microenvironment. Patients with high expression of PLAC8 had a significantly higher number of infiltrative lymphocytes than patients with low expression of PLAC8.
Our findings suggest that PLAC8 may be a potential prognostic indicator and therapeutic target for ccRCC.
胎盘特异性8（PLAC8）在许多不同的细胞过程和人类疾病中发挥重要作用，包括多种类型的癌症。然而，PLAC8在透明细胞肾细胞癌（ccRCC）中的功能作用尚未阐明。
通过RT-qPCR在31对新鲜ccRCC肿瘤组织和匹配的相邻非肿瘤组织中研究PLAC8 mRNA表达，并通过分析包含534例ccRCC和72例实体正常组织RNA测序数据的TCGA-KRCC数据集进行确认。还使用免疫组织化学在129例ccRCC样本中研究PLAC8表达的蛋白水平。分析其与临床病理因素和总生存期的相关性。为了研究其对生物学活性的影响，将PLAC8 siRNA转染到ccRCC细胞中。通过CCK8细胞活力测定、克隆形成测定和EdU掺入测定评估细胞增殖。使用Transwell测定检查细胞侵袭。然后进行RNA测序以进一步阐明PLAC8调节癌症的机制。
PLAC8表达与ccRCC的肿瘤大小、转移和临床分期呈正相关。此外，高PLAC8表达与较短的总生存时间密切相关。用siRNA敲低PLAC8可显著降低RCC细胞的增殖和侵袭，并增加RCC细胞对顺铂的敏感性。RNA测序分析显示，敲低PLAC8可下调一组炎症介质的表达，这表明PLAC8与ccRCC炎症微环境相关。PLAC8高表达患者的浸润淋巴细胞数量明显高于PLAC8低表达患者。
我们的研究结果表明，PLAC8可能是ccRCC的潜在预后指标和治疗靶点。
