Xu Zhipeng, Liu Min, Wang Jin, Liu Kai, Xu Liuyu, Fan Demin, Zhang Hui, Hu Wenxin, Wei Dan, Wang Jianning
Department of Urology, Shandong Qianfoshan Hospital, Cheeloo college of Medicine, Shandong University, Jinan, Shandong, China.
Department of Urology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong medicine and Health Key Laboratory of Organ Transplantation and Nephrosis, Shandong Institute of Nephrology, Jinan, China.
Cell Death Discov. 2022 Mar 22;8(1):125. doi: 10.1038/s41420-022-00933-6.
Clear cell renal cell carcinoma (ccRCC) is a serious threat to human health worldwide, while its heterogeneity limits therapeutic success and leads to poor survival outcomes. Single-cell RNA-sequencing (scRNA-seq) is an important technology, which provides deep insights into the genetic characteristics of carcinoma. In this study, we profiled the gene expression of single cells from human ccRCC tissues and adjacent normal tissues using the scRNA-seq. We found that MYH9 was commonly upregulated in the ccRCC cell subgroup. Additionally, MYH9 was of highly expression in ccRCC tissues and predicted poor prognosis of ccRCC patients. MYH9 knockdown in ccRCC cells dampened their proliferative and metastatic potentials, whereas MYH9 overexpression enhanced these properties. In vivo, MYH9 also promoted ccRCC growth. Mechanistic studies showed that MYH9 played these vital roles through AKT signaling pathway. Furthermore, MYH9/AKT axis determined the responses of ccRCC cells to sunitinib treatment and might serve as a biomarker for sunitinib benefits in ccRCC patients. Thus, MYH9 might be a novel therapeutic target and prognostic predictor for ccRCC.
透明细胞肾细胞癌（ccRCC）在全球范围内对人类健康构成严重威胁，其异质性限制了治疗效果并导致生存结局不佳。单细胞RNA测序（scRNA-seq）是一项重要技术，它能深入揭示癌症的遗传特征。在本研究中，我们使用scRNA-seq分析了来自人类ccRCC组织和相邻正常组织的单细胞基因表达。我们发现MYH9在ccRCC细胞亚群中普遍上调。此外，MYH9在ccRCC组织中高表达，并预示着ccRCC患者的预后不良。在ccRCC细胞中敲低MYH9会抑制其增殖和转移潜能，而MYH9过表达则增强这些特性。在体内，MYH9也促进ccRCC生长。机制研究表明，MYH9通过AKT信号通路发挥这些重要作用。此外，MYH9/AKT轴决定了ccRCC细胞对舒尼替尼治疗的反应，并可能作为ccRCC患者从舒尼替尼治疗中获益的生物标志物。因此，MYH9可能是ccRCC的一个新的治疗靶点和预后预测指标。
