Wang Junqing, Hao Fengjie, Fei Xiaochun, Chen Yongjun
Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine 197 Rui Jin Er Road, Shanghai 200025, People's Republic of China.
Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine 197 Rui Jin Er Road, Shanghai 200025, People's Republic of China.
Am J Transl Res. 2019 Nov 15;11(11):6924-6937. eCollection 2019.
Patients diagnosed with hepatocellular carcinoma (HCC) suffered a high risk of recurrence and poor prognosis. Identification of differentially expressed genes (DEGs) in HCC provides potential biomarkers for evaluating prognosis and specific therapeutic treatments. In this study, DEGs over-expressed in HCC specimens with a fold change over 2.0 were collected through integrative bioinformatics analysis from GEO datasets. Gene ontology and KEGG pathway enrichment were conducted by applying DAVID database. We noticed Secreted phosphoprotein 1 (SPP1) as one of the signature genes up-regulated in HCC tissues with a close relation to the tumor process. Eighty-seven paired HCC specimens from our medical center were explored to verify the aberrant expression of SPP1 by IHC and qRT-PCR assay. Depletion of SPP1 in HCC Hep3B cells was established. The cell proliferation was impaired in SPP1 depleted cells, along with a resistance of cell apoptosis by down-regulating SPP1. Intriguingly, we further validated a direct interaction between miR-181c and SPP1, which indicated a post-transcriptional regulation mechanism of SPP1 in HCC. Thus, our results suggest that SPP1 may function as an enhancer of HCC growth targeted by miR-181c, and probably provide us an innovational target for HCC diagnose and therapeutic treatment.
被诊断为肝细胞癌(HCC)的患者复发风险高且预后不良。鉴定HCC中差异表达基因(DEGs)可为评估预后和特定治疗提供潜在的生物标志物。在本研究中,通过对GEO数据集进行综合生物信息学分析,收集了HCC标本中上调倍数超过2.0的DEGs。利用DAVID数据库进行基因本体论和KEGG通路富集分析。我们发现分泌磷蛋白1(SPP1)是HCC组织中上调的标志性基因之一,与肿瘤进程密切相关。本研究利用医学中心的87对HCC标本,通过免疫组化(IHC)和qRT-PCR检测验证SPP1的异常表达。建立了HCC Hep3B细胞中SPP1缺失模型。SPP1缺失的细胞增殖受到抑制,同时下调SPP1可使细胞凋亡抗性增强。有趣的是,我们进一步验证了miR-181c与SPP1之间的直接相互作用,这表明SPP1在HCC中存在转录后调控机制。因此,我们的研究结果表明,SPP1可能作为miR-181c靶向的HCC生长增强因子,可能为HCC的诊断和治疗提供新的靶点。