Pan Yong, Zhang Yiru, Hu Xiaodan, Li Shibo
Department of Infectious Disease, Zhoushan Hospital, Wenzhou Medical University, 739 Dingshen Rd, Zhoushan City 316021, China.
State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou City 310003, China.
ACS Omega. 2023 Oct 3;8(41):38690-38703. doi: 10.1021/acsomega.3c06018. eCollection 2023 Oct 17.
The crucial role of competitive endogenous RNA (ceRNA) in the malignant biological behavior of tumors has been certificated. Nevertheless, the detailed function and molecular mechanism of ceRNA associated with cuproptosis in hepatocellular carcinoma (HCC) remains dismal. In this study, we first constructed a protein-protein interaction network and identified the module with the highest degree of aggregation degree. DLAT and PDHA1 were screened out of the module after differential expression and survival analysis. Next, we reverse-predicted the upstream miRNA and lncRNA from mRNA (DLAT, PDHA1) and successfully established the ceRNA network-SNHG3/miR-1306-5p/PDHA1. SNHG3 was identified to be an independent prognostic biomarker based on the outcome of univariate and multivariate Cox analyses. Subsequently, we implemented methylation, immune infiltration, and drug sensitivity analysis to investigate the potential biological functions of SNHG3 in HCC. In addition, SNHG3 expression was upregulated in liver cancer cell lines. In vitro functional assay revealed that SNHG3 knockdown significantly attenuated proliferation, migration, and invasion of liver cancer cells. In summary, SNHG3 exhibited oncogenic characterization via sponging miR-1306-5p to regulate PDHA1, which might function as a promising prognostic indicator and a potential therapeutic target for HCC and shed new light on the molecular mechanism of HCC progression.
竞争性内源性RNA（ceRNA）在肿瘤恶性生物学行为中的关键作用已得到证实。然而，ceRNA在肝细胞癌（HCC）中与铜死亡相关的详细功能和分子机制仍不清楚。在本研究中，我们首先构建了蛋白质-蛋白质相互作用网络，并确定了聚集度最高的模块。经过差异表达和生存分析，从该模块中筛选出DLAT和PDHA1。接下来，我们从mRNA（DLAT、PDHA1）反向预测上游miRNA和lncRNA，并成功建立了ceRNA网络-SNHG3/miR-1306-5p/PDHA1。基于单因素和多因素Cox分析结果，SNHG3被确定为一个独立的预后生物标志物。随后，我们进行了甲基化、免疫浸润和药物敏感性分析，以研究SNHG3在HCC中的潜在生物学功能。此外，SNHG3在肝癌细胞系中表达上调。体外功能试验表明，敲低SNHG3可显著减弱肝癌细胞的增殖、迁移和侵袭能力。总之，SNHG3通过海绵吸附miR-1306-5p来调节PDHA1，表现出致癌特性，这可能是HCC一个有前景的预后指标和潜在治疗靶点，并为HCC进展的分子机制提供了新的线索。
