Integrating bulk and single-cell RNA sequencing reveals SH3D21 promotes hepatocellular carcinoma progression by activating the PI3K/AKT/mTOR pathway

• Published in: PloS one Vol. 20; no. 4; p. e0302766
• Main Authors: Tong, Wangxia, Qin, Na, Lu, Tao, Liu, Li, Liu, Rong, Chen, Jibing, Luo, Ning
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.04.2025; Public Library of Science (PLoS)
• Subjects: 1-Phosphatidylinositol 3-kinase; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; AKT protein; Analysis; Bioinformatics; Biological effects; Biology and Life Sciences; Biomarkers; Biomarkers, Tumor - genetics; Cancer; Cancer therapies; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Cell cycle; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Chemotherapy; Cholecystokinin; Datasets; Development and progression; Disease Progression; Female; Gene expression; Gene Expression Regulation, Neoplastic; Gene sequencing; Genes; Genetic aspects; Genomes; Genomics; Health aspects; Hepatocellular carcinoma; Hepatoma; Humans; Immunotherapy; Kinases; Liver cancer; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Male; Medical prognosis; Medicine and Health Sciences; Membrane proteins; Metabolism; Oncology, Experimental; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Prognosis; Protein kinases; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Quality control; RNA; RNA sequencing; Sequence Analysis, RNA; Signal Transduction; Single-Cell Analysis; Software; Therapeutic targets; TOR protein; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism; Traditional Chinese medicine; Tumor microenvironment; Tumor Microenvironment - genetics; Tumors; China; United States; Massachusetts; Illinois; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0302766

As a novel genetic biomarker, the potential role of SH3D21 in hepatocellular carcinoma remains unclear. Here, we decipher the expression and function of SH3D21 in human hepatocellular carcinoma. The expression level and clinical significance of SH3D21 in hepatocellular carcinoma patients, the relationship between SH3D21 and the features of tumor microenvironment (TME) and role of SH3D21 in promoting hepatocellular carcinoma progression were analyzed based on the bulk samples obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Single-cell sequencing samples from Gene Expression Omnibus (GEO) database were employed to verify the prediction mechanism. Additionally, different biological effects of SH3D21 on hepatocellular carcinoma cells were investigated by qRT-PCR, CCK-8 assay, colony forming assay and Western blot analysis. Bioinformatics analysis and in vitro experiments revealed that the expression level of SH3D21 was up-regulated in hepatocellular carcinoma and correlated with the poor prognosis in hepatocellular carcinoma patients. SH3D21 effectively promoted the proliferation, invasion, and migration as well as the formation of immunosuppressive microenvironment of hepatocellular carcinoma. In addition, SH3D21 can activate the PI3K/AKT/mTOR signaling pathway. SH3D21 stimulates the progression of hepatocellular carcinoma by activating the PI3K/AKT/mTOR signaling pathway, and SH3D21 can serve as a prognostic biomarker and therapeutic target for hepatocellular carcinoma.