Integrating bulk and single-cell RNA sequencing revealsSH3D21promotes hepatocellular carcinoma progression by activating the PI3K/AKT/mTOR pathway

Abstract

AbstractAs a novel genetic biomarker, the potential role ofSH3D21in hepatocellular carcinoma remains unclear. Here, we decipher the expression and function ofSH3D21in human hepatocellular carcinoma. The expression level and clinical significance ofSH3D21in hepatocellular carcinoma patients, the relationship betweenSH3D21and the features of tumor microenvironment (TME) and role ofSH3D21in 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 ofSH3D21on hepatocellular carcinoma cells were investigated by qRT-PCR, CCK-8 assay, colony forming assay and Western blot analysis. Bioinformatics analysis andin vitroexperiments revealed that the expression level ofSH3D21was up-regulated in hepatocellular carcinoma and correlated with the poor prognosis in hepatocellular carcinoma patients.SH3D21effectively promoted the proliferation, invasion, and migration as well as the formation of immunosuppressive microenvironment of hepatocellular carcinoma. In addition,SH3D21can activate the PI3K/AKT/mTOR signaling pathway.SH3D21stimulates the progression of hepatocellular carcinoma by activating the PI3K/AKT/mTOR signaling pathway, andSH3D21can serve as a prognostic biomarker and therapeutic target for hepatocellular carcinoma.