Integrating bulk and single-cell RNA sequencing reveals SH3D21 promotes hepatocellular carcinoma progression by activating the PI3K/AKT/mTOR pathway
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 relati...
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| Published in | PloS one Vol. 20; no. 4; p. e0302766 |
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| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
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Public Library of Science
03.04.2025
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| Abstract | 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. |
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| AbstractList | 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.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. 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. 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. |
| Audience | Academic |
| Author | Liu, Li Tong, Wangxia Qin, Na Luo, Ning Liu, Rong Lu, Tao Chen, Jibing |
| AuthorAffiliation | 1 Department of Hepatology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China 3 Department of hepatobiliary surgery, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China King Faisal Specialist Hospital and Research Center, Saudi Arabia 4 Centre for Translational Medical Research in Integrative Chinese and Western Medicine, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China 2 The Graduate School of Guangxi University of Chinese Medicine, Nanning, Guangxi, China 5 Department of Neurology, RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China |
| AuthorAffiliation_xml | – name: 5 Department of Neurology, RuiKang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China – name: 2 The Graduate School of Guangxi University of Chinese Medicine, Nanning, Guangxi, China – name: 4 Centre for Translational Medical Research in Integrative Chinese and Western Medicine, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China – name: 3 Department of hepatobiliary surgery, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China – name: King Faisal Specialist Hospital and Research Center, Saudi Arabia – name: 1 Department of Hepatology, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, China |
| Author_xml | – sequence: 1 givenname: Wangxia surname: Tong fullname: Tong, Wangxia – sequence: 2 givenname: Na surname: Qin fullname: Qin, Na – sequence: 3 givenname: Tao surname: Lu fullname: Lu, Tao – sequence: 4 givenname: Li surname: Liu fullname: Liu, Li – sequence: 5 givenname: Rong surname: Liu fullname: Liu, Rong – sequence: 6 givenname: Jibing surname: Chen fullname: Chen, Jibing – sequence: 7 givenname: Ning orcidid: 0000-0002-3892-524X surname: Luo fullname: Luo, Ning |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/40179068$$D View this record in MEDLINE/PubMed |
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| Copyright | Copyright: © 2025 Tong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. COPYRIGHT 2025 Public Library of Science 2025 Tong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2025 Tong et al 2025 Tong et al 2025 Tong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
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| Snippet | As a novel genetic biomarker, the potential role of SH3D21 in hepatocellular carcinoma remains unclear. Here, we decipher the expression and function of SH3D21... As a novel genetic biomarker, the potential role of SH3D21 in hepatocellular carcinoma remains unclear. Here, we decipher the expression and function of SH3D21... |
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| SubjectTerms | 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 |
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| Title | Integrating bulk and single-cell RNA sequencing reveals SH3D21 promotes hepatocellular carcinoma progression by activating the PI3K/AKT/mTOR pathway |
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