{"doi":"10.1177/1010428317695031","title":"Peroxisome proliferator-activated receptor gamma coactivator-1 alpha acts as a tumor suppressor in hepatocellular carcinoma","abstract":"<jats:p>Peroxisome proliferator-activated receptor gamma coactivator-1 alpha plays a crucial role in regulating the biosynthesis of mitochondria, which is closely linked to the energy metabolism in various tumors. This study investigated the regulatory role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha in the pathogenesis of hepatocellular carcinoma. In this study, the changes of peroxisome proliferator-activated receptor gamma coactivator-1 alpha messenger RNA levels between normal human liver and hepatocellular carcinoma tissue were examined by quantitative reverse transcription polymerase chain reaction. Knockdown of peroxisome proliferator-activated receptor gamma coactivator-1 alpha was conducted by RNA interference in the human liver cell line L02, while overexpression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha was conducted by adenovirus encoding peroxisome proliferator-activated receptor gamma coactivator-1 alpha complementary DNA in the human hepatocarcinoma cell line HepG2. Cellular morphological changes were observed via optical and electron microscopy. Cellular apoptosis was determined by Hoechst 33258 staining. In addition, the expression levels of 21,400 genes in tissues and cells were detected by microarray. It was shown that peroxisome proliferator-activated receptor gamma coactivator-1 alpha expression was significantly downregulated in hepatocellular carcinoma compared with normal liver tissues. After knockdown of peroxisome proliferator-activated receptor gamma coactivator-1 alpha expression in L02 cells, cells reverted to immature and dedifferentiated morphology exhibiting cancerous tendency. Apoptosis occurred in the HepG2 cells after transfection by adenovirus encoding peroxisome proliferator-activated receptor gamma coactivator-1 alpha. Microarray analysis showed consistent results. The results suggest that peroxisome proliferator-activated receptor gamma coactivator-1 alpha acts as a tumor suppressor in the formation and development of hepatocellular carcinoma and that peroxisome proliferator-activated receptor gamma coactivator-1 alpha may be a potential therapeutic target for hepatocellular carcinoma.</jats:p>","journal":"Tumor 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Zhang","orcid":"0000-0002-4835-8541","position":2,"is_corresponding":false},{"id":137177,"name":"Shuang Li","orcid":"0000-0001-7414-630X","position":3,"is_corresponding":false},{"id":70772,"name":"Xinyi Wang","orcid":"0000-0001-8003-4216","position":4,"is_corresponding":false},{"id":110979,"name":"Xia Wang","orcid":null,"position":5,"is_corresponding":false},{"id":144434,"name":"Cheng Wang","orcid":null,"position":6,"is_corresponding":false},{"id":15500,"name":"Bin Liu","orcid":"0000-0002-9113-9694","position":7,"is_corresponding":false},{"id":144435,"name":"Ke Zen","orcid":null,"position":8,"is_corresponding":false},{"id":144436,"name":"Chen-yu Zhang","orcid":null,"position":9,"is_corresponding":false},{"id":144437,"name":"Chunni Zhang","orcid":null,"position":10,"is_corresponding":false},{"id":144438,"name":"Yi Ba","orcid":null,"position":11,"is_corresponding":false},{"id":51524,"name":"Rui Liu","orcid":"0000-0002-4547-8695","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":3.4965075614664802,"endowment":3.4965075614664802,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28381162","pmcid":null,"openalex_id":"https://openalex.org/W2605340400","authors":[],"funders":[],"total_grants":0,"fwci":1.3455,"citation_percentile":0.80144185,"influential_citations":1,"citation_trend":[{"year":2018,"count":3},{"year":2019,"count":5},{"year":2020,"count":4},{"year":2021,"count":5},{"year":2022,"count":1},{"year":2023,"count":6},{"year":2024,"count":3},{"year":2025,"count":5}],"oa_status":"gold","license":"cc-by-nc","oa_locations":[{"url":"https://journals.sagepub.com/doi/pdf/10.1177/1010428317695031","host_type":"journal"},{"url":"https://journals.sagepub.com/doi/pdf/10.1177/1010428317695031","host_type":"GOLD"},{"url":"https://journals.sagepub.com/doi/pdf/10.1177/1010428317695031","host_type":"publisher"},{"url":"http://journals.sagepub.com/doi/pdf/10.1177/1010428317695031","host_type":"publisher"},{"url":"http://journals.sagepub.com/doi/full-xml/10.1177/1010428317695031","host_type":"publisher"},{"url":"https://doi.org/10.1177/1010428317695031","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28381162","host_type":"repository"},{"url":"https://doaj.org/article/1f3a2f6ce70c42279eb643c245d6349b","host_type":"repository"}],"fields_of_study":["Peroxisome Proliferator-Activated Receptors","Cancer, Hypoxia, and Metabolism","Quinazolinone synthesis and applications","Chemistry","Medicine","Adult","Aged","Apoptosis","Carcinoma, Hepatocellular","Female","Hep G2 Cells","Humans","Liver Neoplasms","Male","Middle Aged","Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha","RNA Interference","Transcriptome","Tumor Suppressor Proteins"],"mesh_terms":["Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha","Adult","Aged","Female","Carcinoma, Hepatocellular","Humans","Liver Neoplasms","Male","Middle Aged","Apoptosis","Tumor Suppressor Proteins","RNA Interference","Hep G2 Cells","Transcriptome"],"keywords":["Coactivator","Peroxisome proliferator-activated receptor","Peroxisome proliferator-activated receptor alpha","Gene knockdown","Biology","Nuclear receptor","Cancer research","Receptor","Molecular biology","Transcription factor","Apoptosis","Biochemistry","Gene","Mitochondria","Hepatocellular carcinoma","Microarray","carcinogenesis","Peroxisome Proliferator-activated Receptor Gamma Coactivator-1 Alpha"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-07T20:09:33.824060Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}