Identification and validation of functional roles for three MYC-associated genes in hepatocellular carcinoma
Background: Aberrations in MYC underlie a large proportion of liver hepatocellular carcinoma (LIHC) cases; however, MYC is difficult to target because of its undruggable structure. We aimed to uncover MYC-associated molecular targets to provide new strategies for LIHC treatment. Methods: LIHC transc...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Journal of Advanced Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123223000231 |
| _version_ | 1797435801147015168 |
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| author | Sha Li Pei Xue Xun Diao Qi-Yu Fan Kun Ye Xiao-Mei Tang Jia Liu Zhong-Yan Huang Qing-Hai Tang Cheng-You Jia Rui Xin Zhong-Wei Lv Ji-Bin Liu Yu-Shui Ma Da Fu |
| author_facet | Sha Li Pei Xue Xun Diao Qi-Yu Fan Kun Ye Xiao-Mei Tang Jia Liu Zhong-Yan Huang Qing-Hai Tang Cheng-You Jia Rui Xin Zhong-Wei Lv Ji-Bin Liu Yu-Shui Ma Da Fu |
| author_sort | Sha Li |
| collection | DOAJ |
| description | Background: Aberrations in MYC underlie a large proportion of liver hepatocellular carcinoma (LIHC) cases; however, MYC is difficult to target because of its undruggable structure. We aimed to uncover MYC-associated molecular targets to provide new strategies for LIHC treatment. Methods: LIHC transcriptome datasets and clinical information were obtained from The Cancer Genome Atlas. A series of bioinformatics analyses were performed for 370 patients who were stratified based on the median MYC expression level (high-MYC group and low-MYC group). Correlation analysis was performed to determine relationships between the expression of key MYC-associated genes and prognosis, DNA promotor methylation, and immune cell infiltration. Gene ontology and Kyoto Encyclopedia of Genes and Genomes Pathway enrichment analyses were performed to elucidate the functions of these genes in LIHC. Their expression and functions in LIHC were further verified using transgenic mice overexpressing c-Myc under control of the hepatocyte-specific promoter (Alb-Cre). Results: AURKB, CCNB2, and CDKN3 were overexpressed in LIHC patients with high MYC expression and were associated with poor prognosis. Upregulation of these 3 genes was significantly correlated with hypomethylated promoter status, advanced T stage, metastasis, and immune cell infiltration in LIHC patients. Functional enrichment analyses indicated that these genes participate in the “p53 signaling pathway” and “cell cycle”. Furthermore, RT-PCR and IHC analysis revealed that their mRNA and protein expression levels were upregulated in an Alb-Cre;cMYClsl/- mouse model. Drugs that target these 3 MYC-related genes were identified. Conclusion: Taken together, our results identify biomarkers of potential utility for managing liver cancer therapy owing to their significance in tumorigenesis, proliferation, and tumor immunity. |
| first_indexed | 2024-03-09T10:53:19Z |
| format | Article |
| id | doaj.art-5b1dc4ef0d4d432f81b40b8b4b5c5ebe |
| institution | Directory Open Access Journal |
| issn | 2090-1232 |
| language | English |
| last_indexed | 2024-03-09T10:53:19Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Advanced Research |
| spelling | doaj.art-5b1dc4ef0d4d432f81b40b8b4b5c5ebe2023-12-01T05:01:20ZengElsevierJournal of Advanced Research2090-12322023-12-0154133146Identification and validation of functional roles for three MYC-associated genes in hepatocellular carcinomaSha Li0Pei Xue1Xun Diao2Qi-Yu Fan3Kun Ye4Xiao-Mei Tang5Jia Liu6Zhong-Yan Huang7Qing-Hai Tang8Cheng-You Jia9Rui Xin10Zhong-Wei Lv11Ji-Bin Liu12Yu-Shui Ma13Da Fu14Institute of Oncology, Affiliated Tumor Hospital of Nantong University, Nantong 226631, Jiangsu Province, China; Department of Head and Neck Surgery, Central Laboratory, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, ChinaDivision of Gastrointestinal and Colorectal Surgery, Ruijin Hospital, Department of General Surgery, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, ChinaInstitute of Oncology, Affiliated Tumor Hospital of Nantong University, Nantong 226631, Jiangsu Province, ChinaInstitute of Oncology, Affiliated Tumor Hospital of Nantong University, Nantong 226631, Jiangsu Province, ChinaDepartment of Urology, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China; Uro-Oncology Institute of Central South University, Changsha 410011, Hunan Province, ChinaGeneral Surgery, Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, ChinaGeneral Surgery, Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, ChinaGeneral Surgery, Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, ChinaHunan Key Laboratory for Conservation and Utilization of Biological Resources in the Nanyue Mountainous Region and College of Life Sciences and Environment, Hengyang Normal University, Hengyang 421008, Hunan Province, ChinaDepartment of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaInstitute of Oncology, Affiliated Tumor Hospital of Nantong University, Nantong 226631, Jiangsu Province, China; Corresponding authors.Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Corresponding authors.General Surgery, Institute of Pancreatic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; Corresponding authors.Background: Aberrations in MYC underlie a large proportion of liver hepatocellular carcinoma (LIHC) cases; however, MYC is difficult to target because of its undruggable structure. We aimed to uncover MYC-associated molecular targets to provide new strategies for LIHC treatment. Methods: LIHC transcriptome datasets and clinical information were obtained from The Cancer Genome Atlas. A series of bioinformatics analyses were performed for 370 patients who were stratified based on the median MYC expression level (high-MYC group and low-MYC group). Correlation analysis was performed to determine relationships between the expression of key MYC-associated genes and prognosis, DNA promotor methylation, and immune cell infiltration. Gene ontology and Kyoto Encyclopedia of Genes and Genomes Pathway enrichment analyses were performed to elucidate the functions of these genes in LIHC. Their expression and functions in LIHC were further verified using transgenic mice overexpressing c-Myc under control of the hepatocyte-specific promoter (Alb-Cre). Results: AURKB, CCNB2, and CDKN3 were overexpressed in LIHC patients with high MYC expression and were associated with poor prognosis. Upregulation of these 3 genes was significantly correlated with hypomethylated promoter status, advanced T stage, metastasis, and immune cell infiltration in LIHC patients. Functional enrichment analyses indicated that these genes participate in the “p53 signaling pathway” and “cell cycle”. Furthermore, RT-PCR and IHC analysis revealed that their mRNA and protein expression levels were upregulated in an Alb-Cre;cMYClsl/- mouse model. Drugs that target these 3 MYC-related genes were identified. Conclusion: Taken together, our results identify biomarkers of potential utility for managing liver cancer therapy owing to their significance in tumorigenesis, proliferation, and tumor immunity.http://www.sciencedirect.com/science/article/pii/S2090123223000231LIHCTumorTreatmentBiomarkerTherapy |
| spellingShingle | Sha Li Pei Xue Xun Diao Qi-Yu Fan Kun Ye Xiao-Mei Tang Jia Liu Zhong-Yan Huang Qing-Hai Tang Cheng-You Jia Rui Xin Zhong-Wei Lv Ji-Bin Liu Yu-Shui Ma Da Fu Identification and validation of functional roles for three MYC-associated genes in hepatocellular carcinoma Journal of Advanced Research LIHC Tumor Treatment Biomarker Therapy |
| title | Identification and validation of functional roles for three MYC-associated genes in hepatocellular carcinoma |
| title_full | Identification and validation of functional roles for three MYC-associated genes in hepatocellular carcinoma |
| title_fullStr | Identification and validation of functional roles for three MYC-associated genes in hepatocellular carcinoma |
| title_full_unstemmed | Identification and validation of functional roles for three MYC-associated genes in hepatocellular carcinoma |
| title_short | Identification and validation of functional roles for three MYC-associated genes in hepatocellular carcinoma |
| title_sort | identification and validation of functional roles for three myc associated genes in hepatocellular carcinoma |
| topic | LIHC Tumor Treatment Biomarker Therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2090123223000231 |
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