Bioinformatics analysis revealed hub genes and pathways involved in sorafenib resistance in hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is increasingly known as a serious, worldwide public health concern. Sorafenib resistance is the main challenge faced by many advanced HCC patients. The specific mechanisms of sorafenib resistance remind unclear. In the current study, GEO2R was conducted to identify di...
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| Format: | Article |
| Language: | English |
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AIMS Press
2019-07-01
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| Series: | Mathematical Biosciences and Engineering |
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| Online Access: | https://www.aimspress.com/article/10.3934/mbe.2019315?viewType=HTML |
| _version_ | 1811234581276262400 |
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| author | Jing Liu Wancheng Qiu Xiaoying Shen Guangchun Sun |
| author_facet | Jing Liu Wancheng Qiu Xiaoying Shen Guangchun Sun |
| author_sort | Jing Liu |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is increasingly known as a serious, worldwide public health concern. Sorafenib resistance is the main challenge faced by many advanced HCC patients. The specific mechanisms of sorafenib resistance remind unclear. In the current study, GEO2R was conducted to identify differentially expressed genes (DEGs) between sorafenib-resistant samples and the control group by using RNA-sequence analysis and analyzing dataset GSE109211. Next, protein-protein interaction (PPI) network was built to explore key targets proteins in sorafenib-resistant HCC. Furthermore, gene ontology (GO) analysis was used to research the underlying roles of key proteins. Moreover, the Kaplan-Meier survival analysis was performed to display the effect of key proteins on overall survival in HCC. Western blotting was performed to detected resistance-related proteins and CCK-8 assay was employed to measured cell viability. In the present research, 164 sorafenib resistance-related DEGs in HCC were identified by using RNA-sequence analysis and analyzing the dataset GSE109211. GO analysis revealed DEGs were involved in regulating multiple biological processes and molecular functions. DYNLL2, H2AFJ, SHANK2, ZWILCH, CDC14A, IFT20, MTA3, SERPINA1 and TCF4 were confirmed as key genes in this process. Moreover, our study showed Akt signaling was aberrantly activated and inhibition of Akt signaling enhanced anti-tumor capacity of sorafenib in sorafenib-resistant HCC cells. Identification of the DEGs in sorafenib resistant HCC cells may further provide the new insights of underlying sorafenib-resistant mechanisms and offer latent targets for early diagnosis and new therapies to improve clinical efficacy for sorafenib-resistant HCC patients. |
| first_indexed | 2024-04-12T11:39:57Z |
| format | Article |
| id | doaj.art-881aef56ea054093844f4048037c4dfb |
| institution | Directory Open Access Journal |
| issn | 1551-0018 |
| language | English |
| last_indexed | 2024-04-12T11:39:57Z |
| publishDate | 2019-07-01 |
| publisher | AIMS Press |
| record_format | Article |
| series | Mathematical Biosciences and Engineering |
| spelling | doaj.art-881aef56ea054093844f4048037c4dfb2022-12-22T03:34:43ZengAIMS PressMathematical Biosciences and Engineering1551-00182019-07-011666319633410.3934/mbe.2019315Bioinformatics analysis revealed hub genes and pathways involved in sorafenib resistance in hepatocellular carcinomaJing Liu0Wancheng Qiu1Xiaoying Shen2Guangchun Sun3Department of Pharmacy, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai 200240, ChinaDepartment of Pharmacy, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai 200240, ChinaDepartment of Pharmacy, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai 200240, ChinaDepartment of Pharmacy, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai 200240, ChinaHepatocellular carcinoma (HCC) is increasingly known as a serious, worldwide public health concern. Sorafenib resistance is the main challenge faced by many advanced HCC patients. The specific mechanisms of sorafenib resistance remind unclear. In the current study, GEO2R was conducted to identify differentially expressed genes (DEGs) between sorafenib-resistant samples and the control group by using RNA-sequence analysis and analyzing dataset GSE109211. Next, protein-protein interaction (PPI) network was built to explore key targets proteins in sorafenib-resistant HCC. Furthermore, gene ontology (GO) analysis was used to research the underlying roles of key proteins. Moreover, the Kaplan-Meier survival analysis was performed to display the effect of key proteins on overall survival in HCC. Western blotting was performed to detected resistance-related proteins and CCK-8 assay was employed to measured cell viability. In the present research, 164 sorafenib resistance-related DEGs in HCC were identified by using RNA-sequence analysis and analyzing the dataset GSE109211. GO analysis revealed DEGs were involved in regulating multiple biological processes and molecular functions. DYNLL2, H2AFJ, SHANK2, ZWILCH, CDC14A, IFT20, MTA3, SERPINA1 and TCF4 were confirmed as key genes in this process. Moreover, our study showed Akt signaling was aberrantly activated and inhibition of Akt signaling enhanced anti-tumor capacity of sorafenib in sorafenib-resistant HCC cells. Identification of the DEGs in sorafenib resistant HCC cells may further provide the new insights of underlying sorafenib-resistant mechanisms and offer latent targets for early diagnosis and new therapies to improve clinical efficacy for sorafenib-resistant HCC patients.https://www.aimspress.com/article/10.3934/mbe.2019315?viewType=HTMLbiomarkerssorafenib resistancegene expression profilingprognosisakt signaling |
| spellingShingle | Jing Liu Wancheng Qiu Xiaoying Shen Guangchun Sun Bioinformatics analysis revealed hub genes and pathways involved in sorafenib resistance in hepatocellular carcinoma Mathematical Biosciences and Engineering biomarkers sorafenib resistance gene expression profiling prognosis akt signaling |
| title | Bioinformatics analysis revealed hub genes and pathways involved in sorafenib resistance in hepatocellular carcinoma |
| title_full | Bioinformatics analysis revealed hub genes and pathways involved in sorafenib resistance in hepatocellular carcinoma |
| title_fullStr | Bioinformatics analysis revealed hub genes and pathways involved in sorafenib resistance in hepatocellular carcinoma |
| title_full_unstemmed | Bioinformatics analysis revealed hub genes and pathways involved in sorafenib resistance in hepatocellular carcinoma |
| title_short | Bioinformatics analysis revealed hub genes and pathways involved in sorafenib resistance in hepatocellular carcinoma |
| title_sort | bioinformatics analysis revealed hub genes and pathways involved in sorafenib resistance in hepatocellular carcinoma |
| topic | biomarkers sorafenib resistance gene expression profiling prognosis akt signaling |
| url | https://www.aimspress.com/article/10.3934/mbe.2019315?viewType=HTML |
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