A Novel mRNA-miRNA Regulatory Sub-Network Associated With Prognosis of Metastatic Clear Cell Renal Cell Carcinoma
BackgroundClear cell renal cell carcinoma (ccRCC) is a urinary disease with high incidence. The high incidence of metastasis is the leading cause of death in patients with ccRCC. This study was aimed to identify the gene signatures during the metastasis of ccRCC.MethodsTwo datasets, including one ge...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-01-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2020.593601/full |
| _version_ | 1818428865064730624 |
|---|---|
| author | Tianyu Yang Xiaofen Miao Zhanxiang Bai Jian Tu Shanshan Shen Hui Niu Wei Xia Juan Wang Yongsheng Zhang |
| author_facet | Tianyu Yang Xiaofen Miao Zhanxiang Bai Jian Tu Shanshan Shen Hui Niu Wei Xia Juan Wang Yongsheng Zhang |
| author_sort | Tianyu Yang |
| collection | DOAJ |
| description | BackgroundClear cell renal cell carcinoma (ccRCC) is a urinary disease with high incidence. The high incidence of metastasis is the leading cause of death in patients with ccRCC. This study was aimed to identify the gene signatures during the metastasis of ccRCC.MethodsTwo datasets, including one gene expression profile dataset and one microRNA (miRNA) expression profile dataset, were downloaded from Gene Expression Omnibus (GEO) database. The integrated bioinformatics analysis was performed using the (limma) R package, miRWalk, DAVID, STRING, Kaplan-Meier plotter databases. Quantitative real-time polymerase chain reaction (qPCR) was conducted to validate the expression of differentially expressed genes (DEGs) and DE-miRNAs.ResultsIn total, 84 DEGs (68 up-regulated and 16 down-regulated) and 41 DE-miRNAs (24 up-regulated and 17 down-regulated) were screened from GSE22541 and GSE37989 datasets, respectively. Furthermore, 11 hub genes and 3 key miRNAs were identified from the PPI network, including FBLN1, THBS2, SCGB1A1, NKX2-1, COL11A1, DCN, LUM, COL1A1, COL6A3, SFTPC, SFTPB, miR-328, miR-502, and miR-504. The qPCR data showed that most of the selected genes and miRNAs were consistent with that in our integrated analysis. A novel mRNA-miRNA network, SFTPB-miR-328-miR-502-miR-504-NKX2-1 was found in metastatic ccRCC after the combination of data from expression, survival analysis, and experiment validation.ConclusionIn conclusion, key candidate genes and miRNAs were identified and a novel mRNA-miRNA network was constructed in ccRCC metastasis using integrated bioinformatics analysis and qPCR validation, which might be utilized as diagnostic biomarkers and molecular targets of metastatic ccRCC. |
| first_indexed | 2024-12-14T15:08:24Z |
| format | Article |
| id | doaj.art-ff5a729ac8244f4f83829c40b6fb6c18 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-14T15:08:24Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-ff5a729ac8244f4f83829c40b6fb6c182022-12-21T22:56:38ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-01-011010.3389/fonc.2020.593601593601A Novel mRNA-miRNA Regulatory Sub-Network Associated With Prognosis of Metastatic Clear Cell Renal Cell CarcinomaTianyu Yang0Xiaofen Miao1Zhanxiang Bai2Jian Tu3Shanshan Shen4Hui Niu5Wei Xia6Juan Wang7Yongsheng Zhang8Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Pathology, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, ChinaDepartment of Pathology, The People’s hospital of Hainan Tibetan Autonomous Prefecture, Qinghai, ChinaDepartment of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou, ChinaDepartment of Pathology, Wuzhong People’s Hospital of Suzhou, Suzhou, ChinaDepartment of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou, ChinaBackgroundClear cell renal cell carcinoma (ccRCC) is a urinary disease with high incidence. The high incidence of metastasis is the leading cause of death in patients with ccRCC. This study was aimed to identify the gene signatures during the metastasis of ccRCC.MethodsTwo datasets, including one gene expression profile dataset and one microRNA (miRNA) expression profile dataset, were downloaded from Gene Expression Omnibus (GEO) database. The integrated bioinformatics analysis was performed using the (limma) R package, miRWalk, DAVID, STRING, Kaplan-Meier plotter databases. Quantitative real-time polymerase chain reaction (qPCR) was conducted to validate the expression of differentially expressed genes (DEGs) and DE-miRNAs.ResultsIn total, 84 DEGs (68 up-regulated and 16 down-regulated) and 41 DE-miRNAs (24 up-regulated and 17 down-regulated) were screened from GSE22541 and GSE37989 datasets, respectively. Furthermore, 11 hub genes and 3 key miRNAs were identified from the PPI network, including FBLN1, THBS2, SCGB1A1, NKX2-1, COL11A1, DCN, LUM, COL1A1, COL6A3, SFTPC, SFTPB, miR-328, miR-502, and miR-504. The qPCR data showed that most of the selected genes and miRNAs were consistent with that in our integrated analysis. A novel mRNA-miRNA network, SFTPB-miR-328-miR-502-miR-504-NKX2-1 was found in metastatic ccRCC after the combination of data from expression, survival analysis, and experiment validation.ConclusionIn conclusion, key candidate genes and miRNAs were identified and a novel mRNA-miRNA network was constructed in ccRCC metastasis using integrated bioinformatics analysis and qPCR validation, which might be utilized as diagnostic biomarkers and molecular targets of metastatic ccRCC.https://www.frontiersin.org/articles/10.3389/fonc.2020.593601/fullclear cell renal cell carcinomacancer metastasisbioinformatics analysishub genesmiRNAs |
| spellingShingle | Tianyu Yang Xiaofen Miao Zhanxiang Bai Jian Tu Shanshan Shen Hui Niu Wei Xia Juan Wang Yongsheng Zhang A Novel mRNA-miRNA Regulatory Sub-Network Associated With Prognosis of Metastatic Clear Cell Renal Cell Carcinoma Frontiers in Oncology clear cell renal cell carcinoma cancer metastasis bioinformatics analysis hub genes miRNAs |
| title | A Novel mRNA-miRNA Regulatory Sub-Network Associated With Prognosis of Metastatic Clear Cell Renal Cell Carcinoma |
| title_full | A Novel mRNA-miRNA Regulatory Sub-Network Associated With Prognosis of Metastatic Clear Cell Renal Cell Carcinoma |
| title_fullStr | A Novel mRNA-miRNA Regulatory Sub-Network Associated With Prognosis of Metastatic Clear Cell Renal Cell Carcinoma |
| title_full_unstemmed | A Novel mRNA-miRNA Regulatory Sub-Network Associated With Prognosis of Metastatic Clear Cell Renal Cell Carcinoma |
| title_short | A Novel mRNA-miRNA Regulatory Sub-Network Associated With Prognosis of Metastatic Clear Cell Renal Cell Carcinoma |
| title_sort | novel mrna mirna regulatory sub network associated with prognosis of metastatic clear cell renal cell carcinoma |
| topic | clear cell renal cell carcinoma cancer metastasis bioinformatics analysis hub genes miRNAs |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2020.593601/full |
| work_keys_str_mv | AT tianyuyang anovelmrnamirnaregulatorysubnetworkassociatedwithprognosisofmetastaticclearcellrenalcellcarcinoma AT xiaofenmiao anovelmrnamirnaregulatorysubnetworkassociatedwithprognosisofmetastaticclearcellrenalcellcarcinoma AT zhanxiangbai anovelmrnamirnaregulatorysubnetworkassociatedwithprognosisofmetastaticclearcellrenalcellcarcinoma AT jiantu anovelmrnamirnaregulatorysubnetworkassociatedwithprognosisofmetastaticclearcellrenalcellcarcinoma AT shanshanshen anovelmrnamirnaregulatorysubnetworkassociatedwithprognosisofmetastaticclearcellrenalcellcarcinoma AT huiniu anovelmrnamirnaregulatorysubnetworkassociatedwithprognosisofmetastaticclearcellrenalcellcarcinoma AT weixia anovelmrnamirnaregulatorysubnetworkassociatedwithprognosisofmetastaticclearcellrenalcellcarcinoma AT juanwang anovelmrnamirnaregulatorysubnetworkassociatedwithprognosisofmetastaticclearcellrenalcellcarcinoma AT yongshengzhang anovelmrnamirnaregulatorysubnetworkassociatedwithprognosisofmetastaticclearcellrenalcellcarcinoma AT tianyuyang novelmrnamirnaregulatorysubnetworkassociatedwithprognosisofmetastaticclearcellrenalcellcarcinoma AT xiaofenmiao novelmrnamirnaregulatorysubnetworkassociatedwithprognosisofmetastaticclearcellrenalcellcarcinoma AT zhanxiangbai novelmrnamirnaregulatorysubnetworkassociatedwithprognosisofmetastaticclearcellrenalcellcarcinoma AT jiantu novelmrnamirnaregulatorysubnetworkassociatedwithprognosisofmetastaticclearcellrenalcellcarcinoma AT shanshanshen novelmrnamirnaregulatorysubnetworkassociatedwithprognosisofmetastaticclearcellrenalcellcarcinoma AT huiniu novelmrnamirnaregulatorysubnetworkassociatedwithprognosisofmetastaticclearcellrenalcellcarcinoma AT weixia novelmrnamirnaregulatorysubnetworkassociatedwithprognosisofmetastaticclearcellrenalcellcarcinoma AT juanwang novelmrnamirnaregulatorysubnetworkassociatedwithprognosisofmetastaticclearcellrenalcellcarcinoma AT yongshengzhang novelmrnamirnaregulatorysubnetworkassociatedwithprognosisofmetastaticclearcellrenalcellcarcinoma |