circFN1 Mediates Sorafenib Resistance of Hepatocellular Carcinoma Cells by Sponging miR-1205 and Regulating E2F1 Expression
In recent years, circular RNAs (circRNAs) have been shown to have critical regulatory roles in the resistance to anti-cancer drugs. However, the contributions of circRNAs to sorafenib resistance in hepatocellular carcinoma (HCC) remain largely unknown. The present study aims to explore the involveme...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-12-01
|
| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253120302699 |
| _version_ | 1818383891273089024 |
|---|---|
| author | Cheng Yang Zhitao Dong Han Hong Binghua Dai Feihong Song Li Geng Jiongjiong Lu Jiamei Yang Minhui Xu Chengjun Sui |
| author_facet | Cheng Yang Zhitao Dong Han Hong Binghua Dai Feihong Song Li Geng Jiongjiong Lu Jiamei Yang Minhui Xu Chengjun Sui |
| author_sort | Cheng Yang |
| collection | DOAJ |
| description | In recent years, circular RNAs (circRNAs) have been shown to have critical regulatory roles in the resistance to anti-cancer drugs. However, the contributions of circRNAs to sorafenib resistance in hepatocellular carcinoma (HCC) remain largely unknown. The present study aims to explore the involvement of circFN1 in sorafenib resistance and how circFN1 is associated with the miR-1205/E2F1 pathway, which have been demonstrated to mediate this resistance in HCC cells. We investigated the expression of circRNAs in five paired sorafenib-sensitive HepG2 cells and sorafenib-resistant (SR)-HepG2 cells by microarray analysis. The quantitative real-time PCR analysis was used to investigate the expression pattern of circFN1 in HCC patient tissues and cell lines. Then, the effects of circFN1 on sorafenib resistance, cell proliferation, and apoptosis were assessed in HCC in vitro and in vivo. In this study, circFN1 was observed to be upregulated in HCC patient tissues and cell lines. Overexpression of circFN1 in HCC was significantly correlated with aggressive characteristics and served as an independent risk factor for overall survival in patients with HCC. Our in vivo and in vitro data indicated that inhibition of circFN1 enhances the sorafenib sensitivity of HCC cells. Mechanistically, we found that circFN1 could promote the expression of E2F1 by sponging miR-1205. In summary, our study demonstrated that circFN1 contributes to sorafenib resistance by regulating the miR-1205/E2F1 signaling pathway. These results indicate that circFN1 may represent a potentially valuable target for overcoming sorafenib resistance for HCC. |
| first_indexed | 2024-12-14T03:13:34Z |
| format | Article |
| id | doaj.art-feae43f3229246ebb3fafb0ea2b323ca |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-14T03:13:34Z |
| publishDate | 2020-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-feae43f3229246ebb3fafb0ea2b323ca2022-12-21T23:19:12ZengElsevierMolecular Therapy: Nucleic Acids2162-25312020-12-0122421433circFN1 Mediates Sorafenib Resistance of Hepatocellular Carcinoma Cells by Sponging miR-1205 and Regulating E2F1 ExpressionCheng Yang0Zhitao Dong1Han Hong2Binghua Dai3Feihong Song4Li Geng5Jiongjiong Lu6Jiamei Yang7Minhui Xu8Chengjun Sui9Department of Special Treatment I and Liver Transplantation, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, ChinaDepartment of Special Treatment I and Liver Transplantation, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, ChinaDepartment of Hepato-Pancreato-Biliary Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215001, ChinaDepartment of Special Treatment I and Liver Transplantation, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, ChinaDepartment of Special Treatment I and Liver Transplantation, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, ChinaDepartment of Special Treatment I and Liver Transplantation, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, ChinaDepartment of Special Treatment I and Liver Transplantation, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, ChinaDepartment of Special Treatment I and Liver Transplantation, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, ChinaDepartment of Hepato-Pancreato-Biliary Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215001, China; Corresponding author: Minhui Xu, Department of Hepato-Pancreato-Biliary Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215001, China.Department of Special Treatment I and Liver Transplantation, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China; Corresponding author: Chengjun Sui, Department of Special Treatment I and Liver Transplantation, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China.In recent years, circular RNAs (circRNAs) have been shown to have critical regulatory roles in the resistance to anti-cancer drugs. However, the contributions of circRNAs to sorafenib resistance in hepatocellular carcinoma (HCC) remain largely unknown. The present study aims to explore the involvement of circFN1 in sorafenib resistance and how circFN1 is associated with the miR-1205/E2F1 pathway, which have been demonstrated to mediate this resistance in HCC cells. We investigated the expression of circRNAs in five paired sorafenib-sensitive HepG2 cells and sorafenib-resistant (SR)-HepG2 cells by microarray analysis. The quantitative real-time PCR analysis was used to investigate the expression pattern of circFN1 in HCC patient tissues and cell lines. Then, the effects of circFN1 on sorafenib resistance, cell proliferation, and apoptosis were assessed in HCC in vitro and in vivo. In this study, circFN1 was observed to be upregulated in HCC patient tissues and cell lines. Overexpression of circFN1 in HCC was significantly correlated with aggressive characteristics and served as an independent risk factor for overall survival in patients with HCC. Our in vivo and in vitro data indicated that inhibition of circFN1 enhances the sorafenib sensitivity of HCC cells. Mechanistically, we found that circFN1 could promote the expression of E2F1 by sponging miR-1205. In summary, our study demonstrated that circFN1 contributes to sorafenib resistance by regulating the miR-1205/E2F1 signaling pathway. These results indicate that circFN1 may represent a potentially valuable target for overcoming sorafenib resistance for HCC.http://www.sciencedirect.com/science/article/pii/S2162253120302699circRNAscircFN1microR-1205E2F1hepatocellular carcinomasorafenib |
| spellingShingle | Cheng Yang Zhitao Dong Han Hong Binghua Dai Feihong Song Li Geng Jiongjiong Lu Jiamei Yang Minhui Xu Chengjun Sui circFN1 Mediates Sorafenib Resistance of Hepatocellular Carcinoma Cells by Sponging miR-1205 and Regulating E2F1 Expression Molecular Therapy: Nucleic Acids circRNAs circFN1 microR-1205 E2F1 hepatocellular carcinoma sorafenib |
| title | circFN1 Mediates Sorafenib Resistance of Hepatocellular Carcinoma Cells by Sponging miR-1205 and Regulating E2F1 Expression |
| title_full | circFN1 Mediates Sorafenib Resistance of Hepatocellular Carcinoma Cells by Sponging miR-1205 and Regulating E2F1 Expression |
| title_fullStr | circFN1 Mediates Sorafenib Resistance of Hepatocellular Carcinoma Cells by Sponging miR-1205 and Regulating E2F1 Expression |
| title_full_unstemmed | circFN1 Mediates Sorafenib Resistance of Hepatocellular Carcinoma Cells by Sponging miR-1205 and Regulating E2F1 Expression |
| title_short | circFN1 Mediates Sorafenib Resistance of Hepatocellular Carcinoma Cells by Sponging miR-1205 and Regulating E2F1 Expression |
| title_sort | circfn1 mediates sorafenib resistance of hepatocellular carcinoma cells by sponging mir 1205 and regulating e2f1 expression |
| topic | circRNAs circFN1 microR-1205 E2F1 hepatocellular carcinoma sorafenib |
| url | http://www.sciencedirect.com/science/article/pii/S2162253120302699 |
| work_keys_str_mv | AT chengyang circfn1mediatessorafenibresistanceofhepatocellularcarcinomacellsbyspongingmir1205andregulatinge2f1expression AT zhitaodong circfn1mediatessorafenibresistanceofhepatocellularcarcinomacellsbyspongingmir1205andregulatinge2f1expression AT hanhong circfn1mediatessorafenibresistanceofhepatocellularcarcinomacellsbyspongingmir1205andregulatinge2f1expression AT binghuadai circfn1mediatessorafenibresistanceofhepatocellularcarcinomacellsbyspongingmir1205andregulatinge2f1expression AT feihongsong circfn1mediatessorafenibresistanceofhepatocellularcarcinomacellsbyspongingmir1205andregulatinge2f1expression AT ligeng circfn1mediatessorafenibresistanceofhepatocellularcarcinomacellsbyspongingmir1205andregulatinge2f1expression AT jiongjionglu circfn1mediatessorafenibresistanceofhepatocellularcarcinomacellsbyspongingmir1205andregulatinge2f1expression AT jiameiyang circfn1mediatessorafenibresistanceofhepatocellularcarcinomacellsbyspongingmir1205andregulatinge2f1expression AT minhuixu circfn1mediatessorafenibresistanceofhepatocellularcarcinomacellsbyspongingmir1205andregulatinge2f1expression AT chengjunsui circfn1mediatessorafenibresistanceofhepatocellularcarcinomacellsbyspongingmir1205andregulatinge2f1expression |