Long non-coding RNA TUG1 mediates 5-fluorouracil resistance by acting as a ceRNA of miR-197-3p in colorectal cancer
One major reason for the failure of advanced colorectal cancer (CRC) treatment is the occurrence of chemoresistance to fluoropyrimidine (Fu)-based chemotherapy. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play a critical role in cancerous processes as either oncogenes or tumo...
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| Veröffentlicht in: | Journal of Cancer Jg. 10; H. 19; S. 4603 - 4613 |
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| Abstract | One major reason for the failure of advanced colorectal cancer (CRC) treatment is the occurrence of chemoresistance to fluoropyrimidine (Fu)-based chemotherapy. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play a critical role in cancerous processes as either oncogenes or tumor suppressor genes. Here, we observed lncRNA TUG1 was associated to the 5-Fu resistance in colorectal cancer. Firstly, quantitative analysis indicated that TUG1 was significantly increased in recurrence CRC patient samples. Kaplan-Meier survival analysis indicated that high TUG1 expression in CRC tissues was significantly associated with a higher rate of disease progression. TUG1 knockdown re-sensitized the 5-Fu resistance in colorectal cancer cells, which were 5-Fu-resistant colorectal cell line. Furthermore, bioinformatics analysis showed that miR-197-3p could directly bind to TUG1 suggesting TUG1 might work as a ceRNA to sponge miR-197-3p. Extensively, our study also showed that TYMS was the direct target of miR-197-3p in CRC cells. Taken together, our study suggests that TUG1 mediates 5-Fu resistance in CRC via miR-197-3p/TYMS axis. |
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| AbstractList | One major reason for the failure of advanced colorectal cancer (CRC) treatment is the occurrence of chemoresistance to fluoropyrimidine (Fu)-based chemotherapy. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play a critical role in cancerous processes as either oncogenes or tumor suppressor genes. Here, we observed lncRNA TUG1 was associated to the 5-Fu resistance in colorectal cancer. Firstly, quantitative analysis indicated that TUG1 was significantly increased in recurrence CRC patient samples. Kaplan-Meier survival analysis indicated that high TUG1 expression in CRC tissues was significantly associated with a higher rate of disease progression. TUG1 knockdown re-sensitized the 5-Fu resistance in colorectal cancer cells, which were 5-Fu-resistant colorectal cell line. Furthermore, bioinformatics analysis showed that miR-197-3p could directly bind to TUG1 suggesting TUG1 might work as a ceRNA to sponge miR-197-3p. Extensively, our study also showed that TYMS was the direct target of miR-197-3p in CRC cells. Taken together, our study suggests that TUG1 mediates 5-Fu resistance in CRC via miR-197-3p/TYMS axis.One major reason for the failure of advanced colorectal cancer (CRC) treatment is the occurrence of chemoresistance to fluoropyrimidine (Fu)-based chemotherapy. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play a critical role in cancerous processes as either oncogenes or tumor suppressor genes. Here, we observed lncRNA TUG1 was associated to the 5-Fu resistance in colorectal cancer. Firstly, quantitative analysis indicated that TUG1 was significantly increased in recurrence CRC patient samples. Kaplan-Meier survival analysis indicated that high TUG1 expression in CRC tissues was significantly associated with a higher rate of disease progression. TUG1 knockdown re-sensitized the 5-Fu resistance in colorectal cancer cells, which were 5-Fu-resistant colorectal cell line. Furthermore, bioinformatics analysis showed that miR-197-3p could directly bind to TUG1 suggesting TUG1 might work as a ceRNA to sponge miR-197-3p. Extensively, our study also showed that TYMS was the direct target of miR-197-3p in CRC cells. Taken together, our study suggests that TUG1 mediates 5-Fu resistance in CRC via miR-197-3p/TYMS axis. One major reason for the failure of advanced colorectal cancer (CRC) treatment is the occurrence of chemoresistance to fluoropyrimidine (Fu)-based chemotherapy. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) play a critical role in cancerous processes as either oncogenes or tumor suppressor genes. Here, we observed lncRNA TUG1 was associated to the 5-Fu resistance in colorectal cancer. Firstly, quantitative analysis indicated that TUG1 was significantly increased in recurrence CRC patient samples. Kaplan-Meier survival analysis indicated that high TUG1 expression in CRC tissues was significantly associated with a higher rate of disease progression. TUG1 knockdown re-sensitized the 5-Fu resistance in colorectal cancer cells, which were 5-Fu-resistant colorectal cell line. Furthermore, bioinformatics analysis showed that miR-197-3p could directly bind to TUG1 suggesting TUG1 might work as a ceRNA to sponge miR-197-3p. Extensively, our study also showed that TYMS was the direct target of miR-197-3p in CRC cells. Taken together, our study suggests that TUG1 mediates 5-Fu resistance in CRC via miR-197-3p/TYMS axis. |
| Author | Huang, Rui Chen, Yinggang Zhang, Qian Wang, Meng Wang, Xishan Wu, Hongyu Hu, Hanqing Huang, Quanlong Qiao, Tianyu Chen, Qingmin Ma, Tianyi Wang, Yuliuming Wang, Guiyu Han, Dong |
| AuthorAffiliation | 1 Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China 4 Department of Colorectal Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100000, China 2 Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150081, China 3 Department of General Surgery, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang 157011, China |
| AuthorAffiliation_xml | – name: 1 Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin 150081, China – name: 4 Department of Colorectal Surgery, Cancer Institute and Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100000, China – name: 2 Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin 150081, China – name: 3 Department of General Surgery, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang 157011, China |
| Author_xml | – sequence: 1 givenname: Meng surname: Wang fullname: Wang, Meng – sequence: 2 givenname: Hanqing surname: Hu fullname: Hu, Hanqing – sequence: 3 givenname: Yuliuming surname: Wang fullname: Wang, Yuliuming – sequence: 4 givenname: Quanlong surname: Huang fullname: Huang, Quanlong – sequence: 5 givenname: Rui surname: Huang fullname: Huang, Rui – sequence: 6 givenname: Yinggang surname: Chen fullname: Chen, Yinggang – sequence: 7 givenname: Tianyi surname: Ma fullname: Ma, Tianyi – sequence: 8 givenname: Tianyu surname: Qiao fullname: Qiao, Tianyu – sequence: 9 givenname: Qian surname: Zhang fullname: Zhang, Qian – sequence: 10 givenname: Hongyu surname: Wu fullname: Wu, Hongyu – sequence: 11 givenname: Qingmin surname: Chen fullname: Chen, Qingmin – sequence: 12 givenname: Dong surname: Han fullname: Han, Dong – sequence: 13 givenname: Guiyu surname: Wang fullname: Wang, Guiyu – sequence: 14 givenname: Xishan surname: Wang fullname: Wang, Xishan |
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| SubjectTerms | Cancer therapies Chemotherapy Colorectal cancer Flow cytometry Gene expression Medical research Reagents Research Paper Surgery |
| Title | Long non-coding RNA TUG1 mediates 5-fluorouracil resistance by acting as a ceRNA of miR-197-3p in colorectal cancer |
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