Bibliographic Details
| Title: |
Circular RNA circ-MTHFD1L induces HR repair to promote gemcitabine resistance via the miR-615-3p/RPN6 axis in pancreatic ductal adenocarcinoma |
| Authors: |
Zhi-Wen Chen, Jian-Fei Hu, Zu-Wei Wang, Cheng-Yu Liao, Feng-Ping Kang, Cai-Feng Lin, Yi Huang, Long Huang, Yi-Feng Tian, Shi Chen |
| Source: |
Journal of Experimental & Clinical Cancer Research, Vol 41, Iss 1, Pp 1-23 (2022) |
| Publisher Information: |
BMC, 2022. |
| Publication Year: |
2022 |
| Collection: |
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| Subject Terms: |
Circ-MTHFD1L, miR-615-3p, RPN6, Gemcitabine resistance, Pancreatic cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| More Details: |
Abstract Background Chemoresistance of pancreatic cancer is the main reason for the poor treatment effect of pancreatic cancer patients. Exploring chemotherapy resistance-related genes has been a difficult and hot topic of oncology. Numerous studies implicate the key roles of circular RNAs (circRNAs) in the development of pancreatic cancer. However, the regulation of circRNAs in the process of pancreatic ductal adenocarcinoma (PDAC) chemotherapy resistance is not yet fully clear. Methods Based on the cross-analysis of the Gene Expression Omnibus (GEO) database and the data of our center, we explored a new molecule, hsa_circ_0078297 (circ-MTHFD1L), related to chemotherapy resistance. QRT-PCR was used to detect the expression of circRNAs, miRNAs, and mRNAs in human PDAC tissues and their matched normal tissues. The interaction between circ-MTHFD1L and miR-615-3p/RPN6 signal axis was confirmed by a series of experiments such as Dual-luciferase reporter assay, fluorescence in situ hybridization (FISH) RNA immunoprecipitation (RIP) assays. Results Circ-MTHFD1L was significantly increased in PDAC tissues and cells. And in PDAC patients, the higher the expression level of circ-MTHFD1L, the worse the prognosis. Mechanism analysis showed that circ-MTHFD1L, as an endogenous miR-615-3p sponge, upregulates the expression of RPN6, thereby promoting DNA damage repair and exerting its effect on enhancing gemcitabine chemotherapy resistance. More importantly, we also found that Silencing circ-MTHFD1L combined with olaparib can increase the sensitivity of pancreatic cancer to gemcitabine. Conclusion Circ-MTHFD1L maintains PDAC gemcitabine resistance through the miR-615-3p/RPN6 signal axis. Circ-MTHFD1L may be a molecular marker for the effective treatment of PDAC. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1756-9966 |
| Relation: |
https://doaj.org/toc/1756-9966 |
| DOI: |
10.1186/s13046-022-02343-z |
| Access URL: |
https://doaj.org/article/7531f87a79cd424fb38f8d597e17e0f2 |
| Accession Number: |
edsdoj.7531f87a79cd424fb38f8d597e17e0f2 |
| Database: |
Directory of Open Access Journals |
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