Abstract | BACKGROUND: 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.
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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 |
Journal | Journal of experimental & clinical cancer research : CR
(J Exp Clin Cancer Res)
Vol. 41
Issue 1
Pg. 153
(Apr 23 2022)
ISSN: 1756-9966 [Electronic] England |
PMID | 35459186
(Publication Type: Journal Article)
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Copyright | © 2022. The Author(s). |
Chemical References |
- MIRN615 microRNA, human
- MicroRNAs
- Minor Histocompatibility Antigens
- RNA, Circular
- Deoxycytidine
- MTHFD1 protein, human
- Methylenetetrahydrofolate Dehydrogenase (NADP)
- Gemcitabine
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Topics |
- Carcinoma, Pancreatic Ductal
(drug therapy, genetics, metabolism)
- Cell Line, Tumor
- Cell Proliferation
- Deoxycytidine
(analogs & derivatives)
- Humans
- In Situ Hybridization, Fluorescence
- Methylenetetrahydrofolate Dehydrogenase (NADP)
(genetics)
- MicroRNAs
(genetics, metabolism)
- Minor Histocompatibility Antigens
(genetics)
- Pancreatic Neoplasms
(drug therapy, genetics, metabolism)
- RNA, Circular
(genetics)
- Gemcitabine
- Pancreatic Neoplasms
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