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Circular RNA circ-MTHFD1L induces HR repair to promote gemcitabine resistance via the miR-615-3p/RPN6 axis in pancreatic ductal adenocarcinoma
by
Chen, Zhi-Wen
, Hu, Jian-Fei
, Wang, Zu-Wei
, Tian, Yi-Feng
, Liao, Cheng-Yu
, Kang, Feng-Ping
, Lin, Cai-Feng
, Huang, Yi
, Chen, Shi
, Huang, Long
in
Adenocarcinoma
/ Analysis
/ Antimitotic agents
/ Antineoplastic agents
/ Apoptosis
/ Biomarkers
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer
/ Cancer Research
/ Cancer therapies
/ Carcinoma, Pancreatic Ductal - drug therapy
/ Carcinoma, Pancreatic Ductal - genetics
/ Carcinoma, Pancreatic Ductal - metabolism
/ Care and treatment
/ Cell cycle
/ Cell Line, Tumor
/ Cell Proliferation
/ Chemotherapy
/ Circ-MTHFD1L
/ Deoxycytidine - analogs & derivatives
/ Development and progression
/ DNA polymerase
/ Gemcitabine
/ Gemcitabine resistance
/ Gene expression
/ Genes
/ Genomes
/ Humans
/ Immunology
/ In Situ Hybridization, Fluorescence
/ Laws, regulations and rules
/ Long non-coding and circular RNAs in the landscape of cancer progression and metastasis
/ Medical prognosis
/ Methylenetetrahydrofolate Dehydrogenase (NADP) - genetics
/ MicroRNA
/ MicroRNAs - genetics
/ MicroRNAs - metabolism
/ Minor Histocompatibility Antigens - genetics
/ miR-615-3p
/ Mutation
/ Oncology
/ Pancreatic cancer
/ Pancreatic Neoplasms
/ Pancreatic Neoplasms - drug therapy
/ Pancreatic Neoplasms - genetics
/ Pancreatic Neoplasms - metabolism
/ RNA, Circular - genetics
/ RPN6
/ Tumors
2022
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Circular RNA circ-MTHFD1L induces HR repair to promote gemcitabine resistance via the miR-615-3p/RPN6 axis in pancreatic ductal adenocarcinoma
by
Chen, Zhi-Wen
, Hu, Jian-Fei
, Wang, Zu-Wei
, Tian, Yi-Feng
, Liao, Cheng-Yu
, Kang, Feng-Ping
, Lin, Cai-Feng
, Huang, Yi
, Chen, Shi
, Huang, Long
in
Adenocarcinoma
/ Analysis
/ Antimitotic agents
/ Antineoplastic agents
/ Apoptosis
/ Biomarkers
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer
/ Cancer Research
/ Cancer therapies
/ Carcinoma, Pancreatic Ductal - drug therapy
/ Carcinoma, Pancreatic Ductal - genetics
/ Carcinoma, Pancreatic Ductal - metabolism
/ Care and treatment
/ Cell cycle
/ Cell Line, Tumor
/ Cell Proliferation
/ Chemotherapy
/ Circ-MTHFD1L
/ Deoxycytidine - analogs & derivatives
/ Development and progression
/ DNA polymerase
/ Gemcitabine
/ Gemcitabine resistance
/ Gene expression
/ Genes
/ Genomes
/ Humans
/ Immunology
/ In Situ Hybridization, Fluorescence
/ Laws, regulations and rules
/ Long non-coding and circular RNAs in the landscape of cancer progression and metastasis
/ Medical prognosis
/ Methylenetetrahydrofolate Dehydrogenase (NADP) - genetics
/ MicroRNA
/ MicroRNAs - genetics
/ MicroRNAs - metabolism
/ Minor Histocompatibility Antigens - genetics
/ miR-615-3p
/ Mutation
/ Oncology
/ Pancreatic cancer
/ Pancreatic Neoplasms
/ Pancreatic Neoplasms - drug therapy
/ Pancreatic Neoplasms - genetics
/ Pancreatic Neoplasms - metabolism
/ RNA, Circular - genetics
/ RPN6
/ Tumors
2022
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Circular RNA circ-MTHFD1L induces HR repair to promote gemcitabine resistance via the miR-615-3p/RPN6 axis in pancreatic ductal adenocarcinoma
by
Chen, Zhi-Wen
, Hu, Jian-Fei
, Wang, Zu-Wei
, Tian, Yi-Feng
, Liao, Cheng-Yu
, Kang, Feng-Ping
, Lin, Cai-Feng
, Huang, Yi
, Chen, Shi
, Huang, Long
in
Adenocarcinoma
/ Analysis
/ Antimitotic agents
/ Antineoplastic agents
/ Apoptosis
/ Biomarkers
/ Biomedical and Life Sciences
/ Biomedicine
/ Cancer
/ Cancer Research
/ Cancer therapies
/ Carcinoma, Pancreatic Ductal - drug therapy
/ Carcinoma, Pancreatic Ductal - genetics
/ Carcinoma, Pancreatic Ductal - metabolism
/ Care and treatment
/ Cell cycle
/ Cell Line, Tumor
/ Cell Proliferation
/ Chemotherapy
/ Circ-MTHFD1L
/ Deoxycytidine - analogs & derivatives
/ Development and progression
/ DNA polymerase
/ Gemcitabine
/ Gemcitabine resistance
/ Gene expression
/ Genes
/ Genomes
/ Humans
/ Immunology
/ In Situ Hybridization, Fluorescence
/ Laws, regulations and rules
/ Long non-coding and circular RNAs in the landscape of cancer progression and metastasis
/ Medical prognosis
/ Methylenetetrahydrofolate Dehydrogenase (NADP) - genetics
/ MicroRNA
/ MicroRNAs - genetics
/ MicroRNAs - metabolism
/ Minor Histocompatibility Antigens - genetics
/ miR-615-3p
/ Mutation
/ Oncology
/ Pancreatic cancer
/ Pancreatic Neoplasms
/ Pancreatic Neoplasms - drug therapy
/ Pancreatic Neoplasms - genetics
/ Pancreatic Neoplasms - metabolism
/ RNA, Circular - genetics
/ RPN6
/ Tumors
2022
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Circular RNA circ-MTHFD1L induces HR repair to promote gemcitabine resistance via the miR-615-3p/RPN6 axis in pancreatic ductal adenocarcinoma
Journal Article
Circular RNA circ-MTHFD1L induces HR repair to promote gemcitabine resistance via the miR-615-3p/RPN6 axis in pancreatic ductal adenocarcinoma
2022
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Overview
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.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Analysis
/ Biomedical and Life Sciences
/ Cancer
/ Carcinoma, Pancreatic Ductal - drug therapy
/ Carcinoma, Pancreatic Ductal - genetics
/ Carcinoma, Pancreatic Ductal - metabolism
/ Deoxycytidine - analogs & derivatives
/ Genes
/ Genomes
/ Humans
/ In Situ Hybridization, Fluorescence
/ Long non-coding and circular RNAs in the landscape of cancer progression and metastasis
/ Methylenetetrahydrofolate Dehydrogenase (NADP) - genetics
/ MicroRNA
/ Minor Histocompatibility Antigens - genetics
/ Mutation
/ Oncology
/ Pancreatic Neoplasms - drug therapy
/ Pancreatic Neoplasms - genetics
/ Pancreatic Neoplasms - metabolism
/ RPN6
/ Tumors
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