Biomaterial Database

MicroRNA-101-3p reverses gemcitabine resistance by inhibition of ribonucleotide reductase M1 in pancreatic cancer. 2016

Pei Fan, and Li Liu, and Yefeng Yin, and Zhefu Zhao, and Yiyao Zhang, and Prince S Amponsah, and Xi Xiao, and Nathalie Bauer, and Alia Abukiwan, and Clifford C Nwaeburu, and Jury Gladkich, and Chao Gao, and Peter Schemmer, and Wolfgang Gross, and Ingrid Herr

Molecular OncoSurgery, University of Heidelberg, Heidelberg, Germany; Section Surgical Research, University of Heidelberg, Heidelberg, Germany; Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany.

Pancreatic ductal adenocarcinoma (PDA) is among the most lethal malignancies and resistance to chemotherapy prevents the therapeutic outcome. MicroRNAs provide a novel therapeutic strategy. Here, the established and primary human PDA cell lines PANC-1, AsPC-1, MIA-PaCa2, AsanPaCa, BxPC-3 and three gemcitabine-resistant subclones were examined. A gene expression profiling revealed that the ribonucleotide reductase M1 (RRM1) was upregulated in gemcitabine-resistant cells, which was confirmed by qRT-PCR, Western blot analysis and immunostaining. Inhibition of RRM1 by lipotransfection of siRNA reduced its expression and reversed gemcitabine resistance. The expression of RRM1 correlated to gemcitabine resistance in vitro and was higher in malignant patient pancreas tissue compared to non-malignant pancreas tissue. By microRNA expression profiling, we identified microRNA-101-3p as top-downregulated candidate. Lipotransfection of microRNA-101-3p mimics inhibited the expression of RRM1, reduced the luciferase activity of its 3'UTR and sensitized for gemcitabine-induced cytotoxicity. These results underline the relevance of microRNA-101-3p-driven regulation of RRM1 in drug resistance and suggest the co-delivery of microRNA-101-3p and gemcitabine for more effective therapy outcome.

UI	MeSH Term	Description	Entries
D010190	Pancreatic Neoplasms	Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).	Cancer of Pancreas,Pancreatic Cancer,Cancer of the Pancreas,Neoplasms, Pancreatic,Pancreas Cancer,Pancreas Neoplasms,Pancreatic Acinar Carcinoma,Pancreatic Carcinoma,Acinar Carcinoma, Pancreatic,Acinar Carcinomas, Pancreatic,Cancer, Pancreas,Cancer, Pancreatic,Cancers, Pancreas,Cancers, Pancreatic,Carcinoma, Pancreatic,Carcinoma, Pancreatic Acinar,Carcinomas, Pancreatic,Carcinomas, Pancreatic Acinar,Neoplasm, Pancreas,Neoplasm, Pancreatic,Neoplasms, Pancreas,Pancreas Cancers,Pancreas Neoplasm,Pancreatic Acinar Carcinomas,Pancreatic Cancers,Pancreatic Carcinomas,Pancreatic Neoplasm
D003841	Deoxycytidine	A nucleoside component of DNA composed of CYTOSINE and DEOXYRIBOSE.	Cytosine Deoxyribonucleoside,Cytosine Deoxyriboside,Deoxyribonucleoside, Cytosine,Deoxyriboside, Cytosine
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000093542	Gemcitabine	A deoxycytidine antimetabolite used as an antineoplastic agent.	2',2'-Difluoro-2'-Deoxycytidine,2',2'-Difluorodeoxycytidine,2'-Deoxy-2',2''-Difluorocytidine-5'-O-Monophosphate,2'-Deoxy-2'-Difluorocytidine,Gemcitabine Hydrochloride,Gemcitabine, (D-threo-pentafuranosyl)-Isomer,Gemcitabine, (alpha-D-threo-pentofuranosyl)-Isomer,Gemcitabine, (beta-D-threo-pentafuranosyl)-Isomer,Gemicitabine,2',2'-DFDC,Gemzar,LY 188011,LY-188011,dFdCyd,188011, LY,2' Deoxy 2' Difluorocytidine,2' Deoxy 2',2'' Difluorocytidine 5' O Monophosphate,Hydrochloride, Gemcitabine
D000964	Antimetabolites, Antineoplastic	Antimetabolites that are useful in cancer chemotherapy.	Antineoplastic Antimetabolites
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D012262	Ribonucleoside Diphosphate Reductase	An enzyme of the oxidoreductase class that catalyzes the formation of 2'-deoxyribonucleotides from the corresponding ribonucleotides using NADPH as the ultimate electron donor. The deoxyribonucleoside diphosphates are used in DNA synthesis. (From Dorland, 27th ed) EC 1.17.4.1.	UDP Reductase,Diphosphate Reductase, Ribonucleoside,Reductase, Ribonucleoside Diphosphate,Reductase, UDP
D013997	Time Factors	Elements of limited time intervals, contributing to particular results or situations.	Time Series,Factor, Time,Time Factor
D014162	Transfection	The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.	Transfections