Cargando…
MiR-20a-5p regulates gemcitabine chemosensitivity by targeting RRM2 in pancreatic cancer cells and serves as a predictor for gemcitabine-based chemotherapy
Ribonucleotide reductase subunit M2 (RRM2) acts as an important gemcitabine resistance-related gene in pancreatic cancer (PC). Here, we aimed to investigate the potential microRNA that regulates gemcitabine chemosensitivity by targeting RRM2 and explores the clinical significance of candidate miRNA...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504660/ https://www.ncbi.nlm.nih.gov/pubmed/30777929 http://dx.doi.org/10.1042/BSR20181374 |
_version_ | 1783416605890314240 |
---|---|
author | Lu, Huimin Lu, Shan Yang, Dujiang Zhang, Ling Ye, Jun Li, Mao Hu, Weiming |
author_facet | Lu, Huimin Lu, Shan Yang, Dujiang Zhang, Ling Ye, Jun Li, Mao Hu, Weiming |
author_sort | Lu, Huimin |
collection | PubMed |
description | Ribonucleotide reductase subunit M2 (RRM2) acts as an important gemcitabine resistance-related gene in pancreatic cancer (PC). Here, we aimed to investigate the potential microRNA that regulates gemcitabine chemosensitivity by targeting RRM2 and explores the clinical significance of candidate miRNA in PC. MTT assay and Western blot analysis revealed that long-time gemcitabine treatment in PC cells induced drug resistance and RRM2 increase, and silence of RRM2 blocked gemcitabine resistance. Among the predicted eight RRM2-related microRNAs, the expression of miR-20a-5p showed the most significant discrepancy between gemcitabine-resistant cells and parental cells. Furthermore, the Dual-Luciferase reporter gene assay indicated that miR-20a-5p directly targeted RRM2 3′UTR, thus inhibited expression of RRM2 and overcame gemcitabine resistance of PC cells. Retrospective study suggested that plasma miR-20a-5p level was correlated with gemcitabine resistance in PC patient. ROC curve showed that miR-20a-5p abundant level might predict gemcitabine resistance with an AUC of 89% (P<0.0001). Additionally, the PFS of patients with high and low expression levels miR-20a-5p was 2.8 and 4.5 months (P<0.001), respectively. Taken together, our results suggests that miR-20a-5p regulated gemcitabine chemosensitivity by targeting RRM2 in PC cells and could serve as a predictor for predicting the efficacy of gemcitabine-based chemotherapy in first-line treatment of PC patients. |
format | Online Article Text |
id | pubmed-6504660 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65046602019-05-20 MiR-20a-5p regulates gemcitabine chemosensitivity by targeting RRM2 in pancreatic cancer cells and serves as a predictor for gemcitabine-based chemotherapy Lu, Huimin Lu, Shan Yang, Dujiang Zhang, Ling Ye, Jun Li, Mao Hu, Weiming Biosci Rep Research Articles Ribonucleotide reductase subunit M2 (RRM2) acts as an important gemcitabine resistance-related gene in pancreatic cancer (PC). Here, we aimed to investigate the potential microRNA that regulates gemcitabine chemosensitivity by targeting RRM2 and explores the clinical significance of candidate miRNA in PC. MTT assay and Western blot analysis revealed that long-time gemcitabine treatment in PC cells induced drug resistance and RRM2 increase, and silence of RRM2 blocked gemcitabine resistance. Among the predicted eight RRM2-related microRNAs, the expression of miR-20a-5p showed the most significant discrepancy between gemcitabine-resistant cells and parental cells. Furthermore, the Dual-Luciferase reporter gene assay indicated that miR-20a-5p directly targeted RRM2 3′UTR, thus inhibited expression of RRM2 and overcame gemcitabine resistance of PC cells. Retrospective study suggested that plasma miR-20a-5p level was correlated with gemcitabine resistance in PC patient. ROC curve showed that miR-20a-5p abundant level might predict gemcitabine resistance with an AUC of 89% (P<0.0001). Additionally, the PFS of patients with high and low expression levels miR-20a-5p was 2.8 and 4.5 months (P<0.001), respectively. Taken together, our results suggests that miR-20a-5p regulated gemcitabine chemosensitivity by targeting RRM2 in PC cells and could serve as a predictor for predicting the efficacy of gemcitabine-based chemotherapy in first-line treatment of PC patients. Portland Press Ltd. 2019-05-07 /pmc/articles/PMC6504660/ /pubmed/30777929 http://dx.doi.org/10.1042/BSR20181374 Text en © 2019 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Articles Lu, Huimin Lu, Shan Yang, Dujiang Zhang, Ling Ye, Jun Li, Mao Hu, Weiming MiR-20a-5p regulates gemcitabine chemosensitivity by targeting RRM2 in pancreatic cancer cells and serves as a predictor for gemcitabine-based chemotherapy |
title | MiR-20a-5p regulates gemcitabine chemosensitivity by targeting RRM2 in pancreatic cancer cells and serves as a predictor for gemcitabine-based chemotherapy |
title_full | MiR-20a-5p regulates gemcitabine chemosensitivity by targeting RRM2 in pancreatic cancer cells and serves as a predictor for gemcitabine-based chemotherapy |
title_fullStr | MiR-20a-5p regulates gemcitabine chemosensitivity by targeting RRM2 in pancreatic cancer cells and serves as a predictor for gemcitabine-based chemotherapy |
title_full_unstemmed | MiR-20a-5p regulates gemcitabine chemosensitivity by targeting RRM2 in pancreatic cancer cells and serves as a predictor for gemcitabine-based chemotherapy |
title_short | MiR-20a-5p regulates gemcitabine chemosensitivity by targeting RRM2 in pancreatic cancer cells and serves as a predictor for gemcitabine-based chemotherapy |
title_sort | mir-20a-5p regulates gemcitabine chemosensitivity by targeting rrm2 in pancreatic cancer cells and serves as a predictor for gemcitabine-based chemotherapy |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504660/ https://www.ncbi.nlm.nih.gov/pubmed/30777929 http://dx.doi.org/10.1042/BSR20181374 |
work_keys_str_mv | AT luhuimin mir20a5pregulatesgemcitabinechemosensitivitybytargetingrrm2inpancreaticcancercellsandservesasapredictorforgemcitabinebasedchemotherapy AT lushan mir20a5pregulatesgemcitabinechemosensitivitybytargetingrrm2inpancreaticcancercellsandservesasapredictorforgemcitabinebasedchemotherapy AT yangdujiang mir20a5pregulatesgemcitabinechemosensitivitybytargetingrrm2inpancreaticcancercellsandservesasapredictorforgemcitabinebasedchemotherapy AT zhangling mir20a5pregulatesgemcitabinechemosensitivitybytargetingrrm2inpancreaticcancercellsandservesasapredictorforgemcitabinebasedchemotherapy AT yejun mir20a5pregulatesgemcitabinechemosensitivitybytargetingrrm2inpancreaticcancercellsandservesasapredictorforgemcitabinebasedchemotherapy AT limao mir20a5pregulatesgemcitabinechemosensitivitybytargetingrrm2inpancreaticcancercellsandservesasapredictorforgemcitabinebasedchemotherapy AT huweiming mir20a5pregulatesgemcitabinechemosensitivitybytargetingrrm2inpancreaticcancercellsandservesasapredictorforgemcitabinebasedchemotherapy |