Downregulation of miR-374b-5p promotes chemotherapeutic resistance in pancreatic cancer by upregulating multiple anti-apoptotic proteins

Sun,Di; Wang,Xu; Sui,Guoqing; Chen,Si; Yu,Miao; Zhang,Ping

doi:10.3892/ijo.2018.4315

Downregulation of miR-374b-5p promotes chemotherapeutic resistance in pancreatic cancer by upregulating multiple anti-apoptotic proteins

Authors:
- Di Sun
- Xu Wang
- Guoqing Sui
- Si Chen
- Miao Yu
- Ping Zhang
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Affiliations: Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun, Jilin 130000, P.R. China, Department of Ultrasound, The China-Japan Union Hospital of Jilin University, Changchun, Jilin 130000, P.R. China, Center for Private Medical Service and Healthcare, The First Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Hepatobiliary and Pancreas Surgery, The First Hospital of Jilin University, Changchun, Jilin 130000, P.R. China
Published online on: March 14, 2018 https://doi.org/10.3892/ijo.2018.4315
Pages: 1491-1503
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Resistance to first-line chemotherapeutic drugs such as gemcitabine contributes to the poor prognosis of patients with pancreatic cancer. MicroRNAs (miRNA) regulate chemoresistance in pancreatic cancer. By analyzing the miRNA sequencing dataset of pancreatic cancer from The Cancer Genome Atlas, it was demonstrated that miR-374b-5p expression was dramatically reduced in pancreatic cancer tissues compared with adjacent normal tissues, as well as decreased in chemoresistant compared with chemosensitive pancreatic carcinoma tissues. The decreased expression of miR-374-5p was associated with poor overall and progression-free survival in patients with pancreatic cancer. Furthermore, increased expression of miR-374b-5p abrogated, while the silencing miR-374b-5p increased the chemoresistance of pancreatic cancer cells to gemcitabine in vitro. Importantly, the upregulation of miR-374b-5p ameliorated the chemoresistance of pancreatic cancer cells to gemcitabine in vivo. It was also demonstrated that miR-374b-5p targeted several anti-apoptotic proteins, including B-cell lymphoma 2, Baculoviral IAP Repeat Containing 3 and X-linked inhibitor of apoptosis in pancreatic cancer cells, which further attenuated chemoresistance in pancreatic cancer. Therefore, the results of the current study indicate that miR-374b-5p serves as a potential diagnostic marker. It also suggests that miR-374b-5p sensitizes cells to chemotherapy and may be used in combination with chemotherapeutic agents such as gemcitabine to treat patients with pancreatic cancer.

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