Affordable Access

deepdyve-link
Publisher Website

MiR-499a-5p promotes 5-FU resistance and the cell proliferation and migration through activating PI3K/Akt signaling by targeting PTEN in pancreatic cancer.

Authors
  • Ouyang, Liu1
  • Liu, Ren-Dong2
  • Lei, De-Qiao3
  • Shang, Qing-Chao4
  • Li, Hui-Fen5
  • Hu, Xian-Gui1
  • Zheng, Hao6, 7
  • Jin, Gang1
  • 1 Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. , (China)
  • 2 Department of Hepatobiliary Surgery, General Hospital of Southern Theatre Command, Guangzhou, China. , (China)
  • 3 Department of General Surgery, General Hospital of Southern Theatre Command, Guangzhou, China. , (China)
  • 4 Department of Radiation Oncology, General Hospital of Southern Theatre Command, Guangzhou, China. , (China)
  • 5 Department of Hepatic Surgery & Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China. , (China)
  • 6 Department of Reproductive Heredity Center, Changhai Hospital, Second Military Medical University, Shanghai, China. , (China)
  • 7 Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China. , (China)
Type
Published Article
Journal
Annals of Translational Medicine
Publisher
AME Publishing Company
Publication Date
Dec 01, 2021
Volume
9
Issue
24
Pages
1798–1798
Identifiers
DOI: 10.21037/atm-21-6556
PMID: 35071492
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Pancreatic cancer (PC) can be considered a representative cancer type of the human body. As demonstrated by some studies, microRNA (miR)-499 is dysregulated in various cancer types including PC, for which chemotherapy involving 5-fluorouracil (5-FU) has long been considered the first-line therapy. However, there are complex and comprehensive mechanisms related to 5-FU, which have not been fully elucidated. This study thus aimed to examine the molecular mechanisms of 5-FU resistance through miR-499a-5p in PC. The expression of miR-499a-5p in PC was measured using quantitative polymerase chain reaction (PCR). MiR-499a-5p was examined in-vivo for its effects on the malignant phenotypes of PC cells. The results of the present study demonstrated miR-499a-5p to be upregulated in PC and 5-FU resistant PC tissues. According to in vitro assays in PC cells (PANC1/FR), miR-499a-5p was found to affect adenosine triphosphate (ATP) binding cassette subfamily B member 1 (P-gp), ATP binding cassette subfamily C member 1 (MRP1), and ATP binding cassette subfamily G member 2 (BCRP), thereby facilitating 5-FU resistance in PC cells. Functions assays indicated that suppressed miR-499a-5p expression inhibited the proliferation and migration of cells but facilitated apoptosis in the PC cell line; by contrast, miR-499a-5p overexpression triggered the inverse phenotypic changes of cells. Concerning the mechanisms involved, miR-499a-5p increased PI3K/Akt signaling by targeting phosphatase and tensin homolog (PTEN). Taken together, these findings demonstrate that miR-499a-5p can be potentially applied to PC therapy. 2021 Annals of Translational Medicine. All rights reserved.

Report this publication

Statistics

Seen <100 times