MicroRNA-34a Alleviates Gemcitabine Resistance in Pancreatic Cancer by Repression of Cancer Stem Cell Renewal. Issue 9 (3rd October 2021)

• Record Type: Journal Article
• Authors: Pan, Yue; Li, Kun; Tao, Xufeng; Zhao, Yongxin; Chen, Qing; Li, Ning; Liu, Jianzhou; Go, Vay Liang W.; Guo, Junchao; Gao, Ge; Xiao, Gary Guishan
• Is Part Of: Pancreas. Volume 50:Issue 9(2021)
• Page Start: 1260
• Page End: 1266
• Publication Date: 2021-10-03
• Subjects: microRNA-34a -- gemcitabine resistance -- pancreatic cancer stem cell -- Notch 1 -- EMT; Pancreas -- Diseases -- Periodicals; Pancreas -- Periodicals; Neuroendocrine tumors -- Periodicals; 616.37005
• DOI: 10.1097/MPA.0000000000001920
• Languages: English
• ISSNs: 0885-3177

Abstract

Abstract : Objectives: This study aimed to enhance the sensitivity of pancreatic ductal adenocarcinoma cells by microRNA-34a (miR-34a)–mediated targeting of Notch 1. Methods: Cell viability was determined by using an MTT (3-(4, 5)-dimethylthiahiazo(−2)-3, 5-diphenytetrazoliumromide) assay. The expression levels of miR-34a and relevant mRNAs were determined using quantitative polymerase chain reaction. Protein levels were measured by Western blotting. Cellular stemness was assessed by cell invasiveness and sphere formation assays. A transplanted tumor model was established for in vivo experiments. Results: MicroRNA-34a enhanced gemcitabine sensitivity both in vivo and in vitro. MicroRNA-34a suppressed the stemness and proliferation of pancreatic cancer stem cells. MicroRNA-34a directly associated with Notch 1, which lies upstream of epithelial-mesenchymal transition signaling pathways. Conclusions: MicroRNA-34a sensitized pancreatic cancer cells to gemcitabine treatment by inhibiting Notch 1 signaling in pancreatic cancer stem cells, indicating that miR-34a has the potential to be developed as a novel therapeutic agent for the treatment of gemcitabine-resistant pancreatic ductal adenocarcinoma cells.