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. 2021 Oct 1;50(9):1260-1266.
doi: 10.1097/MPA.0000000000001920.

MicroRNA-34a Alleviates Gemcitabine Resistance in Pancreatic Cancer by Repression of Cancer Stem Cell Renewal

Yue Pan  1 , Kun Li  1 , Xufeng Tao  1 , Yongxin Zhao  2 , Qing Chen  1 , Ning Li  1 , Jianzhou Liu  1 , Vay Liang W Go  3 , Junchao Guo  4 , Ge Gao  2 , Gary Guishan Xiao
Affiliations

MicroRNA-34a Alleviates Gemcitabine Resistance in Pancreatic Cancer by Repression of Cancer Stem Cell Renewal

Yue Pan et al. Pancreas. .

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.

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Conflict of interest statement

The authors declare no conflict of interest.

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