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Full Length Article | Open Access

Down-regulation of microRNA-23a promotes pancreatic ductal adenocarcinoma initiation and progression by up-regulation of FOXM1 expression

Lixin Lianga,1, Tian Caib,1, Xiaojia Lia,1, Jianhong Ana,1, Sen Yua, Yang Zhanga, Fengjie Guoa, Fang Weic, Jie Hec, Keping Xiea,c( ), Tingting Jianga( )
Center for Pancreatic Cancer Research, South China University of Technology School of Medicine, Guangzhou, Guangdong 510006, China
Department of Laboratory Medicine, The Sixth Affiliated Hospital and Nanhai People’s Hospital, South China University of Technology School of Medicine, Foshan, Guangdong 528200, China
The Second Affiliated Hospital and Guangzhou First People’s Hospital, South China University of Technology School of Medicine, Guangzhou, Guangdong 510006, China

Peer review under responsibility of Chongqing Medical University.

1 These authors contributed equally to this work and shared the co-first authorship.

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Abstract

Transcriptional factor Forkhead box M1 (FOXM1) plays an important role in pancreatic ductal adenocarcinoma (PDAC) development and progression. The molecular mechanisms underlying its dysregulation remain unclear. We identified and functionally validated the microRNAs (miRNAs) that critically regulate FOXM1 expression in PDAC. The expression levels of miRNA-23a (miR-23a-3p and -5p) were altered in PDAC cell lines and their effects on FOXM1 signaling and cell proliferation and migration and tumorigenesis were examined in vitro and in vivo using mouse PDAC models. Compared with non-tumor pancreatic tissues, PDAC tissues and cell lines exhibited significantly reduced levels of miR-23a expression. Reduced miR-23a expression and concomitant increase in FOXM1 expression were also observed in acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasia, the major premalignant lesions of PDAC. Transgenic expression of miR-23a reduced the expression of FOXM1 and suppressed cell proliferation and migration in PDAC cells, whereas the inhibitors of miR-23a did the opposite. Loss or reduced levels of miR-23a increased the levels of FOXM1 expression, while increased expression of FOXM1 down-regulated miR-23a expression, suggesting that miR-23a and FOXM1 were mutual negative regulators of their expression in PDAC cells. Therefore, the miR-23a/FOXM1 signaling axis is important in PDAC initiation and progression and could serve as an interventional or therapeutic target for patients with early or late stages of PDAC.

Keywords

FOXM1Gene expressionGene regulationMicroRNAPancreatic cancerTargeted therapy

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Genes & Diseases
Volume 11 Issue 5,
September 2024
Article number: 101203
DOI: 10.1016/j.gendis.2023.101203
Cite this article:
Liang L, Cai T, Li X, et al. Down-regulation of microRNA-23a promotes pancreatic ductal adenocarcinoma initiation and progression by up-regulation of FOXM1 expression. Genes & Diseases, 2024, 11(5): 101203. https://doi.org/10.1016/j.gendis.2023.101203

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Received: 05 August 2023
Revised: 19 October 2023
Accepted: 19 November 2023
Published: 22 December 2023
© 2023 The Authors.

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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