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LncRNA HOTAIR Promotes Cancer Stem-Like Cells Properties by Sponging miR-34a to Activate the JAK2/STAT3 Pathway in Pancreatic Ductal Adenocarcinoma

Authors Deng S, Wang J, Zhang L, Li J, Jin Y

Received 16 October 2020

Accepted for publication 16 February 2021

Published 12 March 2021 Volume 2021:14 Pages 1883—1893

DOI https://doi.org/10.2147/OTT.S286666

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Geoffrey Pietersz


Shikang Deng,1,2 Junfeng Wang,2 Li Zhang,2 Jiao Li,2 Yan Jin2

1Medical School, Kunming University of Science and Technology, Kunming, Yunnan, 650500, People’s Republic of China; 2Department of Hepatobiliary and Pancreatic Surgery, The First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, 650032, People’s Republic of China

Correspondence: Yan Jin
Department of Hepatobiliary and Pancreatic Surgery, The First People’s Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Xishan, Kunming, Yunnan, 650032, People’s Republic of China
Email [email protected]

Introduction: Pancreatic Ductal Adenocarcinoma (PDAC) stem cells (CSCs) play a vital role in the occurrence, development and recurrence of PDAC. Previous studies have shown that long non-coding RNAs (lncRNA) are closely associated with occurrence and development of malignant tumors. Among them, a LncRNA called homeobox transcription antisense RNA (HOTAIR) plays a key role in cancer progression in a variety of malignant tumors, including PDAC. Numerous studies have associated HOTAIR with poor prognosis of malignant tumor treatment, owing to its role in regulating downstream microRNAs (miRNAs). However, its underlying mechanism of action on CSCs-like properties of PDAC remain unclear.
Methods: We enriched CSCs of PDAC with a serum-free medium (SFM), and analyzed the expression levels of HOTAIR and miR-34a after enrichment. In addition, we evaluated the regulatory effects of HOTAIR and miR-34a on CSCs-like properties, invasion and migration of PDAC. Finally, we elucidated the role of HOTAIR in pancreatic tumor xenotransplantation.
Results: HOTAIR was upregulated in CSCs following PDAC enrichment of PDAC. Conversely, miR-34a was downregulated and appeared to be a direct target of HOTAIR. Moreover, knocking down HOTAIR or overexpressing miR-34a significantly inhibited CSCs-like properties, invasion and migration of PDAC cells. Furthermore, HOTAIR activated the JAK2/STAT3 pathway through miR-34a, thereby promoting CSCs-like properties, invasion and migration of PDAC cells. In vivo experiments indicated that knocking down HOTAIR could inhibit the tumorigenicity of CFPAC-1 cells.
Conclusion: This is the first report of HOTAIR-mediated activation of the JAK2/STAT3 pathway via miR-34a inhibition. This activation promotes CSCs-like properties, invasion and migration of PDAC.

Keywords: pancreatic ductal adenocarcinoma, lncRNA HOTAIR, miR-34a, CSCs-like properties, JAK2/STAT3 pathway

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