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miR-145 Inhibits Th9 Cell Differentiation by Suppressing Activation of the PI3K/Akt/mTOR/p70S6K/HIF-1α Pathway in Malignant Ascites from Liver Cancer

Authors Huang YY, Jiang HX, Shi QY, Qiu X, Wei X, Zhang XL, Qin SY

Received 9 January 2020

Accepted for publication 10 April 2020

Published 5 May 2020 Volume 2020:13 Pages 3789—3800

DOI https://doi.org/10.2147/OTT.S245346

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Sanjeev Srivastava


You-Yi Huang, Hai-Xing Jiang, Qiu-Yue Shi, Xin Qiu, Xi Wei, Xiang-Lian Zhang, Shan-Yu Qin

Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, People’s Republic of China

Correspondence: Shan-Yu Qin
Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, People’s Republic of China
Tel +86 13977110511
Email qsy0511@163.com

Purpose: Our previous experiments confirmed that T helper type 9 (Th9) cells were involved in the occurrence and development of malignant ascites caused by liver cancer. The current study investigated the mechanism underlying microRNA (miR-145)-mediated inhibition of Th9 cells in an malignant ascites model with liver cancer.
Materials and Methods: CD4+ T cells were induced to differentiate Th9 cells after transfection with miR-145 mimics or negative control. A malignant ascites mouse model was transfected with miR-145agomir or negative control. Th9 cells were detected by flow cytometry. Enzyme-linked immunosorbent assay was applied to detect the interleukin 9 (IL-9) cytokine and hypoxia-inducible factor 1 alpha (HIF-1α). RT-PCR was used to detect the expression of miR-145 and phosphatidylinositol-3-kinase/Akt/mammalian target of rapamycin/p70 ribosomal protein S6 kinase/HIF-1α (PI3K/Akt/mTOR/p70S6K/HIF-1α) mRNA. Western blotting and immunofluorescence were performed to detect the expression of PI3K/Akt/mTOR/p70S6K/HIF-1α-related proteins.
Results: In vitro experiments showed that miR-145 inhibited Th9 cell polarization, HIF-1α expression, and PI3K/Akt/mTOR/p70S6K pathway activation. In the malignant ascites mouse model, miR-145 also demonstrated inhibitory effects on Th9 cell differentiation through the PI3K/Akt/mTOR/p70S6K/HIF-1α pathway.
Conclusion: miR-145 may inhibit Th9 cell differentiation through the PI3K/Akt/mTOR/p70S6K/HIF-1α pathway. These findings suggest a novel therapeutic target for malignant ascites from liver cancer.

Keywords: miR-145, Th9 cells, PI3K/Akt, HIF-1α, hepatoma malignant ascites

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