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

Autor:	Shanyu Qin, Xiang-lian Zhang, Qiu-Yue Shi, Xi Wei, Hai-Xing Jiang, You-Yi Huang, Xin Qiu
Rok vydání:	2020
Předmět:	0301 basic medicine PI3K/Akt hepatoma malignant ascites Chemistry medicine.medical_treatment Cellular differentiation HIF-1α P70-S6 Kinase 1 Transfection miR-145 Th9 cells 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Cytokine Oncology 030220 oncology & carcinogenesis Ribosomal protein s6 medicine Cancer research Pharmacology (medical) Interleukin 9 Protein kinase B PI3K/AKT/mTOR pathway Original Research
Zdroj:	OncoTargets and therapy
ISSN:	1178-6930
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a5d7ea4fda7cc051d4201d0021ffaccd https://pubmed.ncbi.nlm.nih.gov/32440147 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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