MiR-494-3p promotes PI3K/AKT pathway hyperactivation and human hepatocellular carcinoma progression by targeting PTEN

Lin, Hui Yi; Huang, Zhiping; Liu, Jiao; Qiu, Yun; Tao, Yuan‐Ping; Wang, Meng-Chao; Yao, Hui; Hou, Kezhu; Gu, Fangming; Xu, Xuanfu

doi:10.1038/s41598-018-28519-2

Cited by 61 publications

(57 citation statements)

References 46 publications

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“…PRL-3 can enhance the phosphorylation level of PTEN, thus reducing its level. PTEN was identified as a negative switch of the AKT pathway, and its down-regulation can activate the AKT pathway, thus contributing to aggressive progression of HCC [ 39 ]. The targeted relationship between PRL-3 and PTEN was also reported by Xiong et al in gastric cancer [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Up-Regulation of Phosphatase in Regenerating Liver-3 (PRL-3) Contributes to Malignant Progression of Hepatocellular Carcinoma by Activating Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN)/Phosphoinositide 3-Kinase (PI3K)/AKT Signaling Pathway

Wang

et al. 2018

Med Sci Monit

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BackgroundThe purpose of the study was to investigate the functional roles of phosphatase in regenerating liver-3 (PRL-3) in hepatocellular carcinoma (HCC), as well as the related molecular mechanisms.Material/MethodsHCC tissues and adjacent normal tissues were collected from 124 HCC patients. The mRNA and protein levels of PRL-3 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays, respectively. The relationship between PRL-3 expression and clinical characteristics of HCC patients was evaluated by chi-square test. MTT and Transwell assays were performed to estimate cell proliferation and motility, respectively.ResultsThe expression of PRL-3 was significantly increased in HCC tissues and cells at both protein and mRNA levels (P<0.01 for all). Furthermore, the up-regulation of PRL-3 was positively correlated with hepatic vascular invasion (P=0.019), lymph node metastasis (P=0.012), and TNM stage (P=0.001). The knockdown of PRL-3 suppressed HCC cell proliferation, migration, and invasion, and PR3K/AKT pathway activity was also obviously inhibited in HCC cells with PRL-3 deficiency. The levels of PTEN were negatively associated with PRL-3 expression. PRL-3 might inhibit the protein level of PTEN through enhancing its phosphorylation level. The transfection of si-PTEN can reverse the anti-tumor action caused by PRL-3 knockdown in HCC cells.ConclusionsUp-regulation of PRL-3 may activate the PI3K/AKT signaling pathway and enhance malignant progression of HCC through targeting PTEN.

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Section: Discussionmentioning

confidence: 99%

Up-Regulation of Phosphatase in Regenerating Liver-3 (PRL-3) Contributes to Malignant Progression of Hepatocellular Carcinoma by Activating Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN)/Phosphoinositide 3-Kinase (PI3K)/AKT Signaling Pathway

Wang

et al. 2018

Med Sci Monit

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“…Lipofectamine 2000 (Invitrogen, Eugene, OR, USA) was used for transfection according to the manufacturer's protocol. PI3K activity was assayed as previously described [6]. PI3K inhibitor LY294002 was obtained from Abcam.…”

Section: Lca Cell Lines Cell Culture and Cell Transfectionmentioning

confidence: 99%

“…The colony formation assays were performed as previous [6]. Each group of treated cells (1 × 10 3 per well) was seeded into 10 cm culture dish, and cultured for 2 weeks.…”

Section: Colony Formation Assaymentioning

confidence: 99%

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miRNA-425-5p enhances lung cancer growth via the PTEN/PI3K/AKT signaling axis

et al. 2020

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Background: miRNAs regulate a multitude of cellular processes and their aberrant regulation is linked to human cancer. However, the role of miR-425-5p in lung cancer (LCa) is still largely unclear. Here, we explored the role of miR-425-5p during LCa tumorigenesis. Methods: Cell proliferation was evaluated by cell counting Kit-8 and colony formation assay. Western blot and realtime PCR were accordingly used to detect the relevant proteins, miRNA and gene expression. Luciferase reporter assays were used to illustrate the interaction between miR-425-5p and PTEN. Results: We demonstrate that miR-425-5p is overexpressed in LCa tissue and enhances the proliferative and colony formation capacity of the LCa cell lines A549 and NCI-H1299. Through predictive binding assays, PTEN was identified as a direct gene target and its exogenous expression inhibited the pro-cancer effects of miR-425-5p. Through its ability to down-regulate PTEN, miR-425-5p activated the PI3K/AKT axis. Conclusion: We conclude that miR-425-5p promotes LCa tumorigenesis through PTEN/PI3K/AKT signaling.

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“…By inhibiting PTEN hypermethylation, miR‐29b up‐regulates PTEN expression, resulting in the suppression of hepatic fibrosis 11 . On the contrary, miR‐494‐3p up‐regulates the PI3K/Akt pathway via targetting PTEN, causing the hepatocellular carcinoma aggravation 14 . Our previous study has shown that up‐regulated miR‐23a‐5p levels correlating with hepatocellular carcinoma 15 .…”

Section: Introductionmentioning

confidence: 97%

Identification lncRNA LOC102551149/miR‐23a‐5p pathway in hepatic fibrosis

Zhao

et al. 2020

Eur J Clin Investigation

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Background: Hepatic fibrosis is a worldwide incurable disease; due to the complex and unclear mechanism, there lack the effective therapeutic targets. However, the mechanism of miR-23a-5p underling this pathological process is largely not clear.The purpose of this study was to investigate the role of miR-23a-5p in hepatic fibrosis and HSC activation. Methods: The content of miR-23a-5p in hepatic fibrosis induced by Nnitrosodimethylamine (NDMA) and HSC activation induced by platelet-derived growth factor (PDGF) was detected by qRT-PCR. H&E staining, Masson staining and Shear wave electrography (SWE) were used to detect the degree of hepatic fibrosis. Immunohistochemistry staining, qRT-PCR and Western blot detect the related markers of liver fibrosis or HSC activation, as well as the related pathway genes and proteins. Dual-luciferase reporter system verifies the interaction between miR-23a-5p with PTEN or miR-23a-5p with lncRNA LOC102551149 in HSC-T6. siRNA and miRNA mimic transfer to HSC-T6 to detect the function of lncRNA LOC102551149 and miR-23a-5p on HSC activation. Results: After hepatic fibrosis and HSC activation happened, the expression of miR-23a-5p was up-regulated, whereas anti-miR-23a-5p can alleviate hepatic fibrosis and HSC activation. Further research shows miR-23a-5p can target PTEN and degrade it, causing activation of PI3K/Akt/mTOR/Snail pathway. lncRNA LOC102551149 can be used as a competition endogenous RNA (ceRNA) targeting miR-23a-5p through base pairing, and siRNA LOC102551149 or exogenous miR-23a-5p can induce HSC activation through PI3K/Akt/mTOR/Snail pathway. Conclusion: We demonstrate mechanism pathway of miR-23a-5p on hepatic fibrosis and HSC activation, which may develop a therapeutic target for hepatic fibrosis. K E Y W O R D S hepatic fibrosis, HSC activation, lncRNA LOC102551149, miR-23a-5p, PI3K/Akt, PTEN 2 of 14 | DONG et al.

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MiR-494-3p promotes PI3K/AKT pathway hyperactivation and human hepatocellular carcinoma progression by targeting PTEN

Cited by 61 publications

References 46 publications

Up-Regulation of Phosphatase in Regenerating Liver-3 (PRL-3) Contributes to Malignant Progression of Hepatocellular Carcinoma by Activating Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN)/Phosphoinositide 3-Kinase (PI3K)/AKT Signaling Pathway

Up-Regulation of Phosphatase in Regenerating Liver-3 (PRL-3) Contributes to Malignant Progression of Hepatocellular Carcinoma by Activating Phosphatase and Tensin Homolog Deleted on Chromosome Ten (PTEN)/Phosphoinositide 3-Kinase (PI3K)/AKT Signaling Pathway

miRNA-425-5p enhances lung cancer growth via the PTEN/PI3K/AKT signaling axis

Identification lncRNA LOC102551149/miR‐23a‐5p pathway in hepatic fibrosis

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