Long Noncoding RNA NEAT1 Promotes Cell Proliferation And Invasion And Suppresses Apoptosis In Hepatocellular Carcinoma By Regulating MiRNA-22-3p/akt2 In Vitro And In Vivo

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2019 Dec 6

PMID 31802908

Citations 13

Authors

Xichang Zhou

Xiang Wang

Yizhou Zhou

Long Cheng

Youwei Zhang

Yangmei Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Hepatocellular carcinoma (HCC) is one of the most aggressive cancers that is associated with cirrhosis and other chronic liver diseases. Although remarkable progress has been made in past decades, it is still necessary to continue exploring the pathology and development of HCC.

Objective: In this study, we elucidated the effect of long noncoding RNA (lncRNA) NEAT1 on HCC development and underlying mechanisms.

Methods: Clinicopathological features of HCC patients were collected and the correlations with NEAT1 expression were assessed. To determine cell activities, CCK-8, flow cytometry, invasion assays, and TUNEL assays were performed. Real-time PCR, Western blot, and luciferase reporter assays were performed to investigate the related mechanism of HCC.

Results: The results revealed that NEAT1 expression was associated with tumor size and differentiation where NEAT1 was upregulated in both HCC tissues and cell lines. Overexpression of NEAT1 promoted proliferation and invasion while inhibited apoptosis in HCC cells, which was opposite to the effect of NEAT1 knockdown. Also, AKT2 was increased in HCC tissues. Downregulation of AKT2 was associated with reduced cell proliferation and invasion while increased apoptosis, while overexpression of AKT2 exerted opposite roles. In addition, the expression of miRNA-22-3p displayed an inverse association with NEAT1. miRNA-22-3p mimic and inhibitor suppressed and promoted HCC development, respectively. The luciferase assay revealed that both NEAT1 and AKT2 were direct target genes of miRNA-22-3p. Furthermore, knockdown and overexpression of NEAT1 suppressed and promoted tumor growth in the HCC mouse model, which were abolished by the miRNA-22-3p inhibitor and mimic, respectively.

Conclusion: In conclusion, the results demonstrate that NEAT1 promotes the development of HCC, both in vitro and in vivo, through regulating miRNA-22-3p/AKT2, and provides insight into developing a new strategy for HCC treatment.

Citing Articles

MicroRNAs in Hepatocellular Carcinoma Pathogenesis: Insights into Mechanisms and Therapeutic Opportunities.

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MicroRNA as Key Players in Hepatocellular Carcinoma: Insights into Their Role in Metastasis.

Saadh M, Hussain Q, Alazzawi T, Fahdil A, Athab Z, Yarmukhamedov B Biochem Genet. 2024; .

PMID: 39103713 DOI: 10.1007/s10528-024-10897-0.

Extracellular vesicular lncRNA FAL1 promotes hepatocellular carcinoma cell proliferation and invasion by inducing macrophage M2 polarization.

Lv S, Wang J, Li L J Physiol Biochem. 2023; 79(3):669-682.

PMID: 37147492 DOI: 10.1007/s13105-022-00922-4.

Oncogenic role and potential regulatory mechanism of fatty acid binding protein 5 based on a pan-cancer analysis.

Wang J, Zhao S, Sun J, Wang X, Guan M, Yin J Sci Rep. 2023; 13(1):4060.

PMID: 36906605 PMC: 10008585. DOI: 10.1038/s41598-023-30695-9.

Molecular Interactions of the Long Noncoding RNA NEAT1 in Cancer.

Gu J, Zhang B, An R, Qian W, Han L, Duan W Cancers (Basel). 2022; 14(16).

PMID: 36011001 PMC: 9406559. DOI: 10.3390/cancers14164009.

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