<p>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</p>

Abstract

BackgroundHepatocellular 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.ObjectiveIn this study, we elucidated the effect of long noncoding RNA (lncRNA) NEAT1 on HCC development and underlying mechanisms.MethodsClinicopathological 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.ResultsThe 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.ConclusionIn 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.

<p>Exosomal MicroRNAs as Liquid Biopsy Biomarkers in Hepatocellular Carcinoma</p>

“…This group of microRNAs has been extensively studied and has been shown to be downregulated in several cancers, such as gastric cancer, peripheral nerve sheath tumors, esophageal squamous cell carcinoma, melanoma, and breast cancer, among others. 13,34 In these diseases, the increased expression of miR-21 leads to the up-regulation of its downstream targets that are involved in epigenetic modification, metastasis and cell proliferation. 34 miRNA-96 could repress the cancer cell growth and migration respectively in a previous study.…”

“…13,34 In these diseases, the increased expression of miR-21 leads to the up-regulation of its downstream targets that are involved in epigenetic modification, metastasis and cell proliferation. 34 miRNA-96 could repress the cancer cell growth and migration respectively in a previous study. Furthermore, miRNA-96 expression was reduced in endometrioid adenocarcinoma, papillary thyroid carcinoma, ovarian cancer and hepatocellular carcinoma.…”

LncRNANEAT1: Shedding light on mechanisms and opportunities in liver diseases

“…It has been reported that AKT2 is overexpressed in HCC and independently correlated with the prognosis of human HCC 78 . In particular, a study by Zhou et al revealed that NEAT1 positively regulated AKT2 expression by inhibiting miR‐22‐3p, thus, promoting HCC development 79 . Liu et al found that NEAT1 reduced apoptosis and promoted the proliferation of HepG2/Huh7 cells by sponging miR‐let‐7b, thereby emancipating the downstream signalling of insulin‐like growth factor type 1 receptor (IGF‐1R) 80 .…”

Long Non-Coding RNAs in Liver Cancer and Nonalcoholic Steatohepatitis

“…Since 2019, there have been four studies reporting its function as a miRNA sponge in the liver by binding to miR-9-5p, miR-21, miR-26b-5p, and miR-214, which target SRY-box transcription factor 11 (SOX11) [50], LDL receptor related protein 6 (LRP6) [51], platelet derived growth factor receptor beta (PDGFRB) [52], and activating transcription factor 4 (ATF4) [53] mRNAs, respectively. Another well-known miRNA sponge, the nuclear paraspeckle assembly transcript 1 (NEAT1) [54] with nine isoforms (ENSG00000245532) with the longest isoform being 22,743 nt (ENST00000501122), binds to let-7a, miR-22-3p, miR-29b, miR-140, miR-146a-5p, miR-155, miR-335, and miR-506 [55][56][57][58][59][60][61][62]. With an lncRNA having many isoforms, the research questions should focus on the identification of isoform-specific function of miRNA sponges, as it is experimentally very challenging to overexpress an isoform with over 10,000 nt in a stable manner.…”