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长链非编码RNA PITPNA-AS1作为一种潜在的诊断标志物和治疗靶点，通过调节miR-448/ROCK1轴促进肝细胞癌进展。

LncRNA PITPNA-AS1 as a Potential Diagnostic Marker and Therapeutic Target Promotes Hepatocellular Carcinoma Progression via Modulating miR-448/ROCK1 Axis.

作者信息

Wang Qing-Fang, Wang Qing-Lin, Cao Ming-Bo

机构信息

Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Department of Pharmacology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Front Med (Lausanne). 2021 May 12;8:668787. doi: 10.3389/fmed.2021.668787. eCollection 2021.

DOI:10.3389/fmed.2021.668787
PMID:34055841
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8149744/
Abstract

Long non-coding RNAs are critical to hepatocellular carcinoma (HCC) developments. LncRNA PITPNA antisense RNA 1 (PITPNA-AS1) is a new regulator in several tumors. However, the mechanism by which PITPNA-AS1 mediates the tumorigenesis of HCC remains unclear. RT-qPCR was used to detect the level of PITPNA-AS1 in HCC specimens and cells. The biological functions of PITPNA-AS1 were explored by several functional experiments and . The binding relationship among PITPNA-AS1, miR-448 and ROCK1 were studied by Luciferase assay and pull-down assays. We found that PITPNA-AS1 expressions were distinctly upregulated in both HCC specimens and cell lines. High PITPNA-AS1 levels were an unfavorable biomarker for patients with HCC. Functionally, knockdown of PITPNA-AS1 suppressed the proliferation, migration and invasion of HCC cells. Mechanistically, PITPNA-AS1 functioned as competing endogenous RNA to increase ROCK1 expressions via sponging miR-448. The newly identified PITPNA-AS/miR-448/ROCK1 axis promoted the oncogenicity of HCC cells. This novel axis is likely to be a promising HCC therapeutic aim.

摘要

长链非编码RNA对肝细胞癌（HCC）的发展至关重要。LncRNA磷脂酰肌醇转运蛋白α（PITPNA）反义RNA 1（PITPNA-AS1）是几种肿瘤中的一种新调节因子。然而，PITPNA-AS1介导HCC肿瘤发生的机制仍不清楚。采用逆转录定量聚合酶链反应（RT-qPCR）检测HCC标本和细胞中PITPNA-AS1的水平。通过多项功能实验探讨了PITPNA-AS1的生物学功能。通过荧光素酶报告基因检测和下拉实验研究了PITPNA-AS1、miR-448和ROCK1之间的结合关系。我们发现，PITPNA-AS1在HCC标本和细胞系中的表达均明显上调。高PITPNA-AS1水平对HCC患者来说是一个不良生物标志物。在功能上，敲低PITPNA-AS1可抑制HCC细胞的增殖、迁移和侵袭。从机制上讲，PITPNA-AS1作为竞争性内源RNA，通过结合miR-448来增加ROCK1的表达。新发现的PITPNA-AS/miR-448/ROCK1轴促进了HCC细胞的致癌性。这一新型轴可能是一个有前景的HCC治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917b/8149744/a4d4eedc2307/fmed-08-668787-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917b/8149744/d3039eda1511/fmed-08-668787-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917b/8149744/6ad3a48fc01a/fmed-08-668787-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917b/8149744/197704852547/fmed-08-668787-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917b/8149744/aa5785e9d4d5/fmed-08-668787-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917b/8149744/071a02bdfcc0/fmed-08-668787-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917b/8149744/a4d4eedc2307/fmed-08-668787-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917b/8149744/d3039eda1511/fmed-08-668787-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917b/8149744/6ad3a48fc01a/fmed-08-668787-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917b/8149744/197704852547/fmed-08-668787-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917b/8149744/aa5785e9d4d5/fmed-08-668787-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917b/8149744/071a02bdfcc0/fmed-08-668787-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917b/8149744/a4d4eedc2307/fmed-08-668787-g0006.jpg

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