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长链非编码RNA PTPRG-AS1通过增强YWHAG促进肝细胞癌转移。

LncRNA PTPRG-AS1 Promotes the Metastasis of Hepatocellular Carcinoma by Enhancing YWHAG.

作者信息

Chen Gaoyang, Zhang Zhisheng, Li Yan, Wang Lu, Liu Yanqing

机构信息

The First Clinical Medical College of Nanjing University of Traditional Chinese Medicine, Nanjing, Jiangsu 210023, China.

Oncology Department, The Second People's Hospital of Taizhou City, Taizhou, Jiangsu 225511, China.

出版信息

J Oncol. 2021 Nov 28;2021:3624306. doi: 10.1155/2021/3624306. eCollection 2021.

DOI:10.1155/2021/3624306
PMID:34876904
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8645374/
Abstract

OBJECTIVES

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. LncRNA PTPRG-AS1 (PTPRG-AS1) has been confirmed to function as a regulator in various cancers, whose function during HCC tumorigenesis is still not clear now. Thus, we aim to dig out the biological function and its mechanisms of PTPRG-AS1 in HCC.

METHODS

PTPRG-AS1 relative expression in tissues and cells was detected and analyzed using real-time quantitative PCR (qRT-PCR). Subcellular distribution of PTPRG-AS1 was examined by FISH experiments. The effects of PTPRG-AS1 in the growth of HCC were studied by in vitro CCK-8 experiments, transwell invasion experiments, and in vivo xenograft tumor experiments. Dual-Luciferase reporter assay was performed to verify the interaction between PTPRG-AS1 and miR-199a-3p or miR-199a-3p and its target gene, YWHAG.

RESULTS

PTPRG-AS1 was upregulated in HCC tissues compared with adjacent normal tissues. We identified PTPRG-AS1 mainly localized in the cytoplasm of HCC cells. Downregulation of PTPRG-AS1 suppressed HCC progression, while overexpression of PTPRG-AS1 showed the opposite effects. Furthermore, PTPRG-AS1 served as a miR-199a-3p sponge and positively regulated YWHAG expression. Besides, PTPRG-AS1 could promote HCC through miR-199a-3p/YWHAG axis.

CONCLUSIONS

Taken together, we demonstrated PTPRG-AS1 may serve as a ceRNA and reversely regulates the expression of miR-199a-3p, thus facilitating HCC tumorigenesis and metastasis, which is expected to provide new clues for the treatment of HCC.

摘要

目的

肝细胞癌（HCC）是最常见的恶性肿瘤之一。长链非编码RNA PTPRG-AS1（PTPRG-AS1）已被证实可在多种癌症中发挥调节作用，但其在HCC肿瘤发生过程中的作用目前仍不清楚。因此，我们旨在探究PTPRG-AS1在HCC中的生物学功能及其机制。

方法

采用实时定量PCR（qRT-PCR）检测并分析组织和细胞中PTPRG-AS1的相对表达。通过荧光原位杂交（FISH）实验检测PTPRG-AS1的亚细胞分布。通过体外CCK-8实验、Transwell侵袭实验和体内异种移植肿瘤实验研究PTPRG-AS1对HCC生长的影响。进行双荧光素酶报告基因检测以验证PTPRG-AS1与miR-199a-3p或miR-199a-3p与其靶基因YWHAG之间的相互作用。

结果

与相邻正常组织相比，PTPRG-AS1在HCC组织中上调。我们发现PTPRG-AS1主要定位于HCC细胞的细胞质中。PTPRG-AS1的下调抑制了HCC的进展，而PTPRG-AS1的过表达则显示出相反的效果。此外，PTPRG-AS1作为miR-199a-3p的海绵，正向调节YWHAG的表达。此外，PTPRG-AS1可通过miR-199a-3p/YWHAG轴促进HCC。

结论

综上所述，我们证明PTPRG-AS1可能作为一种竞争性内源RNA（ceRNA），反向调节miR-199a-3p的表达，从而促进HCC的肿瘤发生和转移，有望为HCC的治疗提供新线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0d3/8645374/b73f8d93c229/JO2021-3624306.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0d3/8645374/a6ca1610f11c/JO2021-3624306.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0d3/8645374/f47d3cd7f6c8/JO2021-3624306.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0d3/8645374/e48f6951a352/JO2021-3624306.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0d3/8645374/2c3d183667b7/JO2021-3624306.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0d3/8645374/1f1f5aa67d6a/JO2021-3624306.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0d3/8645374/b73f8d93c229/JO2021-3624306.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0d3/8645374/a6ca1610f11c/JO2021-3624306.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0d3/8645374/f47d3cd7f6c8/JO2021-3624306.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0d3/8645374/e48f6951a352/JO2021-3624306.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0d3/8645374/2c3d183667b7/JO2021-3624306.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0d3/8645374/1f1f5aa67d6a/JO2021-3624306.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c0d3/8645374/b73f8d93c229/JO2021-3624306.006.jpg

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