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长链非编码 RNA PSMA3-AS1 通过调控 miR-329-3p/ALDOA 轴发挥竞争性内源 RNA 的作用,促进胃癌的进展。

Long noncoding RNA PSMA3-AS1 functions as a competing endogenous RNA to promote gastric cancer progression by regulating the miR-329-3p/ALDOA axis.

机构信息

Department of Geriatrics, Shengjing Hospital of China Medical University, Shenyang, 110004, China.

Department of Endoscopy, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, China.

出版信息

Biol Direct. 2023 Jul 4;18(1):36. doi: 10.1186/s13062-023-00392-8.

DOI:10.1186/s13062-023-00392-8
PMID:37403106
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10318671/
Abstract

LncRNA PSMA3-AS1 functions as an oncogene in several cancers, including ovarian cancer, lung cancer, and colorectal cancer. However, its role in gastric cancer (GC) progression remains unclear. In this study, the levels of PSMA3-AS1, miR-329-3p, and aldolase A (ALDOA) in 20 paired human GC tissues and adjacent nontumorous tissues were measured by real-time PCR. GC cells were transfected with recombinant plasmid carrying full-length PSMA3-AS1 or shRNA targeting PSMA3-AS1. The stable transfectants were selected by G418. Then, the effects of PSMA3-AS1 knockdown or overexpression on GC progression in vitro and in vivo were evaluated. The results showed that PSMA3-AS1 was highly expressed in human GC tissues. Stable knockdown of PSMA3-AS1 significantly restrained proliferation/migration/invasion, enhanced cell apoptosis, and induced oxidative stress in vitro. Tumor growth and matrix metalloproteinase expression in tumor tissues were markedly inhibited, while oxidative stress was enhanced in nude mice after stable PSMA3-AS1 knockdown. Additionally, PSMA3-AS1 negatively regulated miR-329-3p while positively regulated ALDOA expression. MiR-329-3p directly targeted ALDOA-3'UTR. Interestingly, miR-329-3p knockdown or ALDOA overexpression partially attenuated the tumor-suppressive effects of PSMA3-AS1 knockdown. Conversely, PSMA3-AS1 overexpression exhibited the opposite effects. PSMA3-AS1 promoted GC progression by regulating the miR-329-3p/ALDOA axis. PSMA3-AS1 might serve as a promising and effective target for GC treatment.

摘要

LncRNA PSMA3-AS1 在多种癌症中发挥癌基因作用,包括卵巢癌、肺癌和结直肠癌。然而,其在胃癌(GC)进展中的作用尚不清楚。在这项研究中,通过实时 PCR 测量了 20 对人 GC 组织和相邻非肿瘤组织中 PSMA3-AS1、miR-329-3p 和醛缩酶 A(ALDOA)的水平。GC 细胞用携带全长 PSMA3-AS1 的重组质粒或针对 PSMA3-AS1 的 shRNA 转染。通过 G418 选择稳定转染的细胞。然后,评估 PSMA3-AS1 敲低或过表达对体外和体内 GC 进展的影响。结果表明,PSMA3-AS1 在人 GC 组织中高表达。PSMA3-AS1 的稳定敲低显着抑制了体外增殖/迁移/侵袭,增强了细胞凋亡,并诱导了氧化应激。裸鼠肿瘤组织中肿瘤生长和基质金属蛋白酶表达明显受到抑制,而稳定敲低 PSMA3-AS1 后氧化应激增强。此外,PSMA3-AS1 负调控 miR-329-3p,而正调控 ALDOA 表达。miR-329-3p 直接靶向 ALDOA-3'UTR。有趣的是,miR-329-3p 敲低或 ALDOA 过表达部分减弱了 PSMA3-AS1 敲低的肿瘤抑制作用。相反,PSMA3-AS1 的过表达表现出相反的效果。PSMA3-AS1 通过调节 miR-329-3p/ALDOA 轴促进 GC 进展。PSMA3-AS1 可能成为治疗 GC 的有前途和有效的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5940/10318671/395f8062ec6b/13062_2023_392_Fig9_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5940/10318671/395f8062ec6b/13062_2023_392_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5940/10318671/107fe2b43ffc/13062_2023_392_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5940/10318671/c2ac455f2348/13062_2023_392_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5940/10318671/19875e189d4b/13062_2023_392_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5940/10318671/4fa13fb17fe9/13062_2023_392_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5940/10318671/863230e8efe8/13062_2023_392_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5940/10318671/26317200570e/13062_2023_392_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5940/10318671/6593217584f7/13062_2023_392_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5940/10318671/ee3bac0813c1/13062_2023_392_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5940/10318671/395f8062ec6b/13062_2023_392_Fig9_HTML.jpg

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