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沉默 lncRNA XIST 通过上调 microRNA-132 和下调 PXN 对胃癌细胞表现出抗增殖和促凋亡作用。

Silencing lncRNA XIST exhibits antiproliferative and proapoptotic effects on gastric cancer cells by up-regulating microRNA-132 and down-regulating PXN.

机构信息

Department of General Surgery, Huaian Tumor Hospital, Huaian Hospital of Huaian City, Huaian, 223200, P.R. China.

Department of Experimental Surgery-Cancer Metastasis, Medical Faculty Mannheim, Ruprecht Karls University, Mannheim 68167, Germany.

出版信息

Aging (Albany NY). 2020 Nov 5;13(10):14469-14481. doi: 10.18632/aging.103635.

DOI:10.18632/aging.103635
PMID:33154189
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8202840/
Abstract

The present study aims to elucidate the potential therapeutic role of lncRNA XIST in gastric cancer through regulation of microRNA-132 (miR-132) and paxillin (PXN) expression. The study employed 65 gastric cancer tissue specimens and SGC7901 cell lines. Our results demonstrated that expression of lncRNA XIST and PXN was significantly elevated while the expression of miR-132 was significantly reduced in gastric cancer tissues. Dual-luciferase, RNA pull-down and RIP assays demonstrated that lncRNA XIST up-regulated the PXN expression by competitively binding to miR-132. Moreover, silencing of lncRNA XIST and up-regulation of miR-132 could suppress tumor formation ability, cell proliferation and migration, but enhanced apoptosis in gastric cancer. However, the overexpression of PXN achieved the opposite tumor-promotive effect. Meanwhile, rescue experiments suggested that silencing of lncRNA XIST could reverse the tumor-promotive effect exerted by either miR-132 inhibitor or PXN. Taken together, the present study demonstrates lncRNA XIST as a novel oncogenic lncRNA in gastric cancer, highlighting its therapeutic role in this disease.

摘要

本研究旨在通过调节 microRNA-132（miR-132）和桩蛋白（PXN）的表达，阐明长非编码 RNA XIST 在胃癌中的潜在治疗作用。该研究采用了 65 例胃癌组织标本和 SGC7901 细胞系。我们的结果表明，lncRNA XIST 和 PXN 的表达在胃癌组织中显著升高，而 miR-132 的表达显著降低。双荧光素酶报告基因、RNA 下拉和 RIP 实验表明，lncRNA XIST 通过与 miR-132 竞争结合来上调 PXN 的表达。此外，沉默 lncRNA XIST 和上调 miR-132 可以抑制胃癌的肿瘤形成能力、细胞增殖和迁移，但促进细胞凋亡。然而，PXN 的过表达则产生相反的促肿瘤作用。同时，挽救实验表明，沉默 lncRNA XIST 可以逆转 miR-132 抑制剂或 PXN 所发挥的促肿瘤作用。综上所述，本研究表明 lncRNA XIST 是胃癌中的一种新型致癌 lncRNA，强调了其在该疾病中的治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f38/8202840/b52794d14c57/aging-13-103635-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f38/8202840/075a0ed89e35/aging-13-103635-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f38/8202840/914222f94840/aging-13-103635-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f38/8202840/27765580b655/aging-13-103635-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f38/8202840/eb2174386c0c/aging-13-103635-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f38/8202840/b52794d14c57/aging-13-103635-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f38/8202840/075a0ed89e35/aging-13-103635-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f38/8202840/914222f94840/aging-13-103635-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f38/8202840/27765580b655/aging-13-103635-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f38/8202840/eb2174386c0c/aging-13-103635-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f38/8202840/b52794d14c57/aging-13-103635-g005.jpg

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