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长链非编码 RNA TMEM147-AS1 通过吸附 microRNA-326 而上调 SMAD5 加剧胃癌的恶性程度。

Long noncoding RNA TMEM147-AS1 serves as a microRNA-326 sponge to aggravate the malignancy of gastric cancer by upregulating SMAD5.

机构信息

Second Department of Gastroenterology, Heilongjiang Provincial Hospital, Harbin, 150001, China.

Department of General Medicine, Heilongjiang Provincial Hospital, Harbin, 150001, China.

出版信息

Oncol Res. 2022 Aug 31;29(4):263-273. doi: 10.32604/or.2022.03568. eCollection 2021.

DOI:10.32604/or.2022.03568
PMID:37303938
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10208078/
Abstract

The abnormal expression of long noncoding RNAs (lncRNAs) is frequently observed in gastric cancer (GC) and considered an important driving force in GC progression. However, little is known regarding the involvement of TMEM147-AS1 in GC. Therefore, we examined TMEM147-AS1 expression in GC and determined its prognostic value. In addition, TMEM147-AS1 expression was depleted to identify the functional changes in response to TMEM147-AS1 deficiency. Using the cancer genome atlas dataset and our own cohort, we identified a strong expression of TMEM147-AS1 in GC. Increased TMEM147-AS1 levels in GC showed a significant association with poor prognosis. TMEM147-AS1 interference resulted in the inhibition of GC cell proliferation, colony-forming, migration, and invasion . Additionally, depletion of TMEM147-AS1 restricted the growth of GC cells . Mechanistically, TMEM147-AS1 functioned as a microRNA-326 (miR-326) sponge. Furthermore, SMAD family member 5 (SMAD5) was experimentally validated as the functional effector of miR-326. TMEM147-AS1 was demonstrated to sequester miR-326 away from SMAD5; consequently, knocking down TMEM147-AS1 downregulated SMAD5 levels in GC cells. The functional suppression of miR-326 or reintroduction of SMAD5 effectively reversed the attenuated behavior of GC cells caused by TMEM147-AS1 downregulation. In summary, TMEM147-AS1 exhibits tumorigenic activities in GC, which is likely the result of an altered miR-326/SMAD5 axis. Therefore, targeting TMEM147-AS1/miR-326/SMAD5 may represent a target for the treatment of GC.

摘要

长链非编码 RNA（lncRNA）的异常表达在胃癌（GC）中经常观察到，并被认为是 GC 进展的重要驱动因素。然而，关于 TMEM147-AS1 在 GC 中的参与知之甚少。因此，我们检查了 GC 中 TMEM147-AS1 的表达，并确定了其预后价值。此外，我们通过耗尽 TMEM147-AS1 来识别 TMEM147-AS1 缺乏对功能变化的影响。使用癌症基因组图谱数据集和我们自己的队列，我们确定了 TMEM147-AS1 在 GC 中的强烈表达。GC 中 TMEM147-AS1 水平的升高与预后不良显著相关。TMEM147-AS1 干扰导致 GC 细胞增殖、集落形成、迁移和侵袭受到抑制。此外，TMEM147-AS1 的耗竭限制了 GC 细胞的生长。在机制上，TMEM147-AS1 作为 microRNA-326（miR-326）的海绵起作用。此外，SMAD 家族成员 5（SMAD5）被实验验证为 miR-326 的功能效应物。TMEM147-AS1 被证明可以将 miR-326 从 SMAD5 上隔离出来；因此，敲低 TMEM147-AS1 会降低 GC 细胞中的 SMAD5 水平。miR-326 的功能抑制或 SMAD5 的重新引入有效地逆转了 TMEM147-AS1 下调导致的 GC 细胞减弱行为。总之，TMEM147-AS1 在 GC 中表现出致癌活性，这可能是改变的 miR-326/SMAD5 轴的结果。因此，靶向 TMEM147-AS1/miR-326/SMAD5 可能代表治疗 GC 的一种方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/1c43ed36b16b/OncolRes-29-3568-f011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/148ec67a38dc/OncolRes-29-3568-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/0df7bb40e024/OncolRes-29-3568-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/471053871ad1/OncolRes-29-3568-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/5a5ec00129ec/OncolRes-29-3568-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/d9996f1645e1/OncolRes-29-3568-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/ccb8e2bdbddd/OncolRes-29-3568-f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/688c96f13d41/OncolRes-29-3568-f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/739df7563516/OncolRes-29-3568-f008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/dd858f6badfd/OncolRes-29-3568-f009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/8fcddf908e12/OncolRes-29-3568-f010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/1c43ed36b16b/OncolRes-29-3568-f011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/148ec67a38dc/OncolRes-29-3568-f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/0df7bb40e024/OncolRes-29-3568-f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/471053871ad1/OncolRes-29-3568-f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/5a5ec00129ec/OncolRes-29-3568-f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/d9996f1645e1/OncolRes-29-3568-f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/ccb8e2bdbddd/OncolRes-29-3568-f006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/688c96f13d41/OncolRes-29-3568-f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/739df7563516/OncolRes-29-3568-f008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/dd858f6badfd/OncolRes-29-3568-f009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/8fcddf908e12/OncolRes-29-3568-f010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5905/10208078/1c43ed36b16b/OncolRes-29-3568-f011.jpg

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引用本文的文献

[1]
Clinical Significance and Immune Infiltration Analyses of a Novel Nerve-Related lncRNA Signature in Gastric Cancer.

Mol Biotechnol. 2025-1

[2]
SMAD Proteins in TGF-β Signalling Pathway in Cancer: Regulatory Mechanisms and Clinical Applications.

Diagnostics (Basel). 2023-8-26

本文引用的文献

[1]
Regulatory RNAs, microRNA, long-non coding RNA and circular RNA roles in colorectal cancer stem cells.

World J Gastrointest Oncol. 2022-4-15

[2]
LncRNA CRART16/miR-122-5p/FOS axis promotes angiogenesis of gastric cancer by upregulating VEGFD expression.

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Silencing of long non-coding RNA HCP5 inhibits proliferation, invasion, migration, and promotes apoptosis via regulation of miR-299-3p/SMAD5 axis in gastric cancer cells.

Bioengineered. 2021-12

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