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长链非编码 RNA MYOSLID 通过海绵吸附 miR-29c-3p 作为竞争性内源性 RNA 调节胃癌中 MCL-1 的表达。

Long non-coding RNA MYOSLID functions as a competing endogenous RNA to regulate MCL-1 expression by sponging miR-29c-3p in gastric cancer.

机构信息

Laboratory of Tissue Engineering, Faculty of Life Science, Northwest University, Xi'an, China.

State key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Military Medical University, Xi'an, China.

出版信息

Cell Prolif. 2019 Nov;52(6):e12678. doi: 10.1111/cpr.12678. Epub 2019 Sep 9.

Abstract

OBJECTIVE

Long non-coding RNA (lncRNA) has become an important regulator of many human malignancies. However, the biological role and clinical significance of most lncRNA in gastric cancer (GC) remain unclear.

METHODS

We investigate the biological function, mechanism of action and clinical expression of lncRNA MYOSLID in GC. First, we analysed the differential expression of lncRNA MYOSLID in GC tissues and non-cancerous tissues by analysing the sequencing data obtained from The Cancer Genome Atlas. Subsequently, we verified that lncRNA MYOSLID regulates the proliferation and apoptosis of GC cells by acting as a ceRNA against miR-29c-3p. The nude mouse xenograft was used to further confirm the functional significance of lncRNA MYOSLID in vivo.

RESULTS

We found for the first time that the expression of lncRNA MYOSLID was significantly up-regulated in GC tissues, and the up-regulation of lncRNA MYOSLID in GC was correlated with tumour size, AJCC stage, depth of invasion and survival time. In addition, apoptosis and growth arrest can be induced in vitro after knockdown of lncRNA MYOSLID, which inhibits tumorigenesis in mouse xenografts in vivo. Further in-depth studies revealed that lncRNA MYOSLID acts as a ceRNA of miR-29c-3p, resulting in de-repression of its downstream target gene MCL-1.

CONCLUSION

The lncRNA MYOSLID-miR-29c-3p-MCL-1 axis plays a key role in the development of GC. Our findings may provide potential new targets for the diagnosis and treatment of human GC.

摘要

目的

长链非编码 RNA(lncRNA)已成为许多人类恶性肿瘤的重要调控因子。然而,大多数 lncRNA 在胃癌(GC)中的生物学功能和临床意义仍不清楚。

方法

我们研究了 lncRNA MYOSLID 在 GC 中的生物学功能、作用机制和临床表达。首先,我们通过分析来自癌症基因组图谱的测序数据来分析 GC 组织和非癌组织中 lncRNA MYOSLID 的差异表达。随后,我们验证了 lncRNA MYOSLID 通过作为 miR-29c-3p 的 ceRNA 来调节 GC 细胞的增殖和凋亡。裸鼠异种移植进一步证实了 lncRNA MYOSLID 在体内的功能意义。

结果

我们首次发现 lncRNA MYOSLID 在 GC 组织中的表达明显上调,GC 中 lncRNA MYOSLID 的上调与肿瘤大小、AJCC 分期、浸润深度和生存时间相关。此外,体外敲低 lncRNA MYOSLID 可诱导细胞凋亡和生长停滞,并抑制体内小鼠异种移植中的肿瘤发生。进一步深入研究表明,lncRNA MYOSLID 作为 miR-29c-3p 的 ceRNA,导致其下游靶基因 MCL-1 的去抑制。

结论

lncRNA MYOSLID-miR-29c-3p-MCL-1 轴在 GC 的发生发展中起关键作用。我们的研究结果可能为人类 GC 的诊断和治疗提供潜在的新靶点。

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