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长链非编码 RNA H19 通过 miR-148-3p/SOX-12 轴促进胃癌转移。

LncRNA H19 Promotes Gastric Cancer Metastasis via miR-148-3p/SOX-12 Axis.

机构信息

Department of Orthopedics Shenmu Hospital Faculty of Life Sciences and Medicine Northwest University, Guangming Road, Shenmu 719300, China.

Department of Cardiology Affiliated Hospital Yan'an University, 43 North Street, Yan'an 716000, China.

出版信息

Anal Cell Pathol (Amst). 2024 Aug 17;2024:6217134. doi: 10.1155/2024/6217134. eCollection 2024.

Abstract

BACKGROUND

Gastric cancer (GC) is the most common malignant tumor and ranks third in the world. LncRNA H19 (H19), one of the members of lncRNA, is overexpressed in various tumors. However, many undetermined molecular mechanisms by which H19 promotes GC progression still need to be further investigated. . A series of experiments was used to confirm the undetermined molecular mechanism including wound healing and transwell assays. . In this study, a significant upregulation of H19 expression was detected in GC cells and tissues. The poor overall survival was observed in GC patient with high H19 expression. Overexpression of H19 promoted the migration of GC cells, while knockdown of H19 significantly inhibited cell migration. Moreover, miR-148a-3p had a certain negative correlation with H19. Luciferase reporter assay confirmed that H19 could directly bind to miR-148a-3p. As expected, miR-148a mimics inhibited cell migration and invasion induced by H19 overexpression. The above findings proved that H19 functions as a miRNA sponge and verified that miR-148a-3p is the H19-associated miRNA in GC. We also confirmed that SOX-12 expression was upregulated in GC patient's samples. SOX-12 expression was positively correlated with expression of H19 and was able to directly bind to miR-148a-3p. Importantly, wound healing assay showed that knockout of SOX-12 could reverse the promoting effect of H19 overexpression on cell migration.

CONCLUSION

In conclusion, H19 has certain application value in the diagnosis and prognosis of GC. Specifically, H19 accelerates GCs to migration and metastasis by miR-138a-3p/SOX-12 axis.

摘要

背景

胃癌(GC)是最常见的恶性肿瘤,在全球范围内排名第三。lncRNA H19(H19)是 lncRNA 的成员之一,在各种肿瘤中过度表达。然而,H19 促进 GC 进展的许多不确定的分子机制仍需要进一步研究。. 一系列实验用于证实不确定的分子机制,包括划痕愈合和 Transwell 分析。. 在这项研究中,检测到 GC 细胞和组织中 H19 表达显著上调。H19 高表达的 GC 患者总生存情况较差。H19 的过表达促进了 GC 细胞的迁移,而 H19 的敲低则显著抑制了细胞迁移。此外,miR-148a-3p 与 H19 呈一定的负相关。荧光素酶报告基因实验证实 H19 可直接与 miR-148a-3p 结合。不出所料,miR-148a 模拟物抑制了 H19 过表达诱导的细胞迁移和侵袭。上述发现证明 H19 作为 miRNA 海绵发挥作用,并验证了 miR-148a-3p 是 GC 中与 H19 相关的 miRNA。我们还证实 SOX-12 的表达在 GC 患者的样本中上调。SOX-12 的表达与 H19 的表达呈正相关,并且能够直接与 miR-148a-3p 结合。重要的是,划痕愈合实验表明,SOX-12 的敲除可以逆转 H19 过表达对细胞迁移的促进作用。

结论

总之,H19 在 GC 的诊断和预后中有一定的应用价值。具体来说,H19 通过 miR-138a-3p/SOX-12 轴加速 GC 细胞的迁移和转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ef1/11344645/ffe026a4e234/ACP2024-6217134.001.jpg

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