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INHBA 基因沉默通过阻碍 TGF-β 信号通路的激活抑制胃癌细胞迁移和侵袭。

INHBA gene silencing inhibits gastric cancer cell migration and invasion by impeding activation of the TGF-β signaling pathway.

机构信息

Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.

Department of Intestinal Surgery, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, People's Republic of China.

出版信息

J Cell Physiol. 2019 Aug;234(10):18065-18074. doi: 10.1002/jcp.28439. Epub 2019 Apr 8.

Abstract

Gastric cancer (GC) is the fourth largest cancer in the world, with a 5-year survival rate of <30%. Thus, this study intends to investigate the effects of inhibin βA (INHBA) gene silencing on the migration and invasion of GC cells via the transforming growth factor-β (TGF-β) signaling pathway. Initially, this study determined the expression of INHBA and the TGF-β signaling pathway-related genes in GC tissues. After that, to assess the effect of INHBA silencing on GC progression, GC cells were transfected with short hairpin RNAs that targeted INHBA in order to detect the expression of INHBA and the TGF-β signaling pathway-related genes, as well as cell migration, invasion, and proliferation abilities. Finally, a tumor xenograft model in nude mice was constructed to verify the effect that the silencing of INHBA had on tumor growth. Highly expressed INHBA and activated TGF-β signaling pathways were observed in GC tissues. In response to shINHBA-1 and shINHBA-2, the TGF-β signaling pathway was inhibited in GC cells, whereas the GC cell migration, invasion, proliferation, and tumor growth were significantly dampened. On the basis of the observations and findings of this study, INHBA gene silencing inhibited the progression of GC by inactivating the TGF-β signaling pathway, which provides a potential target in the treatment of GC.

摘要

胃癌(GC)是全球第四大癌症,5 年生存率<30%。因此,本研究旨在通过转化生长因子-β(TGF-β)信号通路研究抑制素βA(INHBA)基因沉默对 GC 细胞迁移和侵袭的影响。本研究首先确定了 GC 组织中 INHBA 和 TGF-β 信号通路相关基因的表达。之后,为了评估 INHBA 沉默对 GC 进展的影响,用靶向 INHBA 的短发夹 RNA 转染 GC 细胞,以检测 INHBA 和 TGF-β 信号通路相关基因的表达,以及细胞迁移、侵袭和增殖能力。最后,构建裸鼠肿瘤异种移植模型,以验证 INHBA 沉默对肿瘤生长的影响。GC 组织中观察到 INHBA 高表达和 TGF-β 信号通路激活。在 shINHBA-1 和 shINHBA-2 作用下,GC 细胞中 TGF-β 信号通路被抑制,而 GC 细胞迁移、侵袭、增殖和肿瘤生长明显受到抑制。基于本研究的观察和发现,INHBA 基因沉默通过使 TGF-β 信号通路失活来抑制 GC 的进展,为 GC 的治疗提供了一个潜在的靶点。

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