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抑制素 β-A(INHBA)通过激活 TGF-β 信号通路诱导上皮-间充质转化并加速乳腺癌细胞的迁移。

Inhibin β-A (INHBA) induces epithelial-mesenchymal transition and accelerates the motility of breast cancer cells by activating the TGF-β signaling pathway.

机构信息

Department of Obstetrics and Gynecology, the International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P. R. China.

Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China.

出版信息

Bioengineered. 2021 Dec;12(1):4681-4696. doi: 10.1080/21655979.2021.1957754.

DOI:10.1080/21655979.2021.1957754
PMID:34346300
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8806747/
Abstract

Accumulating evidence indicates that INHBA (Inhibin β-A, a member of the TGF-β superfamily) functions as an oncogene in cancer progression. However, little is known as to how INHBA regulates the progression and aggressiveness of breast cancer (BC). This study explored the function and underlying mechanism of INHBA in epithelial-mesenchymal transition (EMT) of BC cells. INHBA expression in BC cell lines was measured using RT-qPCR and Western blot. The would-healing and transwell migration assays were used to investigate the effect of INHBA overexpression or silencing on BC cell motility. Moreover, the expression levels of EMT-related genes were quantified after overexpressing or silencing of INHBA. Based on published dataset, INHBA was significantly upregulated in BC tissues compared to the adjacent normal tissues. A higher level of INHBA expression was also correlated with a poor survival in BC patients. In addition, study showed that INHBA played an indispensable role in promoting BC cell proliferation and invasion. Mechanistically, INHBA induced epithelial-mesenchymal transition (EMT) and accelerated the motility of BC cells by activating TGF-β-regulated genes. In conclusion, INHBA plays a functional role in supporting EMT phenotype of BC cells, and it may serve as a diagnostic biomarker and a potential therapeutic target for BC treatment.

摘要

越来越多的证据表明,INHBA(转化生长因子-β 超家族的一员)在癌症进展中作为癌基因发挥作用。然而,关于 INHBA 如何调节乳腺癌(BC)的进展和侵袭性,目前知之甚少。本研究探讨了 INHBA 在 BC 细胞上皮-间充质转化(EMT)中的功能和潜在机制。使用 RT-qPCR 和 Western blot 测量 BC 细胞系中的 INHBA 表达。使用伤口愈合和 Transwell 迁移实验来研究 INHBA 过表达或沉默对 BC 细胞迁移的影响。此外,在过表达或沉默 INHBA 后,定量 EMT 相关基因的表达水平。基于已发表的数据集,与相邻正常组织相比,BC 组织中 INHBA 的表达显著上调。较高水平的 INHBA 表达也与 BC 患者的不良生存相关。此外,研究表明 INHBA 在促进 BC 细胞增殖和侵袭中发挥不可或缺的作用。在机制上,INHBA 通过激活 TGF-β 调节的基因诱导 EMT,并加速 BC 细胞的迁移。总之,INHBA 在支持 BC 细胞 EMT 表型中发挥功能作用,它可能作为 BC 治疗的诊断生物标志物和潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba3/8806747/bc23def96e6d/KBIE_A_1957754_F0008_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba3/8806747/cdd366c52a1e/KBIE_A_1957754_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba3/8806747/318e2925f893/KBIE_A_1957754_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba3/8806747/d896aefe753d/KBIE_A_1957754_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba3/8806747/580cc866d342/KBIE_A_1957754_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba3/8806747/de7cbcc6d0f8/KBIE_A_1957754_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba3/8806747/17892261a351/KBIE_A_1957754_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba3/8806747/7f716e150d59/KBIE_A_1957754_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba3/8806747/bc23def96e6d/KBIE_A_1957754_F0008_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba3/8806747/cdd366c52a1e/KBIE_A_1957754_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba3/8806747/318e2925f893/KBIE_A_1957754_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba3/8806747/d896aefe753d/KBIE_A_1957754_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba3/8806747/580cc866d342/KBIE_A_1957754_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba3/8806747/de7cbcc6d0f8/KBIE_A_1957754_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba3/8806747/17892261a351/KBIE_A_1957754_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba3/8806747/7f716e150d59/KBIE_A_1957754_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cba3/8806747/bc23def96e6d/KBIE_A_1957754_F0008_OC.jpg

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