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Knockdown of TRIM47 inhibits breast cancer tumorigenesis and progression through the inactivation of PI3K/Akt pathway.
Chemico-Biological Interactions ( IF 4.7 ) Pub Date : 2020-01-22 , DOI: 10.1016/j.cbi.2020.108960
Yaqiu Wang 1 , Can Liu 1 , Zhihui Xie 1 , Hong Lu 1
Affiliation  

Tripartite motif (TRIM) protein family is a group of proteins, which belongs to RING family of ubiquitin E3 ligases. TRIM proteins are involved in oncogenesis, while the roles in different cancers are controversial. However, the expression pattern and biological functions of TRIM47 in breast cancer remain unclear. In the present study, we aimed to investigate the function of TRIM47 in the progression and metastasis of breast cancer. TRIM47 was found to be significantly up-regulated in breast cancer tissues and cell lines. TRIM47 knockdown in breast cancer cell lines significantly inhibited cell proliferation, migration, and invasion. Besides, TRIM47 knockdown regulated the expressions of the epithelial-mesenchymal transition (EMT)-related markers including increase in E-cadherin, and decrease in N-cadherin, vimentin and Snail. Xenograft tumor assay proved that TRIM47 knockdown also suppressed tumor growth in vivo. Furthermore, TRIM47 knockdown markedly inhibited the activation of PI3K/Akt signaling pathway, while the effects of TRIM47 knockdown were reversed by the treatment of insulin-like growth factor-1 (IGF-1), which is an activator of PI3K/Akt. Taken together, the findings indicated that knockdown of TRIM47 suppressed tumorigenesis and progression of breast cancer through the inhibition of PI3K/Akt pathway, and suggested that TRIM47 might be a potential therapy target for breast cancer treatment.

中文翻译:

TRIM47的抑制通过PI3K / Akt途径的失活抑制乳腺癌的发生和发展。

三方基序(TRIM)蛋白家族是一组蛋白,属于泛素E3连接酶的RING家族。TRIM蛋白参与肿瘤发生,而在不同癌症中的作用是有争议的。然而,TRIM47在乳腺癌中的表达模式和生物学功能仍不清楚。在本研究中,我们旨在研究TRIM47在乳腺癌的进展和转移中的功能。发现TRIM47在乳腺癌组织和细胞系中显着上调。乳腺癌细胞系中的TRIM47抑制可显着抑制细胞增殖,迁移和侵袭。此外,TRIM47敲低调节上皮-间质转化(EMT)相关标志物的表达,包括E-钙粘蛋白的增加,N-钙粘蛋白,波形蛋白和Snail的减少。异种移植肿瘤试验证明,TRIM47敲低还抑制了体内肿瘤的生长。此外,TRIM47敲低显着抑制了PI3K / Akt信号通路的激活,而TRIM47敲低的作用被作为PI3K / Akt激活剂的胰岛素样生长因子-1(IGF-1)的治疗所逆转。综上所述,发现表明TRIM47的敲低通过抑制PI3K / Akt途径而抑制了乳腺癌的发生和发展,并暗示TRIM47可能是乳腺癌潜在的治疗靶标。是PI3K / Akt的激活剂。综上所述,发现表明TRIM47的敲低通过抑制PI3K / Akt途径而抑制了乳腺癌的发生和发展,并暗示TRIM47可能是乳腺癌潜在的治疗靶标。是PI3K / Akt的激活剂。综上所述,发现表明TRIM47的敲低通过抑制PI3K / Akt途径而抑制了乳腺癌的发生和发展,并暗示TRIM47可能是乳腺癌潜在的治疗靶标。
更新日期:2020-01-22
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