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YWHAB受IRX5调控,并抑制乳腺癌细胞的迁移和侵袭。

YWHAB is regulated by IRX5 and inhibits the migration and invasion of breast cancer cells.

作者信息

Geng Xuexia, Yuan Jun, Xu Wenjie, Zou Deng, Sun Yuxuan, Li Jun

机构信息

School of Life Science, Huaibei Normal University, Huaibei, Anhui 235000, P.R. China.

出版信息

Oncol Lett. 2024 Jul 31;28(4):469. doi: 10.3892/ol.2024.14602. eCollection 2024 Oct.

Abstract

Highly metastatic and heterogeneous breast cancer affects the health of women worldwide. Abnormal expression of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein β (YWHAB), also known as 14-3-3β, is associated with the tumorigenesis and progression of bladder cancer, lung cancer and hepatocellular carcinoma; however, to the best of our knowledge, the role of in breast cancer remains unknown. In the present study, a dual luciferase assay demonstrated that the transcription factor iroquois homeobox 5 may regulate expression by affecting the promoter sequence upstream of its transcription start site. Subsequently, it was demonstrated that overexpression of did not affect proliferation, but did reduce the migration and invasion of MDA-MB-231 cells. Furthermore, knockdown of promoted the migration and invasion of MCF7 cells. Transcriptomics analysis demonstrated that when was overexpressed, 61 genes were differentially expressed, of which 43 genes were upregulated and 18 genes were downregulated. These differentially expressed genes (DEGs) were enriched in cancer-related pathways, such as 'TNF signaling pathway' [Kyoto Encyclopedia of Genes and Genomes (KEGG): map04688]. The pathway with the largest number of DEGs was 'Rheumatoid arthritis' (KEGG: map05323). Notably, downregulated vimentin, which is a mesenchymal marker, thus suggesting that it may weaken the mesenchymal properties of cells. These findings indicate that may be a potential therapeutic target in breast cancer and further work should be performed to assess its actions as a potential tumor suppressor.

摘要

高转移性和异质性乳腺癌影响着全球女性的健康。酪氨酸3-单加氧酶/色氨酸5-单加氧酶激活蛋白β(YWHAB,也称为14-3-3β)的异常表达与膀胱癌、肺癌和肝细胞癌的肿瘤发生及进展相关;然而,据我们所知,其在乳腺癌中的作用仍不清楚。在本研究中,双荧光素酶报告基因检测表明,转录因子易洛魁同源盒5可能通过影响其转录起始位点上游的启动子序列来调节YWHAB的表达。随后,研究表明YWHAB的过表达不影响增殖,但确实降低了MDA-MB-231细胞的迁移和侵袭能力。此外,敲低YWHAB可促进MCF7细胞的迁移和侵袭。转录组学分析表明,当YWHAB过表达时,有61个基因差异表达,其中43个基因上调,18个基因下调。这些差异表达基因(DEGs)富集于癌症相关通路,如“TNF信号通路”[京都基因与基因组百科全书(KEGG):map04688]。差异表达基因数量最多的通路是“类风湿性关节炎”(KEGG:map05323)。值得注意的是,YWHAB下调了作为间充质标志物的波形蛋白,因此表明它可能会削弱细胞的间充质特性。这些发现表明,YWHAB可能是乳腺癌的一个潜在治疗靶点,应进一步开展工作以评估其作为潜在肿瘤抑制因子的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2849/11306988/5b1a4f0820e4/ol-28-04-14602-g00.jpg

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