YY1 诱导 FAM111B 的转录激活促进乳腺癌的恶性进展。

YY1-Induced Transcriptional Activation of FAM111B Contributes to the Malignancy of Breast Cancer.

机构信息

Department of General surgery, Inner Mongolia Baogang Hospital, Inner Mongolia, P.R. China.

出版信息

Clin Breast Cancer. 2022 Jun;22(4):e417-e425. doi: 10.1016/j.clbc.2021.10.008. Epub 2021 Oct 29.

DOI:10.1016/j.clbc.2021.10.008

PMID:34802969

Abstract

BACKGROUND

Family with sequence similarity 111 member B (FAM111B) is an oncoprotein associated with multiple malignancies. We investigated the potential mechanisms of FAM111B in breast cancer.

PATIENTS AND METHODS

We tested the expression of FAM111B in breast cancer tissues and the survival rate of breast cancer patients with high or low level of FAM111B through TCGA data. The expression of FAM111B in breast cancer tissues and adjacent tissues was detected using western blotting. Then we used siRNA to construct a low expression model of FAM111B in SKBR3 and MDA-MB-468. EdU, CCK-8, wound healing, and transwell assays were performed to monitor the proliferation, migration, and invasion of breast cancer cells. Western blotting was used to detect the expression of EMT-related indicators. Chromatin Immunoprecipitation (ChIP) and qPCR were used to evaluate the regulatory effect of Yin Yang 1 (YY1) on FAM111B.

RESULTS

The expression of FAM111B in breast cancer tissues was higher than that in normal tissues. Patients who had high FAM111B expression had a worse prognosis. Knockdown of FAM111B inhibited the proliferation, migration, and invasion of breast cancer cells. Knockdown of FAM111B resulted in increased expression of EMT-related protein E-cadherin and decreased expression of N-cadherin and Vimentin. ChIP-qPCR analysis demonstrated that YY1 could bind to the promoter of FAM111B gene and strengthen its transcription activity.

CONCLUSION

YY1-induced transcriptional activation of FAM111B accelerated the progression of breast cancer.

摘要

背景

家族序列相似性 111 成员 B（FAM111B）是一种与多种恶性肿瘤相关的癌蛋白。我们研究了 FAM111B 在乳腺癌中的潜在机制。

患者和方法

我们通过 TCGA 数据检测了乳腺癌组织中 FAM111B 的表达以及高或低 FAM111B 水平的乳腺癌患者的生存率。使用 Western blot 检测乳腺癌组织和相邻组织中 FAM111B 的表达。然后，我们使用 siRNA 构建 SKBR3 和 MDA-MB-468 中 FAM111B 低表达模型。EdU、CCK-8、划痕愈合和 Transwell 测定用于监测乳腺癌细胞的增殖、迁移和侵袭。Western blot 用于检测 EMT 相关指标的表达。染色质免疫沉淀（ChIP）和 qPCR 用于评估 Yin Yang 1（YY1）对 FAM111B 的调控作用。

结果

乳腺癌组织中 FAM111B 的表达高于正常组织。FAM111B 高表达的患者预后较差。FAM111B 敲低抑制了乳腺癌细胞的增殖、迁移和侵袭。FAM111B 敲低导致 EMT 相关蛋白 E-钙粘蛋白表达增加，N-钙粘蛋白和波形蛋白表达减少。ChIP-qPCR 分析表明，YY1 可以结合 FAM111B 基因的启动子并增强其转录活性。