Li Zi-Xiong, Huang Ze-Nan, Luo Hui, Yang Xiong-Bin, Wang Yu-Lin, Chen Jie-Xin, Ma Xiao-Kai, Xu Feng, Wang Tian-Tian, Lin Ling
Department of Rheumatology, The First Affiliated Hospital, Shantou University Medical College, Shantou, China.
Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Ann Transl Med. 2021 Aug;9(15):1252. doi: 10.21037/atm-21-3409.
Hormone receptor-negative breast cancer (HRNBC), which includes triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER-2) overexpressing breast cancer, is prone to metastasis and has a poor prognosis. BTB/POZ domain-containing protein 7 (Btbd7) is thought to regulate SLUG and the epithelial-mesenchymal transition (EMT) process. However, the role of Btbd7 in HRNBC is unclear.
Expression of BTBD7 and SLUG in HRNBC tumor tissue and normal adjacent tissue (NAT) as well as breast cancer cells were characterized by immunohistochemistry and immunofluorescence. MDA-MA-231 cells was transfected with BTBD7 siRNA and detected by qRT-PCR and western blot. Expression levels of Slug and EMT related proteins were detected western blot analysis. cell invasion assays were used to analyse cell invasion ability of MDA-MA-231. GO and KEGG analyses was used to analysis the gene function.
The total positive rate of BTBD7 expression in HRNBC tumor tissue was 66.7%, which was higher than that in NAT (52.1%) and benign breast lesion tissues (20%). Co-expression of SLUG and BTBD7 proteins could be found in HRNBC tissue and MDA-MA-231 cells. silencing significantly up-regulated the epithelial marker E-cadherin, down-regulated the mesenchymal markers α-SMA and SLUG and suppressed the invasion abilities of MDA-MA-231 cells. GO and KEGG analyses based on 322 DEGs showed that may be associated with generic transcription in breast cancer.
The study data indicated that BTBD7 was inversely associated with SLUG expression. Higher BTBD7 was associated with poor clinicopathologic features and prognosis in HRNBC patients. silencing inhibited EMT through regulation of SLUG expression. might act as a potential molecular target for gene therapy in HRNBC patients.
激素受体阴性乳腺癌(HRNBC),包括三阴性乳腺癌(TNBC)和人表皮生长因子受体2(HER-2)过表达乳腺癌,易于转移且预后较差。含BTB/POZ结构域蛋白7(Btbd7)被认为可调节SLUG和上皮-间质转化(EMT)过程。然而,Btbd7在HRNBC中的作用尚不清楚。
通过免疫组织化学和免疫荧光对HRNBC肿瘤组织、癌旁正常组织(NAT)以及乳腺癌细胞中BTBD7和SLUG的表达进行表征。用BTBD7 siRNA转染MDA-MA-231细胞,并通过qRT-PCR和蛋白质印迹法进行检测。用蛋白质印迹分析检测Slug和EMT相关蛋白的表达水平。采用细胞侵袭实验分析MDA-MA-231的细胞侵袭能力。用GO和KEGG分析来分析基因功能。
HRNBC肿瘤组织中BTBD7表达的总阳性率为66.7%,高于NAT(52.1%)和乳腺良性病变组织(20%)。在HRNBC组织和MDA-MA-231细胞中可发现SLUG和BTBD7蛋白共表达。沉默BTBD7可显著上调上皮标志物E-钙黏蛋白,下调间质标志物α-平滑肌肌动蛋白和SLUG,并抑制MDA-MA-231细胞的侵袭能力。基于322个差异表达基因的GO和KEGG分析表明,BTBD7可能与乳腺癌的一般转录相关。
研究数据表明,BTBD7与SLUG表达呈负相关。较高的BTBD7与HRNBC患者不良的临床病理特征和预后相关。沉默BTBD7通过调节SLUG表达抑制EMT。BTBD7可能作为HRNBC患者基因治疗的潜在分子靶点。