Identification of BRMS1L as Metastasis Suppressing Gene in Esophageal Squamous Cell Carcinoma
Identification of BRMS1L as Metastasis Suppressing Gene in Esophageal Squamous Cell Carcinoma
复制标题
BRMS1L作为食管鳞状细胞癌转移抑制基因的鉴定
DOI：
10.2147/cmar.s232632
复制
发表时间：
2020
影响因子：
3.3
通讯作者：
Lv Xiao-Bin
中科院分区：
文献类型：
--
作者：
Zhou Ruihao;Tang Xiaofeng;Li Liping;Zhang Feifei;Sun Jun;Ju Cheng;Zhou Yan;Liu Renfeng;Liang Yiping;Lv Bin;Zhang Zhiping;Hu Haiyan;Lv Xiao-Bin
乳腺癌转移抑制因子1样（BRMS 1-like）是第一个被报道为Sin 3-HDAC复合物的组成部分，但在癌症进展中的作用在很大程度上是未知的。我们的前期研究报道BRMS 1 L通过促进HDAC复合物募集到FZD 10启动子上，从而抑制FZD 10的转录，从而促进乳腺癌的转移。方法检测BRMS 1 L在食管鳞癌组织中的表达水平。通过transwell试验、伤口愈合试验和细胞粘附试验探索了BRMS 1 L在TE-1D（敲除）和ECA-109（过表达）细胞系中的作用。采用定量真实的-time PCR、Western blot分析和荧光素酶测定来检测CBP/P300-BRMS 1 L-ITGA 7轴的相互作用。结果在本研究中，我们发现BRMS 1 L基因的敲低促进了细胞的迁移、侵袭和上皮-间质转化（EMT）。相反，BRMS 1 L过表达抑制ESCC的迁移和侵袭。BRMS 1 L通过转录抑制ITGA 7表达发挥其转移抑制作用。CBP/p300基因可调控BRMS 1 L的表达，可能是下调BRMS 1 L表达的重要机制。结论CBP/p300-BRMS 1 L-ITGA 7轴在食管鳞癌转移中的作用可能与其在食管癌转移中的作用有关。
Introduction Breast cancer metastasis suppressor 1 like (BRMS1-like)was first reported to be a component of the Sin3-HDAC complex, but the role in the progression of cancers was largely unknown. Our previous study reported that BRMS1L promoted the metastasis of breast cancer through facilitating the recruitment of HDAC complex to the promoter FZD10, and hence suppressing the transcription of FZD10. Methods In this study, we detected the expression level of BRMS1L in esophageal squamous cell carcinoma (ESCC). The effect of BRMS1L in TE-1D (knockdown) and ECA-109 (overexpression) cell lines was explored by transwell assays, wound healing assays, and cell adhesion assays. Quantitative real‑time PCR, Western blot analysis, and luciferase assays were used to detect the interaction of the CBP/P300-BRMS1L-ITGA7 axis. Results In the present study, we found that knockdown of BRMS1L promoted the migration, invasion, and epithelial–mesenchymal transition (EMT). Conversely, overexpression of BRMS1L inhibited the migration and invasion of ESCC. Mechanistically, BRMS1L exerted their metastasis-suppressing role via transcriptionally repress ITGA7 expression. Moreover, we revealed that CBP/p 300 regulated the expression of BRMS1L and might be responsible for the down-regulation of BRMS1L in ESCC. Conclusion Collectively, we identified the role of CBP/p300-BRMS1L-ITGA7 axis in the metastasis of ESCC.