Pan Ruijun, Yu Dingye, Hu Jiajia, Yang Xiao, Wang Chenxing, Zhang Luyang, Xue Pei, Sun Jing, Zhang Xiaoping, Cai Wei
Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Minimally Invasive Surgery Center, Shanghai, China.
Cell Death Discov. 2022 May 16;8(1):263. doi: 10.1038/s41420-022-01057-7.
In colorectal cancer (CRC), the development of reagents that increase sensitivity to chemotherapeutic agents could prevent drug resistance and improve patient survival. Scm-like with four malignant brain tumor domains 1 (SFMBT1) is up-regulated in CRC tumor tissues and cells and may be associated with drug resistance. We detected the expression of SFMBT1 in CRC tissue microarrays by immunohistochemistry. The role of SFMBT1 in the migration, proliferation and invasion of CRC or resistance to 5-fluorouracil (5-FU) was determined using scratch assay, colony formation and Transwell assay. Fluorescence co-localization and immunoprecipitation were used to analyze the correlation between SFMBT1 and high mobility group domain-containing protein 20 A (HMG20A). Xenograft experiments were conducted to investigate the role of SFMBT1 and HMG20A in tumor growth and metastasis in vivo. We found that SFMBT1 is up-regulated in CRC and its expression is further amplified in 5-FU resistance. SFMBT1 drives 5-FU resistance and CRC proliferation, migration and invasion. Correlation analysis shows that SFMBT1 and HMG20A are positively correlated. Mechanistically, fluorescence co-localization and immunoprecipitation assay indicate an interaction between SFMBT1 and HMG20A. Depletion of SFMBT1 down-regulates HMG20A downstream. These results were verified by murine xenograft and lung metastasis models. Our results indicate that the SFMBT1/HMG20A axis could be targeted to increase the resistance of CRC cells to 5-FU.
在结直肠癌（CRC）中，开发能够提高对化疗药物敏感性的试剂可以预防耐药性并提高患者生存率。含四个恶性脑肿瘤结构域的类Scm蛋白1（SFMBT1）在CRC肿瘤组织和细胞中上调，可能与耐药性有关。我们通过免疫组织化学检测了CRC组织芯片中SFMBT1的表达。使用划痕试验、集落形成试验和Transwell试验确定了SFMBT1在CRC迁移、增殖、侵袭或对5-氟尿嘧啶（5-FU）耐药中的作用。采用荧光共定位和免疫沉淀法分析SFMBT1与含高迁移率族结构域蛋白20A（HMG20A）之间的相关性。进行异种移植实验以研究SFMBT1和HMG20A在体内肿瘤生长和转移中的作用。我们发现SFMBT1在CRC中上调，其表达在5-FU耐药中进一步增强。SFMBT1导致5-FU耐药以及CRC的增殖、迁移和侵袭。相关性分析表明SFMBT1与HMG20A呈正相关。机制上，荧光共定位和免疫沉淀试验表明SFMBT1与HMG20A之间存在相互作用。敲低SFMBT1会下调下游的HMG20A。这些结果在小鼠异种移植和肺转移模型中得到了验证。我们的结果表明，靶向SFMBT1/HMG20A轴可以增加CRC细胞对5-FU的耐药性。
