Xu Jia, Liu Xiaoyuan, Huang Zebo, Lu Tingxun, Zhang Ying, Cai Dongyan, Li Xia
Department of Pharmacy, Affiliated Hospital of Jiangnan University, Wuxi, 214000, Jiangsu, China.
Department of Oncology, Affiliated Hospital of Jiangnan University, Wuxi, 214000, Jiangsu, China.
Biochem Genet. 2024 Jul 24. doi: 10.1007/s10528-024-10885-4.
Esophageal cancer (EC), a prevalent malignancy, has a high incidence and mortality. X-ray repair cross complementing 2 (XRCC2) functions on DNA damage and repair that works the progression of various cancers. Nevertheless, the role and mechanism of XRCC2 remain unknown in EC. The XRCC2 expression was examined by reverse transcription quantitative polymerase chain reaction and western blot. The function of XRCC2 in EC were investigated through cell counting kit-8, colony formation, transwell, flow cytometry, chromatin immunoprecipitation, luciferase, and western blot experiments. Besides, the role of XRCC2 in EC was assessed by western blot and immunohistochemistry experiments after nude mice were injected with EC109 cells and treated with nab-paclitaxel. The XRCC2 expression was upregulated in EC. Knockdown of XRCC2 diminished cell viability, and the number of colonies, migration cells and invasion cells of KYSE150 and EC109 cells. Silencing of XRCC2 diminished the cell viability of both two cells with a lower IC50, whereas boosted the apoptosis rate of both cells with the treatment of albumin-paclitaxel. All these outcomes were reverse with the upregulation of XRCC2 in both two cells. Mechanically, XRCC2 was transcriptionally regulated by specificity protein 1 (SP1), and silencing of SP1 inhibited the cell growth of EC. In vivo, transfection of shXRCC2 with or without albumin-paclitaxel treatment both decreased the tumor size and weight, as well as the expression of XRCC2 and Ki-67 in xenografted mice. XRCC2 transcriptionally regulated by SP2 promoted proliferation, migration, invasion, and chemoresistance of EC cells.
食管癌（EC）是一种常见的恶性肿瘤，发病率和死亡率都很高。X射线修复交叉互补蛋白2（XRCC2）在DNA损伤和修复中发挥作用，这与多种癌症的进展有关。然而，XRCC2在食管癌中的作用和机制尚不清楚。通过逆转录定量聚合酶链反应和蛋白质免疫印迹法检测XRCC2的表达。通过细胞计数试剂盒-8、集落形成、Transwell、流式细胞术、染色质免疫沉淀、荧光素酶和蛋白质免疫印迹实验研究XRCC2在食管癌中的功能。此外，在裸鼠注射EC109细胞并用纳米白蛋白结合型紫杉醇处理后，通过蛋白质免疫印迹和免疫组织化学实验评估XRCC2在食管癌中的作用。XRCC2在食管癌中表达上调。敲低XRCC2可降低KYSE150和EC109细胞的活力、集落数量、迁移细胞和侵袭细胞数量。沉默XRCC2可降低两种细胞的活力，且半数抑制浓度（IC50）更低，而用白蛋白结合型紫杉醇处理则可提高两种细胞的凋亡率。在两种细胞中上调XRCC2后，所有这些结果都发生了逆转。机制上，XRCC2受特异性蛋白1（SP1）转录调控，沉默SP1可抑制食管癌的细胞生长。在体内，转染shXRCC2无论是否联合白蛋白结合型紫杉醇处理，均可减小异种移植小鼠的肿瘤大小和重量，以及降低XRCC2和Ki-67的表达。受SP2转录调控的XRCC2促进了食管癌细胞的增殖、迁移、侵袭和化疗耐药性。
