Zhou Shuliang, Xiao Youde, Zhuang Yafei, Liu Yinyin, Zhao Hong, Yang Hui, Xie Conghua, Zhou Fuxiang, Zhou Yunfeng
Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
Oncol Rep. 2017 Jul;38(1):515-521. doi: 10.3892/or.2017.5707. Epub 2017 Jun 6.
Homeobox containing 1 (HMBOX1) modulates telomere length in various types of tumor cells by binding to double‑stranded telomeric DNA. There is a negative correlation between telomere length and radiosensitivity in tumor cells. In the present study, we aimed to investigate the relationship among HMBOX1, telomere and radiosensitivity in cervical cancer cells. Lentivirus-based shRNAs were used to establish stable transfected cell lines in which protein and mRNA levels of HMBOX1 were notably decreased. Knockdown of HMBOX1 increased the radiosensitivity of HeLa and C33A cells. TERT protein was also decreased while HMBOX1 was downregulated. Knockdown of HMBOX1 shortened telomere length in the HeLa cells, while TERT overexpression rescued telomere shortening in the HeLa-HMBOX1 cells. Knockdown of HMBOX1 increased the apoptosis rate, decreased radiation-induced DNA damage foci, and inhibited the expression of ATM, ATR, p-ATM, p-ATR and BRCA1 in the homologous recombination repair pathway. Our data suggest a possible role of HMBOX1 in regulating radiosensitivity in cervical cancer cells. Moreover, HMBOX1 may be a potential factor in the radiotherapy of cervical cancer.
含同源框1（HMBOX1）通过与双链端粒DNA结合来调节多种肿瘤细胞中的端粒长度。肿瘤细胞中端粒长度与放射敏感性呈负相关。在本研究中，我们旨在探究宫颈癌细胞中HMBOX1、端粒与放射敏感性之间的关系。基于慢病毒的短发夹RNA（shRNAs）被用于建立稳定转染细胞系，其中HMBOX1的蛋白质和mRNA水平显著降低。敲低HMBOX1可增加HeLa和C33A细胞的放射敏感性。当HMBOX1下调时，端粒酶逆转录酶（TERT）蛋白也减少。敲低HMBOX1可缩短HeLa细胞中的端粒长度，而TERT过表达可挽救HeLa-HMBOX1细胞中的端粒缩短。敲低HMBOX1可增加凋亡率，减少辐射诱导的DNA损伤灶，并抑制同源重组修复途径中ATM、ATR、磷酸化ATM（p-ATM）、磷酸化ATR（p-ATR）和乳腺癌1号基因（BRCA1）的表达。我们的数据表明HMBOX1在调节宫颈癌细胞放射敏感性中可能发挥作用。此外，HMBOX1可能是宫颈癌放射治疗中的一个潜在因素。
