Overexpression of HMGA1 confers radioresistance by transactivating RAD51 in cholangiocarcinoma.
Overexpression of HMGA1 confers radioresistance by transactivating RAD51 in cholangiocarcinoma.
复制标题
HMGA 1过表达通过反式激活胆管癌中的RAD 51赋予放射抗性。
DOI：
10.1038/s41420-021-00721-8
复制
发表时间：
2021-10-29
影响因子：
7
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Song J;Cui D;Wang J;Qin J;Wang S;Wang Z;Zhai X;Ma H;Ma D;Liu Y;Jin B;Liu Z
胆管癌（CCA）是一种罕见但具有侵袭性的胆管肿瘤。 CCA 通常在晚期才被诊断出来，对目前的常规放疗和化疗反应不佳。高迁移率基团 A1 (HMGA1) 是一种结构转录因子，在多种恶性肿瘤中过度表达。在这项研究中，我们发现 HMGA1 的表达在 CCA 中经常升高，并且该基因的高表达与不良预后相关。从功能上讲，HMGA1 促进 CCA 细胞增殖/侵袭和异种移植肿瘤生长。此外，HMGA1 通过两个 HMGA1 响应元件与 RAD51 启动子结合来转录激活 RAD51。值得注意的是，HMGA1 的过度表达会促进放射抗性，而其敲低则会导致 CCA 细胞对 X 射线照射产生放射敏感性。此外，救援实验表明，抑制 RAD51 可逆转 HMGA1 对放射抗性和增殖/侵袭的影响。这些发现表明 HMGA1 作为 RAD51 的新型调节剂发挥作用，并赋予胆管癌放射抗性。
Cholangiocarcinomas (CCAs) are rare but aggressive tumors of the bile ducts. CCAs are often diagnosed at an advanced stage and respond poorly to current conventional radiotherapy and chemotherapy. High mobility group A1 (HMGA1) is an architectural transcription factor that is overexpressed in multiple malignant tumors. In this study, we showed that the expression of HMGA1 is frequently elevated in CCAs and that the high expression of this gene is associated with a poor prognosis. Functionally, HMGA1 promotes CCA cell proliferation/invasion and xenograft tumor growth. Furthermore, HMGA1 transcriptionally activates RAD51 by binding to its promoter through two HMGA1 response elements. Notably, overexpression of HMGA1 promotes radioresistance whereas its knockdown causes radiosensitivity of CCA cells to X-ray irradiation. Moreover, rescue experiments reveal that inhibition of RAD51 reverses the effect of HMGA1 on radioresistance and proliferation/invasion. These findings suggest that HMGA1 functions as a novel regulator of RAD51 and confers radioresistance in cholangiocarcinoma.
登录
查看更多内容
影响因子：
3.7
作者：
Pellarin I;Arnoldo L;Costantini S;Pegoraro S;Ros G;Penzo C;Triolo G;Demarchi F;Sgarra R;Vindigni A;Manfioletti G
通讯作者：
Manfioletti G
影响因子：
4.3
作者：
Hine, Christopher M.;Li, Hongjie;Gorbunova, Vera
通讯作者：
Gorbunova, Vera
影响因子：
11.5
作者：
Chiappetta, G;Botti, G;Fusco, A
通讯作者：
Fusco, A
影响因子：
65.1
作者：
Banales, Jesus M.;Cardinale, Vincenzo;Alvaro, Domenico
通讯作者：
Alvaro, Domenico
影响因子：
3.8
作者：
Alshareeda, Alaa Tarig;Negm, Ola H.;Rakha, Emad A.
通讯作者：
Rakha, Emad A.