ACTL6A deficiency induces apoptosis through impairing DNA replication and inhibiting the ATR-Chk1 signaling in glioblastoma cells

作者全名："Hu, Xiaosong; Pei, Dakun; Ci, Mingxin; Zhang, Guanghui; Li, Benqin; Wang, Jie; Shen, Yue; Zhai, Xuan; Liang, Ping; Cui, Hongjuan"

作者地址："[Hu, Xiaosong; Pei, Dakun; Ci, Mingxin; Zhang, Guanghui; Cui, Hongjuan] Southwest Univ, State Key Lab Silkworm Genome Biol, 2 Tiansheng St, Chongqing 400716, Peoples R China; [Li, Benqin; Wang, Jie; Shen, Yue; Cui, Hongjuan] Southwest Univ, Ctr Canc, Med Res Inst, Chongqing 400716, Peoples R China; [Zhai, Xuan; Liang, Ping] Chongqing Med Univ, Childrens Hosp, Dept Neurosurg, 136 Zhongshan 2nd Rd, Chongqing 400014, Peoples R China; [Zhai, Xuan; Liang, Ping] Chongqing Key Lab Pediat, Chongqing 400010, Peoples R China"

通信作者："Cui, HJ (通讯作者)，Southwest Univ, State Key Lab Silkworm Genome Biol, 2 Tiansheng St, Chongqing 400716, Peoples R China.; Liang, P (通讯作者)，Chongqing Med Univ, Childrens Hosp, Dept Neurosurg, 136 Zhongshan 2nd Rd, Chongqing 400014, Peoples R China."

来源：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000759467800009

JCR分区：Q2

影响因子：3.1

年份：2022

卷号：599

期号：　

开始页：148

结束页：155

文献类型：Article

关键词：ACTL6A; DNA replication; MCM5; ATR-Chk1 pathway; Glioblastoma

摘要："Actin-like 6A (ACTL6A) is a core subunit of the SWI/SNF chromatin remodeling complex and is highly expressed in several types of human cancers including glioblastoma. Recent studies verified that ACTL6A regulates the proliferation, differentiation, and migration of cancer cells. In this study, we identified ACTL6A as an important regulator of DNA replication. ACTL6A knockdown could impair the DNA replication initiation in glioblastoma cells. The regulation of DNA replication by ACTL6A was mediated through regulating the expression of the CDC45-MCM-GINS (CMG) complex genes. Further investigation revealed that ACTL6A transcriptionally regulates MCM5 expression. Furthermore, ACTL6A knockdown induced DNA damage and diminished the activity of the ATR-Chk1 pathway, which ultimately led glioblastoma cells to apoptosis and death. Taken together, our findings highlight the critical role of ACTL6A in DNA replication and ATR-Chk1 pathway, and reveal a potential target for therapeutic intervention in glioblastoma. (c) 2022 Elsevier Inc. All rights reserved."

基金机构：National Natural Science Foundation of China [81872071]; Natural Science Foundation of Chongqing [cstc2019jcyj-zdxmX0 033]; Fundamental Research Funds for the Central Universities [XYDS201912]

基金资助正文："This research was supported by the the National Natural Science Foundation of China (81872071) , the Natural Science Foundation of Chongqing (cstc2019jcyj-zdxmX0 033) , the Fundamental Research Funds for the Central Universities (XYDS201912) ."