Loss of ADAR1 induces ferroptosis of breast cancer cells

作者全名：Yin, Chuan; Zhang, Meng-Meng; Wang, Guo-Liang; Deng, Xiao-Yan; Tu, Zeng; Jiang, Shan-Shan; Gao, Zheng-Dan; Hao, Meng; Chen, Yong; Li, Yi; Yang, Sheng-Yong

作者地址：[Yin, Chuan; Zhang, Meng-Meng; Deng, Xiao-Yan; Jiang, Shan-Shan; Gao, Zheng-Dan; Hao, Meng; Li, Yi; Yang, Sheng-Yong] Chongqing Med Univ, Coll Basic Med, Mol Med & Canc Res Ctr, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China; [Tu, Zeng] Chongqing Med Univ, Coll Basic Med, Dept Pathogen Biol, Chongqing 400016, Peoples R China; [Chen, Yong] Ningxia Med Univ, Gen Hosp, Dept Radiol & Intervent, Yinchuan 750004, Peoples R China; [Wang, Guo-Liang] Huazhong Univ Sci & Technol, Union Hosp, Dept Gen Surg, Wuhan 430022, Peoples R China

通信作者：Li, Y; Yang, SY (通讯作者)，Chongqing Med Univ, Coll Basic Med, Mol Med & Canc Res Ctr, Dept Biochem & Mol Biol, Chongqing 400016, Peoples R China.; Chen, Y (通讯作者)，Ningxia Med Univ, Gen Hosp, Dept Radiol & Intervent, Yinchuan 750004, Peoples R China.

来源：CELLULAR SIGNALLING

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:001254257900001

JCR分区：Q2

影响因子：4.4

年份：2024

卷号：121

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：ADAR1; Ferroptosis; Breast cancer cell; miR-335-5p; GPX4

摘要：Adenosine deaminases acting on RNA 1(ADAR1), an RNA editing enzyme that converts adenosine to inosine by deamination in double-stranded RNAs, plays an important role in occurrence and progression of various types of cancer. Ferroptosis has emerged as a hot topic of cancer research in recent years. We have previously reported that ADAR1 promotes breast cancer progression by regulating miR-335-5p and METTL3. However, whether ADAR1 has effects on ferroptosis in breast cancer cells is largely unknown. In this study, we knocked down ADAR1 using CRISPR-Cas9 technology or over-expressed ADAR1 protein using plasmid expressing ADAR1 in MCF-7 and MDA-MB-231 breast cancer cell lines, then detected cell viability, and levels of ROS, MDA, GSH, Fe2+, GPX4 protein and miR-335-5p. We showed that the cell proliferation was inhibited, levels of ROS, MDA, Fe2+, and miR-335-5p were increased, while GSH and GPX4 levels were decreased after loss of ADAR1, compared to the control group. The opposite effects were observed after ADAR1 overexpression in the cells. Further, we demonstrated that ADAR1-controlled miR-335-5p targeted Sp1 transcription factor of GPX4, a known ferroptosis molecular marker, leading to inhibition of ferroptosis by ADAR1 in breast cancer cells. Moreover, RNA editing activity of ADAR1 is not essential for inducing ferroptosis. Collectively, loss of ADAR1 induces ferroptosis in breast cancer cells by regulating miR-335-5p/Sp1/GPX4 pathway. The findings may provide insights into the mechanism by which ADAR1 promotes breast cancer progression via inhibiting ferroptosis.

基金机构：National Natural Science Foundation of China [81872444, 81602159]; Natural Science Foundation of Chongqing Grants [cstc2021jcyj-msxmX0238, cstc2016jcyjA0054]; Science and Technology Planning Project of Yuzhong District, Chongqing City [20170109]

基金资助正文：This research was supported by the National Natural Science Foundation of China Grants 81872444 (S.-Y.Y.) , 81602159 (Y.L.) , the Natural Science Foundation of Chongqing Grants cstc2021jcyj-msxmX0238 (S.-Y.Y.) , cstc2016jcyjA0054 (Y.L.) , and the Science and Technology Planning Project of Yuzhong District, Chongqing City Grant 20170109 (S.-Y. Y.) .