Paclitaxel-induced stress granules increase LINE-1 mRNA stability to promote drug resistance in breast cancer cells
Xiao Shi1
Xinxin Si1
Ershao Zhang1
Ruochen Zang1
Nan Yang1
He Cheng2
Zhihong Zhang3
Beijing Pan3
Yujie Sun4
1.Key Laboratory of Human Functional Genomics of Jiangsu Province,Nanjing Medical University,Nanjing,Jiangsu 211166,China2.Key Laboratory of Human Functional Genomics of Jiangsu Province,Nanjing Medical University,Nanjing,Jiangsu 211166,China;Department of Cell Biology,School of Basic Medical Sciences,Nanjing Medical University,Nanjing,Jiangsu 211166,China3.Department of Pathology,the First Affiliated Hospital of Nanjing Medical University,Nanjing,Jiangsu 210036,China4.Key Laboratory of Human Functional Genomics of Jiangsu Province,Nanjing Medical University,Nanjing,Jiangsu 211166,China;Department of Cell Biology,School of Basic Medical Sciences,Nanjing Medical University,Nanjing,Jiangsu 211166,China;Collaborative Innovation Center for Cancer Personalized Medicine,Nanjing Medical University,Nanjing,Jiangsu 211166,China
摘要：Abnormal expression of long interspersed element-1 (LINE-1) has been implicated in drug resistance,while our previous study showed that chemotherapy drug paclitaxel (PTX) increased LINE-1 level with unknown mechanism.Bioinformatics analysis suggested the regulation of LINE-1 mRNA by drug-induced stress granules(SGs).This study aimed to explore whether and how SGs are involved in drug-induced LINE-1 increase and thereby promotes drug resistance of triple negative breast cancer (TNBC) cells.We demonstrated that SGs increased LINE-1 expression by recruiting and stabilizing LINE-1 mRNA under drug stress,thereby adapting TNBC cells to chemotherapy drugs.Moreover,LINE-1 inhibitor efavirenz (EFV) could inhibit drug-induced SG to destabilize LINE-1.Our study provides the first evidence of the regulation of LINE-1 by SGs that could be an important survival mechanism for cancer cells exposed to chemotherapy drugs.The findings provide a useful clue for developing new chemotherapeutic strategies against TNBCs.
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分类号：R737.9(泌尿生殖器肿瘤)
论文发表日期：2021-11-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：14( 411-424 )
英文信息