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Paclitaxel-induced stress granules increase LINE-1 mRNA stability to promote drug resistance in breast cancer cells |
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| Authors: | Xiao Shi Xinxin Si Ershao Zhang Ruochen Zang Nan Yang He Cheng Zhihong Zhang Beijing Pan Yujie Sun |
| Affiliation: | 1.Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu 211166, China2.Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu 211166, China3.Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China4.Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210036, China |
| Abstract: | 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. |
| Keywords: | LINE-1 stress granules RNA stability neoplasm drug resistance triple negative breast cancer |
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