• ISSN 1674-8301
  • CN 32-1810/R
Volume 35 Issue 6
Nov.  2021
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Article Contents
Xiao Shi, Xinxin Si, Ershao Zhang, Ruochen Zang, Nan Yang, He Cheng, Zhihong Zhang, Beijing Pan, Yujie Sun. Paclitaxel-induced stress granules increase LINE-1 mRNA stability to promote drug resistance in breast cancer cells[J]. The Journal of Biomedical Research, 2021, 35(6): 411-424. doi: 10.7555/JBR.35.20210105
Citation: Xiao Shi, Xinxin Si, Ershao Zhang, Ruochen Zang, Nan Yang, He Cheng, Zhihong Zhang, Beijing Pan, Yujie Sun. Paclitaxel-induced stress granules increase LINE-1 mRNA stability to promote drug resistance in breast cancer cells[J]. The Journal of Biomedical Research, 2021, 35(6): 411-424. doi: 10.7555/JBR.35.20210105

Paclitaxel-induced stress granules increase LINE-1 mRNA stability to promote drug resistance in breast cancer cells

doi: 10.7555/JBR.35.20210105
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  • Corresponding author: Yujie Sun, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University; and Department of Cell Biology, School of Basic Medical Sciences, Nanjing Medical University, 101 Longmian Avenue, Jiangning District, Nanjing Jiangsu 211166, China. Tel: +86-25-86869428, E-mail: yujiesun@njmu.edu.cn
  • Received: 2021-06-30
  • Revised: 2021-08-20
  • Accepted: 2021-08-24
  • Published: 2021-10-30
  • Issue Date: 2021-11-27
  • 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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