Docetaxel resistance-derived LINC01085 contributes to the immunotherapy of hormone-independent prostate cancer by activating the STING/MAVS signaling pathway

Jiwei Zhang; Shengli Li; Jianian Zhang; Wen Zhang; Jiawen Jiang; Hao Wu; Enjiang Wu; Yutao Feng; Li Yang; Zhe Li

doi:10.1016/j.canlet.2022.215829

Docetaxel resistance-derived LINC01085 contributes to the immunotherapy of hormone-independent prostate cancer by activating the STING/MAVS signaling pathway

Cancer Lett. 2022 Oct 1:545:215829. doi: 10.1016/j.canlet.2022.215829. Epub 2022 Jul 19.

Authors

Jiwei Zhang¹, Shengli Li², Jianian Zhang³, Wen Zhang⁴, Jiawen Jiang⁴, Hao Wu⁴, Enjiang Wu⁵, Yutao Feng⁵, Li Yang⁶, Zhe Li⁷

Affiliations

¹ Shanghai Key Laboratory of Compound Chinese Medicines, The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: joezhang@shutcm.edu.cn.
² Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, 201620, China.
³ Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai, 200072, China.
⁴ School of Life Sciences, Shanghai University, Shanghai, 200444, China.
⁵ Shanghai Key Laboratory of Compound Chinese Medicines, The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
⁶ Shanghai Key Laboratory of Compound Chinese Medicines, The MOE Key Laboratory for Standardization of Chinese Medicines and the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: yl7@shutcm.edu.cn.
⁷ School of Life Sciences, Shanghai University, Shanghai, 200444, China. Electronic address: zhe_li0913@shu.edu.cn.

PMID: 35868534
DOI: 10.1016/j.canlet.2022.215829

Abstract

Acquired docetaxel (doc) resistance, one of the major reasons for unfavorable prognosis in patients with aggressive hormone-independent prostate cancer (HIPC), is a major obstacle for patient treatment. Dysregulation of long non-coding RNAs promotes or suppresses chemoresistance in multiple cancers; however, the specific molecular mechanisms underlying HIPC remain unknown. In this study, we found that the LINC01085, as a tumor-suppressor, which showed significant clinically relevant in HIPC patients with doc-resistance. Mechanistically, in docetaxel-sensitive cells, LINC01085 could specifically bind to both TANK-binding kinase 1 (TBK1) and glycogen synthase kinase 3β (GSK3β), and higher LINC01085 RNA levels could inhibit TBK1 dimerization. Whereas, in doc-resistant cells, lower LINC01085 RNA level lost the strong binding with both, meanwhile, the interaction between TBK1 and GSK3β enhanced which accelerated TBK1 phosphorylation at the Ser-172 site, resulting in decreased expression levels of PD-L1 and NF-κB as well as the secretion of type I/III interferons. Thus, Overexpression of LINC01085 combined with immune checkpoint blockade is an effective strategy for the treatment of HIPC patients.

Keywords: Docetaxel resistance; Long non-coding RNA; Prostate cancer; TANK binding Kinase 1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Docetaxel / pharmacology
Glycogen Synthase Kinase 3 beta
Hormones
Humans
Immunotherapy
Interferon Type I*
Male
Prostatic Neoplasms* / drug therapy
Prostatic Neoplasms* / genetics
RNA
Signal Transduction

Substances

Hormones
Interferon Type I
Docetaxel
RNA
Glycogen Synthase Kinase 3 beta