LINC00589-dominated ceRNA networks regulate multiple chemoresistance and cancer stem cell-like properties in HER2+ breast cancer

Resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapy (trastuzumab), cancer stem cell (CSC)-like properties and multiple chemoresistance often concur and intersect in breast cancer, but molecular links that may serve as effective therapeutic targets remain largely unknown. H...

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Bibliographic Details
Published in:NPJ breast cancer 2022-10, Vol.8 (1), p.115-115, Article 115
Main Authors: Bai, Wendong, Peng, Hongyan, Zhang, Jiarui, Zhao, Yongmei, Li, Zhijun, Feng, Xuelian, Zhang, Jiang, Liang, Fei, Wang, Li, Zhang, Nan, Li, Yize, Zhu, Huayu, Ji, Qiuhe
Format: Article
Language:English
Subjects:
631/337/384
692/4028/67/1059/2326
692/53/2422
692/699/67/1347
Biomedical and Life Sciences
Biomedicine
Biopsy
Breast cancer
Cancer Research
Cell Biology
Cloning
Drug resistance
Epidermal growth factor
Human Genetics
Liver cancer
Lymphatic system
Medical prognosis
Medical research
Oncology
Patients
Proteins
Roles
Stem cells
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Summary:Resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapy (trastuzumab), cancer stem cell (CSC)-like properties and multiple chemoresistance often concur and intersect in breast cancer, but molecular links that may serve as effective therapeutic targets remain largely unknown. Here, we identified the long noncoding RNA, LINC00589 as a key regulatory node for concurrent intervention of these processes in breast cancer cells in vitro and in vivo. We demonstrated that the expression of LINC00589 is clinically valuable as an independent prognostic factor for discriminating trastuzumab responders. Mechanistically, LINC00589 serves as a ceRNA platform that simultaneously sponges miR-100 and miR-452 and relieves their repression of tumor suppressors, including discs large homolog 5 ( DLG5 ) and PR/SET domain 16 ( PRDM16 , a transcription suppressor of mucin4 ), thereby exerting multiple cancer inhibitory functions and counteracting drug resistance. Collectively, our results disclose two LINC00589 -initiated ceRNA networks, the LINC00589 - miR-100 - DLG5 and LINC00589 - miR-452 - PRDM16 - mucin4 axes, which regulate trastuzumab resistance, CSC-like properties and multiple chemoresistance of breast cancer, thus providing potential diagnostic and prognostic markers and therapeutic targets for HER2-positive breast cancer.
ISSN:2374-4677
2374-4677
DOI:10.1038/s41523-022-00484-0