piRNA-823 Is Involved in Cancer Stem Cell Regulation Through Altering DNA Methylation in Association With Luminal Breast Cancer

Frontiers in Cell and Developmental Biology

Jinhui Lü¹  Richard G. Pestell²  Chunli Liang³  Zuoren Yu³  Ya Li³  Qian Zhao³  Pengfei Liu³  Xin Ding³  Wenjing Ma³  Yuefan Guo³  Ziye Lu⁴ 

[1] Dalian Medical University, Dalian, China;Pennsylvania Cancer and Regenerative Medicine Research Center, Baruch S. Blumberg Institute, Doylestown, PA, United States;Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China;University College London, London, United Kingdom;

关键词: piR-823;    cancer stem cell;    breast cancer;    DNA methylation;    non-coding RNAs;   

DOI  :  10.3389/fcell.2021.641052

来源: DOAJ

【 摘 要 】

Cancer stem cells (CSCs) are believed to be the main source of cancer relapse and metastasis. PIWI-interacting small non-coding RNAs (piRNAs) have been recently recognized to be relevant to cancer biology. Whether and how piRNAs regulate human CSCs remain unknown. Herein, upregulation of piR-823 was identified in tested luminal breast cancer cells, especially in the luminal subtype of breast CSCs. Enforced expression or targeted knockdown of piR-823 demonstrated its oncogenic function in regulating cell proliferation and colony formation in MCF-7 and T-47D breast cancer cells. In addition, piR-823 induced ALDH (+) breast CSC subpopulation promoted the expression of stem cell markers including OCT4, SOX2, KLF4, NANOG, and hTERT, and increased mammosphere formation. Tail vein injection of magnetic nanoparticles carrying anti-piR-823 into the mammary gland of tumor-burdened mice significantly inhibited tumor growth in vivo. DNA methyltransferases (DNMTs) including DNMT1, DNMT3A, and DNMT3B were demonstrated to be the downstream genes of piR-823, which regulate gene expression by maintaining DNA methylation. piR-823 increased the expression of DNMTs, promoted DNA methylation of gene adenomatous polyposis coli (APC), thereby activating Wnt signaling and inducing cancer cell stemness in the luminal subtype of breast cancer cells. The current study not only revealed a novel mechanism through which piRNAs contribute to tumorigenesis in breast cancer by regulating CSCs, but also provided a therapeutic strategy using non-coding genomes in the suppression of human breast cancer.

【 授权许可】

Unknown