2. Academic Validation
  3. PiRNA-4447944 promotes castration-resistant growth and metastasis of prostate cancer by inhibiting NEFH expression through forming the piRNA-4447944-PIWIL2-NEFH complex

PiRNA-4447944 promotes castration-resistant growth and metastasis of prostate cancer by inhibiting NEFH expression through forming the piRNA-4447944-PIWIL2-NEFH complex

  • Int J Biol Sci. 2024 Jul 1;20(9):3638-3655. doi: 10.7150/ijbs.96173.
Qiang Peng 1,  Yu Chen 2 3 4,  Tingting Xie 1,  Dandan Pu 5,  Vincy Wing-Sze Ho 1,  Jingkai Sun 1,  Kang Liu 1,  Ronald Cheong-Kin Chan 6,  Xiaofan Ding 7,  Jeremy Yuen-Chun Teoh 1,  Xin Wang 8,  Peter Ka-Fung Chiu 1,  Chi-Fai Ng 1
Affiliations

Affiliations

  • 1 SH Ho Urology Centre, Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China.
  • 2 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan, China.
  • 3 Department of Biomedical Sciences and Tung Biomedical Sciences Centre, City University of Hong Kong, Hong Kong, China.
  • 4 HitGen Inc., Building 6, No.8 Huigu First East Road, Tianfu International Bio-Town, Shuangliu District, Chengdu, Sichuan, China.
  • 5 Department of Surgery, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong, Hong Kong, China.
  • 6 Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China.
  • 7 Faculty of Health Sciences, University of Macau, Macau, China.
  • 8 Department of Surgery, The Chinese University of Hong Kong, Hong Kong, China.
PMID: 38993562 DOI: 10.7150/ijbs.96173
Abstract

Castration-resistant prostate Cancer (CRPC) is the leading cause of prostate Cancer (PCa)-related death in males, which occurs after the failure of androgen deprivation therapy (ADT). PIWI-interacting RNAs (piRNAs) are crucial regulators in many human cancers, but their expression patterns and roles in CRPC remain unknown. In this study, we performed small RNA Sequencing to explore CRPC-associated piRNAs using 10 benign prostate tissues, and 9 paired hormone-sensitive PCa (HSPCa) and CRPC tissues from the same patients. PiRNA-4447944 (piR-4447944) was discovered to be highly expressed in CRPC group compared with HSPCa and benign groups. Functional analyses revealed that piR-4447944 overexpression endowed PCa cells with castration resistance ability in vitro and in vivo, whereas knockdown of piR-4447944 using anti-sense RNA suppressed the proliferation, migration and invasion of CRPC cells. Additionally, enforced piR-4447944 expression promoted in vitro migration and invasion of PCa cells, and reduced cell Apoptosis. Mechanistically, piR-4447944 bound to PIWIL2 to form a piR-4447944/PIWIL2 complex and inhibited tumor suppressor NEFH through direct interaction at the post-transcriptional level. Collectively, our study indicates that piR-4447944 is essential for prostate tumor-propagating cells and mediates androgen-independent growth of PCa, which extends current understanding of piRNAs in Cancer biology and provides a potential approach for CRPC treatment.

Keywords

NEFH; PIWI-interacting RNAs; castration resistance; piR-4447944; prostate cancer.

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