2. Academic Validation
  3. piRNA-1742 promotes renal cell carcinoma malignancy by regulating USP8 stability through binding to hnRNPU and thereby inhibiting MUC12 ubiquitination

piRNA-1742 promotes renal cell carcinoma malignancy by regulating USP8 stability through binding to hnRNPU and thereby inhibiting MUC12 ubiquitination

  • Exp Mol Med. 2023 Jun 19. doi: 10.1038/s12276-023-01010-3.
Wentao Zhang # 1 2,  Zongtai Zheng # 3,  Keyi Wang # 1 2,  Weipu Mao # 1 2 4,  Xue Li 5,  Guangchun Wang 1 2,  Yuanyuan Zhang 6,  Jianhua Huang 1 2,  Ning Zhang 7,  Pengfei Wu 1 2,  Ji Liu 1 2,  Haimin Zhang 1 2,  Jianping Che 1 2,  Bo Peng 8 9,  Junhua Zheng 10 11,  Wei Li 12 13 14,  Xudong Yao 15 16
Affiliations

Affiliations

  • 1 Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, P. R. China.
  • 2 Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, P. R. China.
  • 3 Department of Urology, Guangdong Second Provincial General Hospital, Guangzhou, P. R. China.
  • 4 Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, P. R. China.
  • 5 Department of Pathology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, P. R. China.
  • 6 Institute for Regenerative Medicine, Wake Forest University, Winston-Salem, NC, USA.
  • 7 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
  • 8 Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, P. R. China. pengbo6908@163.com.
  • 9 Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, P. R. China. pengbo6908@163.com.
  • 10 State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University, Shanghai, P. R. China. zhengjh0471@sina.com.
  • 11 Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P. R. China. zhengjh0471@sina.com.
  • 12 Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, P. R. China. weili06@tongji.edu.cn.
  • 13 Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, P. R. China. weili06@tongji.edu.cn.
  • 14 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. weili06@tongji.edu.cn.
  • 15 Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, P. R. China. yaoxudong1967@163.com.
  • 16 Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, P. R. China. yaoxudong1967@163.com.
  • # Contributed equally.
PMID: 37332045 DOI: 10.1038/s12276-023-01010-3
Abstract

Accumulating studies have confirmed that PIWI-interacting RNAs (piRNAs) are considered epigenetic effectors in Cancer. We performed piRNA microarray expression analysis on renal cell carcinoma (RCC) tumor tissues and paired normal tissues and performed a series of in vivo and in vitro experiments to explore piRNAs associated with RCC progression and investigate their functional mechanisms. We found that piR-1742 was highly expressed in RCC tumors and that patients with high piR-1742 expression had a poor prognosis. Inhibition of piR-1742 significantly reduced tumor growth in RCC xenograft and Organoid models. Mechanistically, piRNA-1742 regulates the stability of USP8 mRNA by binding directly to hnRNPU, which acts as a deubiquitinating Enzyme that inhibits the ubiquitination of MUC12 and promotes the development of malignant RCC. Subsequently, nanotherapeutic systems loaded with piRNA-1742 inhibitors were found to effectively inhibit the metastasis and growth of RCC in vivo. Therefore, this study highlights the functional importance of piRNA-related ubiquitination in RCC and demonstrates the development of a related nanotherapeutic system, possibly contributing to the development of therapeutic approaches for RCC.

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