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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1446920
This article is part of the Research Topic Genomic Discoveries and Pharmaceutical Development in Urologic Tumors View all 16 articles

KHSRP knockdown inhibits papillary renal cell carcinoma progression and sensitizes to gemcitabine

Provisionally accepted
Wei Song Wei Song 1,2Heng Zhang Heng Zhang 3*Yi Lu Yi Lu 1*Houliang Zhang Houliang Zhang 2Jinliang Ni Jinliang Ni 2Lan Chang Lan Chang 4*Yongzhe Gu Yongzhe Gu 2Guangchun Wang Guangchun Wang 2*Tianyuan Xu Tianyuan Xu 2*Zonglin Wu Zonglin Wu 1*Keyi Wang Keyi Wang 1,2*
  • 1 Shanghai Shidong Hospital of Yangpu District, Shanghai, China
  • 2 Shanghai Tenth People's Hospital, Tongji University, Shanghai, Shanghai Municipality, China
  • 3 Guiqian International General Hospital, Guiyang, Guizhou Province, China
  • 4 Shanghai Putuo Mental Health Center, Shanghai, China

The final, formatted version of the article will be published soon.

    Patients diagnosed with papillary renal cell carcinoma (pRCC) exhibit a high rate of clinical metastasis; however, the underlying molecular mechanism is unclear. In this study, KH-type splicing regulatory protein (KHSRP) participated in pRCC progression and was associated with metastasis.It was positively correlated with the hallmark of epithelial-mesenchymal transition. KHSRP inhibition effectively alleviated the cellular function of migration and invasion. Additionally, KHSRP knockdown inhibited the proliferative ability of pRCC cells. A pharmaceutical screening was based on the KHSRP protein structure. Gemcitabine (Gem) decreased KHSRP expression.UIO-66@Gem@si-KHSRP (UGS) nanoparticles (NPs) were prepared for targeted delivery and applied in both in vitro and in vivo experiments to explore the clinical transition of KHSRP. UGS NPs exhibited better performance in inhibiting cellular proliferation, migration, and invasion than Gem. Additionally, the in vivo experiment results confirmed their therapeutic effects in inhibiting tumor metastasis with excellent biosafety. The silico analysis indicated that KHSRP knockdown increased cytotoxic cell infiltration in the tumor microenvironment to potentiate anti-tumor effects.Thus, KHSRP can promote pRCC progression as an oncogene and serve as a target in clinical transition through UGS NP-based therapy.

    Keywords: Papillary renal cell carcinoma, metastasis, KHSRP, gemcitabine, target therapy

    Received: 10 Jun 2024; Accepted: 23 Sep 2024.

    Copyright: © 2024 Song, Zhang, Lu, Zhang, Ni, Chang, Gu, Wang, Xu, Wu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Heng Zhang, Guiqian International General Hospital, Guiyang, 550024, Guizhou Province, China
    Yi Lu, Shanghai Shidong Hospital of Yangpu District, Shanghai, China
    Lan Chang, Shanghai Putuo Mental Health Center, Shanghai, China
    Guangchun Wang, Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200070, Shanghai Municipality, China
    Tianyuan Xu, Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200070, Shanghai Municipality, China
    Zonglin Wu, Shanghai Shidong Hospital of Yangpu District, Shanghai, China
    Keyi Wang, Shanghai Shidong Hospital of Yangpu District, Shanghai, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.