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USPs and non-coding RNAs: Unraveling their interplay within tumor microenvironment for targeted cancer therapy

Yongqing Xu1, Jin Wang2, Xin Deng3

  • 1Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110004, China.

Pharmacological Research
|July 10, 2025
PubMed

Insights

Deubiquitinating enzymes (DUBs) and non-coding RNAs (ncRNAs) interact to influence cancer progression and treatment resistance. Targeting this USP-ncRNA axis, especially with nanodelivery, offers new therapeutic strategies for cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cancer is a major global health challenge characterized by cellular dysregulation and a complex tumor microenvironment (TME).
  • Ubiquitination and deubiquitination, regulated by deubiquitinating enzymes (DUBs), are critical post-transcriptional modifications impacting cellular processes.
  • The interplay of DUBs, particularly ubiquitin-specific proteases (USPs), and non-coding RNAs (ncRNAs) significantly influences cancer development and heterogeneity.

Purpose of the Study:

  • To review the complex interactions between USPs and ncRNAs in cancer.
  • To explore how these interactions affect key cancer hallmarks and the TME.
  • To highlight the therapeutic potential of targeting the USP-ncRNA axis for cancer treatment.

Main Methods:

  • Literature review of studies investigating USP-ncRNA interactions in cancer.
  • Analysis of the roles of USPs and ncRNAs in cancer hallmarks like proliferation, apoptosis, metastasis, and angiogenesis.
  • Examination of the impact on metabolic reprogramming and immune modulation within the TME.

Main Results:

  • USPs and ncRNAs collaboratively regulate cancer cell proliferation, apoptosis, metastasis, angiogenesis, and stemness.
  • The USP-ncRNA axis influences metabolic reprogramming and immune evasion within the TME.
  • Dysregulation of specific USP-ncRNA interactions contributes to cancer aggressiveness and treatment resistance.

Conclusions:

  • The intricate relationship between USPs and ncRNAs presents a novel therapeutic target for cancer.
  • Targeting the USP-ncRNA axis holds promise for overcoming resistance to conventional cancer therapies.
  • Integrating nanotechnological delivery systems with USP-ncRNA-targeted therapies can enhance treatment efficacy.
Keywords:
Immune modulationMetabolic reprogrammingNanotechnologyNon-coding RNAs (ncRNAs)Targeting inhibitionUbiquitin-specific proteases (USPs)

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