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Knock-down of ubiquitin-specific protease 22 by micro-RNA interference inhibits colorectal cancer growth

Hui Xu1, Yan-Long Liu, Yan-Mei Yang

  • 1Department of Oncosurgery, The Affiliated 4th Hospital of Harbin Medical University, 37 Yiyuan Street, Nangang District, Harbin, 150001, People's Republic of China.

International Journal of Colorectal Disease
|July 21, 2011
PubMed
Abstract

Insights

Targeting ubiquitin-specific protease 22 (USP22) may inhibit colorectal cancer growth. Suppressing USP22 with micro-interfering RNA (miRNA) reduced cell proliferation and tumor growth in mice, suggesting USP22 as a potential cancer therapy target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Ubiquitin-specific protease 22 (USP22) is implicated in epithelial malignancies and solid tumors.
  • USP22 functions as a cancer stem cell marker, indicating its potential as a therapeutic target.
  • Understanding USP22's role in colorectal cancer is crucial for developing novel treatment strategies.

Purpose of the Study:

  • To investigate the functional role of USP22 in the human colorectal cancer cell line HCT116.
  • To suppress USP22 expression using micro-interfering RNA (miRNA) and assess its effects on cancer progression.
  • To evaluate USP22 as a potential therapeutic target for colorectal cancer.

Main Methods:

  • USP22 expression was suppressed in HCT116 cells using miRNA.
  • Cellular proliferation, cell cycle, and apoptosis were analyzed post-USP22 knockdown.
  • A tumor xenograft model in nude mice was utilized to assess the in vivo effects of USP22 inhibition.
  • Immunohistochemical staining was performed to evaluate USP22 expression in tumor tissues.

Main Results:

  • USP22 knockdown significantly inhibited cellular proliferation and induced G1 phase cell cycle arrest.
  • Apoptosis was reduced, and Major Vault Protein (MVP) expression was downregulated following USP22 suppression.
  • In vivo studies demonstrated suppressed tumor growth in mice treated with USP22 miRNA silencing vector.
  • Immunohistochemistry confirmed decreased USP22 expression in tumors after miRNA intervention.

Conclusions:

  • USP22 plays a critical role in colorectal tumor formation and growth, partly through regulating cell proliferation via a USP22-dependent pathway.
  • USP22 acts as a transcriptional factor regulating the drug-resistant gene MVP.
  • Targeting USP22 presents a promising therapeutic strategy for colorectal cancer and potentially other malignancies.

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