USP52 impedes malignant progression and cell stemness in prostate cancer by deubiquitinating RBM5 to down-regulate

Hongliang Wu1, Sheng Wang1, Shuai Yang1

  • 1Department of Urology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China.

Insights

Ubiquitin-specific protease 52 (USP52) suppresses prostate cancer (PCa) progression and stemness by stabilizing RBM5 and reducing NCAPG2. USP52 represents a potential therapeutic target for PCa treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Ubiquitin-specific protease 52 (USP52) is implicated in cancer progression via deubiquitination.
  • The specific role and mechanism of USP52 in prostate cancer (PCa) remain largely uncharacterized.
  • Understanding USP52's regulation of key proteins like RBM5 and NCAPG2 is crucial for PCa research.

Purpose of the Study:

  • To investigate the functional regulation of USP52 in prostate cancer (PCa) development and stemness.
  • To elucidate the interplay between USP52, RNA binding motif protein 5 (RBM5), and non-SMC condensin II complex subunit G2 (NCAPG2) in PCa.
  • To determine USP52's potential as a therapeutic target for PCa.

Main Methods:

  • Quantitative reverse transcription PCR (RT-qPCR) and Western blotting for expression analysis.
  • In vitro assays including proliferation (colony formation, EdU), migration (wound healing), invasion (Transwell), and stemness (sphere formation).
  • In vivo xenograft tumor assays, co-immunoprecipitation for ubiquitination, and dual-luciferase reporter assays for protein interactions.

Main Results:

  • USP52 was aberrantly downregulated in PCa samples and cells.
  • Overexpression of USP52 significantly suppressed PCa cell proliferation, migration, invasion, and stemness, and inhibited tumor growth in vivo.
  • USP52 stabilized RBM5 by deubiquitination and repressed NCAPG2 expression, thereby inhibiting PCa progression and stemness.

Conclusions:

  • USP52 acts as a tumor suppressor in prostate cancer.
  • USP52 inhibits PCa progression and stemness by deubiquitinating RBM5, leading to the downregulation of NCAPG2.
  • USP52 demonstrates significant potential as a therapeutic target for prostate cancer.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.4K
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
38.9K
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
4.9K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
5.1K
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

1.7K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.2K