Bladder cancer cells with highlighted CIRBP proteins.

Bladder Cancer Breakthrough: Can CIRBP Become Our Next Target?

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Theo Raines in Health & Wellness August 2025 • 4 min read.

"New research unveils CIRBP as a key player in bladder cancer, opening doors for innovative treatments and improved patient outcomes."


Bladder cancer, ranking as the ninth most common malignancy globally, presents a significant challenge with an estimated 429,000 new cases and 165,000 deaths annually. Recent research has been dedicated to unraveling the molecular pathways that drive its progression, including the RAS-mitogen-activated protein kinase (MAPK) pathway, Wnt/β-catenin signaling, and epithelial-mesenchymal transition (EMT).

In a groundbreaking study, researchers have identified cold-inducible RNA binding protein (CIRBP) as a novel oncogene in bladder cancer. CIRBP, originally identified in the testis as a mammalian cold shock protein, is induced by various cellular stresses, including UV radiation, cold, and hypoxia. Prior research has linked CIRBP to tumorigenesis in prostate, colon, breast, and skin cancers, highlighting its potential role in cancer development.

The new study demonstrates that CIRBP is overexpressed in bladder cancer tissues and cell lines, promoting proliferation and migration. It also induces the expression of HIF-1α by binding to the 3'-UTR of its mRNA, increasing mRNA stability. This mechanism sheds light on how CIRBP influences the aggressive behavior of bladder cancer cells, marking it as a promising target for future therapies.

How Does CIRBP Fuel Bladder Cancer?

Bladder cancer cells with highlighted CIRBP proteins.

The research reveals that CIRBP promotes bladder cancer progression by several key mechanisms:

Increased Cell Proliferation and Migration: CIRBP overexpression significantly enhances the proliferation and migration of bladder cancer cells. This was confirmed through MTT assays, clonogenic survival assays, and transwell migration assays, demonstrating its critical role in tumor growth and spread.

  • Upregulation of HIF-1α: CIRBP binds to the 3'-UTR of HIF-1α mRNA, increasing its stability and translation. HIF-1α is a major regulator that promotes cancer progression by activating various oncogenes.
  • MAPK Pathway Activation: CIRBP increases the phosphorylation state of ERK1/2 and p38, key components of the MAPK signaling pathway, which is crucial for cell proliferation, differentiation, and survival.
  • Epithelial-Mesenchymal Transition (EMT): CIRBP promotes EMT by altering the expression of EMT markers. Knockdown of CIRBP upregulates E-cadherin (an epithelial marker) and suppresses N-cadherin, vimentin, β-catenin, and snail (mesenchymal markers).
These findings were further validated in vivo using xenograft models. The study found that reducing CIRBP expression significantly slowed tumor growth and metastasis in mice, underscoring its importance in bladder cancer pathogenesis. These discoveries position CIRBP as a pivotal target for novel therapeutic interventions.

The Future of CIRBP-Targeted Therapies

This study paves the way for developing targeted therapies that inhibit CIRBP, potentially revolutionizing bladder cancer treatment. By understanding CIRBP's role in promoting cell proliferation, migration, and metastasis, researchers can design interventions that disrupt these processes. Future studies will focus on identifying small molecule inhibitors or RNA-based therapies that specifically target CIRBP, offering new hope for patients with bladder cancer. Targeting CIRBP could lead to more effective and less toxic treatments, improving survival rates and quality of life for those affected by this challenging disease.

About this Article -

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Everything You Need To Know

1

What exactly is CIRBP, and what role does it play in cancer?

CIRBP, or cold-inducible RNA binding protein, is a protein that is induced by cellular stresses such as UV radiation, cold, and hypoxia. It was originally identified in the testis as a mammalian cold shock protein. Research indicates that CIRBP functions as an oncogene in bladder cancer, meaning it promotes the development and progression of the disease. CIRBP has been linked to tumorigenesis in other cancers like prostate, colon, breast and skin cancers.

2

How does CIRBP contribute to the progression of bladder cancer?

CIRBP significantly influences bladder cancer progression through multiple mechanisms. It enhances cell proliferation and migration, upregulates HIF-1α expression by increasing its mRNA stability, activates the MAPK signaling pathway by increasing phosphorylation of ERK1/2 and p38, and promotes Epithelial-Mesenchymal Transition (EMT) by altering the expression of EMT markers such as E-cadherin, N-cadherin, vimentin, β-catenin and snail.

3

What is HIF-1α, and how does CIRBP affect its function in bladder cancer?

HIF-1α, or hypoxia-inducible factor 1-alpha, is a major regulator that promotes cancer progression by activating various oncogenes. CIRBP binds to the 3'-UTR of HIF-1α mRNA, increasing its stability and translation. This upregulation of HIF-1α by CIRBP is critical because HIF-1α activation leads to the expression of genes that help cancer cells survive in low-oxygen environments, promote angiogenesis (formation of new blood vessels), and increase cell proliferation and metastasis.

4

What is the MAPK pathway, and how is it related to CIRBP's influence on bladder cancer?

The MAPK (mitogen-activated protein kinase) pathway is a crucial signaling pathway involved in cell proliferation, differentiation, and survival. CIRBP increases the phosphorylation state of ERK1/2 and p38, which are key components of the MAPK signaling pathway. By activating the MAPK pathway, CIRBP promotes the uncontrolled growth and survival of bladder cancer cells.

5

What is EMT, and how does CIRBP affect this process in bladder cancer cells?

EMT, or epithelial-mesenchymal transition, is a process where epithelial cells lose their cell polarity and cell-cell adhesion, and gain migratory and invasive properties. CIRBP promotes EMT by altering the expression of EMT markers. Specifically, CIRBP knockdown upregulates E-cadherin (an epithelial marker) and suppresses N-cadherin, vimentin, β-catenin, and snail (mesenchymal markers). This shift allows cancer cells to detach from the primary tumor and spread to other parts of the body, contributing to metastasis.

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