The Transforming growth factor β regulator 4 protein (TBRG4) has become a focus of research as a potential biomarker for multiple cancer types in the past few years. Research indicates TBRG4 significantly influences hepatocellular carcinoma (HCC), oral squamous cell carcinoma (OSCC) and pancreatic cancer (PC) development while providing a potential diagnostic and therapeutic target with prognostic value.
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TBRG4 Demonstrates Physiological Activity in Cellular Processes
The RNA-binding protein Transforming Growth Factor β Regulator 4 (TBRG4) serves as a critical component in cell proliferation, differentiation, apoptosis, and RNA metabolism processes. The regulation of the TGF-β signaling pathway together with RNA metabolism by TBRG4 influences multiple physiological and pathological mechanisms which affect cancer development and occurrence.
The Role of TBRG4 in Cell Function
The RNA-binding protein TBRG4 influences the expression of genes related to cell proliferation through its regulation of mRNA stability and translation. Research indicates that TBRG4 functions as a regulator of the cell cycle by influencing the G1/S and G2/M phase transitions. The protein can work through the p53 signaling pathway to control both cell growth and differentiation. TBRG4 seems to influence the cell apoptosis pathway during both DNA damage responses and oxidative stress situations. It controls anti-apoptotic gene expression (notably the BCL-2 family) which subsequently influences cell survival.
The Role of TBRG4 RNA Metabolism
Through its function as an RNA-binding protein TBRG4 binds to the mRNA 3' UTR to modulate mRNA stability for specific genes while influencing their degradation or translation efficiency. TBRG4 participates in ribosomal RNA (rRNA) processing which impacts ribosome biogenesis. The regulation of non-coding RNA (ncRNA) interacts with both miRNA and lncRNA to participate in the post-transcriptional regulation process.
The Role of TBRG4 TGF-β Signaling Pathway
The TBRG4 protein influences the TGF-β signaling pathway through its regulation of TGF-β receptors (TGFBR1/2) and downstream effector molecules like SMADs. The TGF-β signaling pathway controls cell growth and differentiation as well as immune response regulation while TBRG4 has the potential to modify cellular behavior through this signaling route. The TGF-β signaling pathway functions as a central regulator in both epithelial-mesenchymal transition (EMT) and tissue fibrosis processes.
Potential Role of TBRG4 in Diseases
Cancer
TBRG4 is highly expressed in various cancers such as hepatocellular carcinoma (HCC), oral squamous cell carcinoma (OSCC), and pancreatic cancer (PC), and may promote tumor progression. It may promote tumor invasion and metastasis through RNA metabolic regulation, TGF-β signaling pathway, and EMT. It may affect drug resistance, such as chemotherapy or radiotherapy tolerance.
Fibrotic Diseases
Since the TGF-β signaling pathway plays a key role in tissue fibrosis, TBRG4 may affect the progression of diseases such as liver fibrosis and pulmonary fibrosis by regulating this pathway.
Immune and Metabolic Diseases
It may affect TGF-β-mediated immune regulation and may have a potential role in autoimmune diseases (such as rheumatoid arthritis and systemic lupus erythematosus). It may affect metabolism-related genes and has a regulatory role in metabolic diseases such as diabetes and fatty liver.
Role of TBRG4 in HCC
Hepatocellular Carcinoma (HCC) tissues show high levels of TBRG4 expression which may link to tumor proliferation as well as invasion and metastasis processes. The TGF-β signaling pathway regulation by TBRG4 leads to increased HCC cell growth and altered chemotherapy resistance within these cells. TBRG4 has been linked to negative outcomes in HCC patients and holds promise as a prognostic biomarker.
Fig 1. TBRG4 is abnormally highly expressed in HCC cell lines and tissue samples (Tao, S., et al. 2024).
The Function of TBRG4 Protein Within Oral Squamous Cell Carcinoma (OSCC) Tissues
TBRG4 expression levels increase dramatically within oral squamous cell carcinoma tissues while exhibiting strong connections to cancer cell growth, invasion potential, and resistance to chemotherapy. The mechanism works to support cancer cell growth and spread while preventing programmed cell death. The protein TBRG4 which binds RNA could influence RNA metabolism and transcription control within cancerous cells. TBRG4 may enable OSCC cell migration and invasion through the regulation of TGF-β and EMT-related genes. This element influences cancer cell metabolic functions and strengthens its capacity to endure hypoxic conditions or extreme environments. The PI3K/AKT/mTOR signaling pathway may work with this protein to boost cancer cell growth.
Role of TBRG4 in Pancreatic Cancer (PC)
Pancreatic cancer tissues and cell lines exhibit a significant elevation of TBRG4 expression which correlates with tumor progression and increased invasiveness as well as drug resistance. TBRG4 influences pancreatic cancer cell RNA metabolism and engages with the TGF-β pathway to boost cancer cell survival and migration. Pancreatic cancer patients who have high levels of TBRG4 expression typically face worse prognoses. This process increases the expression of oncogenes including MYC while simultaneously boosting tumor cell proliferation capacity. The growth patterns and resistance to drugs in cancer cells may change through mechanisms that manage RNA metabolism including mRNA stability.
Potential of TBRG4 as a Cancer Biomarker
Diagnostic marker: TBRG4 expression levels provide an effective method for identifying HCC as well as OSCC and PC while enhancing early diagnosis precision.
Prognostic marker: Patients with elevated TBRG4 levels generally experience worse survival outcomes which makes TBRG4 a valuable tool for evaluating patient prognosis.
Therapeutic target: Researchers could develop innovative cancer treatment strategies by targeting TBRG4-related pathways which include the TGF-β signaling pathway.
TBRG4 Function as Both a Diagnostic Marker and a Therapeutic Target
TBRG4 functions as an RNA-binding protein that is crucial for RNA metabolism and influences cell proliferation along with apoptosis and migration as well as the regulation of TGF-β signaling. The elevated expression of this substance appears to correlate with cancer development as well as fibrotic diseases and immune system irregularities. Additional research could disclose more physiological functions of TBRG4 as well as its potential clinical applications as a marker or therapeutic target. TBRG4 functions as a new biomarker for hepatocellular carcinoma (HCC), oral squamous cell carcinoma (OSCC) and pancreatic cancer (PC) which may become essential for early cancer diagnosis and targeted treatment options while assessing prognosis. Upcoming research should disclose more details about its molecular function and assess its clinical application possibilities.
References
- Ramasubramanian, A., et al. High expression of novel biomarker TBRG4 promotes the progression and invasion of oral squamous cell carcinoma. Journal of Oral Pathology & Medicine. 2023, 52(8): 738-745.
- Tao, S., et al. High expression of TBRG4 in relation to unfavorable outcome and cell ferroptosis in hepatocellular carcinoma. BMC cancer. 2024, 24(1): 194.
- Wang, A., et al. Knockdown of TBRG4 affects tumorigenesis in human H1299 lung cancer cells by regulating DDIT3, CAV1 and RRM2. Oncology letters. 2018, 15(1): 121-128.
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