TAR RNA-binding protein 1 (TARBP1) functions as an RNA-binding protein which holds significant regulatory influence across multiple cancer types. Research demonstrates that the expression level of TARBP1 in human hepatocellular carcinoma and non-small cell lung cancer might correlate with tumor occurrence and development as well as patient prognosis.
As an RNA-binding protein TARBP1 (TAR RNA-binding protein 1) regulates gene expression and processes both microRNA (miRNA) and RNA interference (RNAi). Research in the past few years has established that TARBP1 shows abnormal expression patterns across numerous cancer types and may drive tumor formation and growth.
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Expression of TARBP1 in Hepatocellular Carcinoma (HCC)
Increased Expression Level
Tissue samples from HCC patients reveal significant TARBP1 upregulation which appears linked to disease advancement and negative outcomes compared with healthy liver tissue.
Potential Mechanism
TARBP1 could influence cancer development through its effects on microRNA (miRNA) processing. By disrupting Dicer-mediated RNA splicing TARBP1 affects miRNA maturation, which leads to enhanced cancer cell proliferation and migration. Research indicates that TARBP1 controls PI3K/AKT and Wnt/β-catenin signaling pathways which help HCC cells survive and develop drug resistance.
Fig 1. Immunohistochemistry detection of TARBP1 protein expression (Ye, J., et al. 2015).
Mechanisms by TARBP1 Promotes Occurrence and Development of HCC
Affects Maturation of microRNA
TARBP1 functions within the Dicer complex to facilitate the maturation of microRNA (miRNA). miRNA serves as a critical regulator in cancer development and TARBP1 influences HCC progression through different mechanisms. The suppression of tumor-suppressive miRNAs (including miR-200 family members and miR-34a) stimulates both HCC cell growth and metastatic activity. The maturation process of pro-cancer miRNAs promotes oncogene expression which accelerates HCC progression.
Activate Cancer-related Signaling Pathways
TARBP1 promotes the growth and survival of HCC cells by regulating multiple key signaling pathways.
| Wnt/β-catenin pathway |
TARBP1 works to keep β-catenin stable while simultaneously driving proliferation of HCC cells and preserving their stem cell features. |
| PI3K/AKT pathway |
TARBP1 high expression triggers AKT phosphorylation which enhances anti-apoptotic functions in HCC cells and results in chemotherapy resistance. |
| EMT (epithelial-mesenchymal transition) |
Through the regulation of E-cadherin and Vimentin, TARBP1 enables HCC cells to migrate and invade. |
Promoting Tumor Microenvironment Remodeling
The tumor microenvironment of HCC becomes more invasive through TARBP1's regulation of cytokine secretion and exosomal miRNA release. For example: The process promotes inflammatory factor expression including IL-6 and TNF-α while speeding up HCC's malignant development. The interaction between cancer cells and hepatic stellate cells becomes stronger which leads to increased tumor angiogenesis and immunosuppression.
Expression of TARBP1 in Non-small Cell Lung Cancer (NSCLC)
Increased Expression Level
High TARBP1 expression in NSCLC and its subtypes lung adenocarcinoma and lung squamous cell carcinoma appears to contribute to lung cancer progression. TARBP1 expression levels that exceed typical amounts display strong connections to cancer severity traits which include tumor stage advancement as well as lymph node metastasis and tumor invasiveness among NSCLC patients.
Mechanism of Action
TARBP1 function in NSCLC appears to have a strong connection with RNA interference mechanisms and regulation of miRNA. Research demonstrates that TARBP1 encourages lung cancer cell invasion and metastasis through its regulatory effects on EMT (epithelial-mesenchymal transition). Research indicates that TARBP1 abnormal expression leads to chemotherapy resistance because it strengthens NSCLC cell resistance to drugs like cisplatin by modifying DNA damage repair processes.
Fig 2. TARBP1 expression status in paired lung cancer and adjacent normal tissues (Ye, J., et al. 2018).
Mechanisms by TARBP1 Promotes Occurrence and Development of NSCLC
Regulates Maturation of microRNA (miRNA) and Promotes Oncogene Expression
The Dicer complex includes TARBP1 which functions to mature and process miRNA molecules. TARBP1 impacts NSCLC development by aiding the maturation of pro-oncogenic miRNAs such as miR-21 and miR-155 and by boosting cancer cells' proliferation and anti-apoptotic capabilities. The suppression of tumor suppressor microRNAs including miR-34a and the miR-200 family leads to oncogene activation which increases the invasive and metastatic potential of NSCLC.
Activation of Cancer-related Signaling Pathways
The pro-oncogenic effect of TARBP1 in NSCLC may be related to the following signaling pathways:
| Wnt/β-catenin pathway |
TARBP1 may promote NSCLC cell proliferation, maintenance of stem cell characteristics, and drug resistance by stabilizing β-catenin. |
| PI3K/AKT/mTOR pathway |
High expression of TARBP1 may promote AKT phosphorylation, increase the survival rate of NSCLC cells, and enhance their tolerance to chemotherapeutic drugs. |
| EMT (epithelial-mesenchymal transition) |
TARBP1 may promote the migration and invasion ability of NSCLC cells and improve their metastatic potential by downregulating E-cadherin and upregulating Vimentin. |
Affecting Tumor Microenvironment and Promoting Immune Escape
Through its control over cytokine expression TARBP1 helps create an immunosuppressive microenvironment enabling NSCLC cells to avoid immune detection. Research indicates that TARBP1 influences exosomal miRNA secretion which alters tumor cell communication and enhances cancer cell survival.
TARBP1 Highly Expressed in Cancer and Expected a New Target
HCC cells show high levels of TARBP1 expression which drives tumor development and progression via miRNA processing and activation of signaling pathways along with EMT promotion. The elevated presence of TARBP1 correlates with unfavorable outcomes in HCC patients while serving as a prospective diagnostic and prognostic marker for HCC which may develop into a targeted treatment approach for the disease.
TARBP1 expression is elevated in NSCLC and drives cancer progression by modifying miRNA maturation alongside activating oncogenic signaling pathways and fostering EMT and tumor microenvironment changes. TARBP1 high expression correlates with poor NSCLC prognosis while functioning as a prospective biomarker and therapeutic target.
TARBP1 shows high expression levels in hepatocellular carcinoma (HCC) and non-small cell lung cancer (NSCLC) where it promotes tumor progression through miRNA maturation regulation and cell signaling pathway modulation while driving EMT. TARBP1 functions as a potential biomarker for HCC and NSCLC and also presents as a promising target for RNA-targeted therapy development.
References
- Ye, J., et al. Expression of protein TARBP1 in human hepatocellular carcinoma and its prognostic significance. International Journal of Clinical and Experimental Pathology. 2015, 8(8): 9089.
- Ye, J., et al. Expression of TARBP1 protein in human non-small-cell lung cancer and its prognostic significance. Oncology letters. 2018, 15(5): 7182-7190.
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