Abstract
BackgroundHepatocellular carcinoma (HCC) is one of the most common malignant tumors, the pathogenesis of which remains unclear. Mediator complex subunit 19 (MED19), a subunit of the Mediator complex, is a multi-protein co-activator necessary for DNA transcription factors to induce RNA polymerase II transcription. In the current study, we aimed to study the role of MED19 in HCC and elucidate its mechanism.Methods MED19 expression in HCC tissues was determined. The relationship between MED19 and the clinical prognosis was explored. The influence of MED19 on HCC cell viability, migration, invasion, and apoptosis was studied. The expression of AKT/mTOR pathway genes and proteins was detected by qRT-PCR and western blot. The correlation between MED19 and immune infiltration was investigated.Results MED19 was upregulated in HCC tissues compared with tumor-adjacent tissues, and was associated with a poor prognosis. Furthermore, high MED19 expression was correlated with race, gender, etc. Knockdown of MED19 inhibited cell proliferation, migration, invasion, and promoted apoptosis. Knockdown of MED19 decreased p-AKT and p-mTOR protein expression. Additionally, the downstream effectors of the AKT/mTOR pathway, p70S6K1 and 4EBP1, were affected by MED19. Notably, MED19 expression was positively correlated with the infiltration levels of B cells, CD4+ T cells, CD8+ T cells, macrophages, etc. Conclusion MED19 is significantly upregulated in HCC tissues and cells. MED19 may promote the progression of HCC in vitro and may be related to immune infiltration. Together, our data show that MED19 could be considered as a new possible biomarker as well as a novel therapeutic target for HCC.
Highlights
Hepatocellular carcinoma (HCC) is the most common primary malignancy of hepatocytes and serves as the third leading cause of cancer-related death worldwide [1].The treatment of HCC is limited
We show that Mediator complex subunit 19 (MED19) is upregulated in HCC tissues and that MED19 upregulation was closely correlated with a poor prognosis
Using Tumor Immune Estimation Resource (TIMER) 2.0, MED19 was shown to be highly expressed for bladder urothelial carcinoma (BLCA), breast cancer (BRCA), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD) and other types in the TCGA project (Figure 1A)
Summary
Hepatocellular carcinoma (HCC) is the most common primary malignancy of hepatocytes and serves as the third leading cause of cancer-related death worldwide [1].The treatment of HCC is limited. Researchers and clinicians must elucidate the molecular mechanisms of the occurrence, development, invasion, and metastasis of HCC to find and develop new therapeutic targets. Mediator is an evolutionarily conserved multi-protein complex [5, 6]. As an important part of the transcription mechanism of eukaryotes, the Mediator complex participates in gene expression and mediates the interaction between different proteins [7,8,9]. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, the pathogenesis of which remains unclear. We aimed to study the role of MED19 in HCC and elucidate its mechanism
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