AUTHOR=Zhang Yuting , Qin Peifang , Xu Xingfeng , Li Mao , Huang Haitao , Yan Jianguo , Zhou Yali 

TITLE=Mediator Complex Subunit 19 Promotes the Development of Hepatocellular Carcinoma by Regulating the AKT/mTOR Signaling Pathway

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.792285

DOI=10.3389/fonc.2021.792285

ISSN=2234-943X

ABSTRACT=<sec><title>Background</title><p>Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, the pathogenesis of which remains unclear. Mediator complex subunit 19 (<italic>MED19</italic>), 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 <italic>MED19</italic> in HCC and elucidate its mechanism.</p></sec><sec><title>Methods</title><p><italic>MED19</italic> expression in HCC tissues was determined. The relationship between <italic>MED19</italic> and the clinical prognosis was explored. The influence of <italic>MED19</italic> on HCC cell viability, migration, invasion, and apoptosis was studied. The expression of <italic>AKT/mTOR</italic> pathway genes and proteins was detected by qRT-PCR and western blot. The correlation between <italic>MED19</italic> and immune infiltration was investigated.</p></sec><sec><title>Results</title><p><italic>MED19</italic> was upregulated in HCC tissues compared with tumor-adjacent tissues, and was associated with a poor prognosis. Furthermore, high <italic>MED19</italic> expression was correlated with race, gender, <italic>etc.</italic> Knockdown of <italic>MED19</italic> inhibited cell proliferation, migration, invasion, and promoted apoptosis. Knockdown of <italic>MED19</italic> decreased <italic>p-AKT</italic> and <italic>p-mTOR</italic> protein expression. Additionally, the downstream effectors of the <italic>AKT/mTOR</italic> pathway, <italic>p70S6K1</italic> and <italic>4EBP1</italic>, were affected by <italic>MED19</italic>. Notably, <italic>MED19</italic> expression was positively correlated with the infiltration levels of B cells, CD4<sup>+</sup> T cells, CD8<sup>+</sup> T cells, macrophages, <italic>etc.</italic></p></sec><sec><title>Conclusion</title><p><italic>MED19</italic> is significantly upregulated in HCC tissues and cells. <italic>MED19</italic> may promote the progression of HCC <italic>in vitro</italic> and may be related to immune infiltration. Together, our data show that <italic>MED19</italic> could be considered as a new possible biomarker as well as a novel therapeutic target for HCC.</p></sec>