Mitoribosome Defect in Hepatocellular Carcinoma Promotes an Aggressive Phenotype with Suppressed Immune Reaction.
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ABSTRACT:
SUBMITTER: Kwon SM
PROVIDER: S-EPMC7306587 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
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Project description:Background and objectivesThe roles of microRNA(miR)-106b-5p in hepatocellular carcinoma (HCC) remain unclear. We aimed here to investigate the clinical significance of miR-106b-5p expression in HCC and its underlying mechanisms.MethodsExpression levels of miR-106b-5p in 108 HCC clinical samples by quantitative real-time reverse transcription PCR. Associations of miR-106b-5p expression with various clinicopathological features and patients' prognosis were evaluated by Chi-square test, Kaplan-Meier, and Cox proportional regression analyses, respectively. The target gene of miR-106b-5p and their functions in HCC cells were investigated by luciferase reporter, CCK-8, and Transwell Matrigel invasion assays.ResultsmiR-106b-5p expression was markedly higher in HCC tissues than in noncancerous adjacent liver tissues (P < .001). miR-106b-5p upregulation was significantly associated with advanced TNM stage (P = .02), short recurrence-free (P = .005), and overall (P = .001) survivals. Importantly, miR-106b-5p expression was an independent predictor of poor prognosis (P < .05). RUNX3 was identified as a direct target gene of miR-106b-5p in HCC cells. Functionally, miR-106b-5p upregulation promoted the viability and invasion of HCC cells, while enforced RUNX3 expression reversed the oncogenic effects of miR-106b-5p overexpression.ConclusionsmiR-106b-5p may serve as a potent prognostic marker for tumor recurrence and survival of HCC patients. miR-106b-5p may exert an oncogenic role in HCC via regulating its target gene RUNX3.
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Project description:Immunotherapies are promising approaches for treating hepatocellular carcinomas (HCCs) refractory to conventional therapies. However, a recent clinical trial of immune checkpoint inhibitors (ICIs) revealed that anti-tumor responses to ICIs are not satisfactory in HCC cases. Therefore, it is critical to identify molecular markers to predict outcome and develop novel combination therapies that enhance the efficacy of ICIs. Recently, several attempts have been made to classify HCC based on genome, epigenome, and transcriptome analyses. These molecular classifications are characterized by unique clinical and histological features of HCC, as well immune phenotype. For example, HCCs exhibiting gene expression patterns with proliferation signals and stem cell markers are associated with the enrichment of immune infiltrates in tumors, suggesting immune-proficient characteristics for this type of HCC. However, the presence of activating mutations in β-catenin represents a lack of immune infiltrates and refractoriness to ICIs. Although the precise mechanism that links the immunological phenotype with molecular features remains controversial, it is conceivable that alterations of oncogenic cellular signaling in cancer may lead to the expression of immune-regulatory molecules and result in the acquisition of specific immunological microenvironments for each case of HCC. Therefore, these molecular and immune characteristics should be considered for the management of HCC using immunotherapy.
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