No abstract

Hepatocellular carcinoma (HCC) is generally considered one of the most common gastrointestinal malignant tumors, characterized by high invasiveness and metastatic rate, as well as insidious onset. A relationship between carcinogenicity and aberrant microRNA-139-5p (miR-139-5p) expression has been identified in multiple tumors while the specific molecular mechanisms of miR-139-5p in HCC have not yet been thoroughly elucidated. A meta-analysis of available data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, ArrayExpress and Oncomine databases, as well as the published literature, was comprehensively conducted with the aim of examining the impact of miR-139-5p expression on HCC. Additionally, predicted downstream target genes were confirmed using a series of bioinformatics tools. Moreover, a correlative biological analysis was performed to ascertain the precise function of miR-139-5p in HCC. The results revealed that the expression of miR-139-5p was noticeably lower in HCC compared with non-tumor liver tissues according to the pooled standard mean difference, which was-0.84 [95% confidence interval (CI):-1.36 to-0.32; P<0.001]. Furthermore, associations were detected between miR-139-5p expression and certain clinicopathological characteristics of TCGA samples, including tumor grade, pathological stage and T stage. Moreover, the pooled hazard ratio (HR) for overall survival (HR=1.37; 95% CI: 1.07-1.76; P=0.001) indicated that decreased miR-139-5p expression was a risk factor for adverse outcomes. Additionally, 382 intersecting genes regulated by miR-139-5p were obtained and assembled in signaling pathways, including 'transcription factor activity, sequence-specific DNA binding', 'pathways in cancer' and 'Ras signaling pathway'. Notably, four targeted genes that were focused in 'pathways in cancer' were identified as hub genes and immunohistochemical staining of the proteins encoded by these four hub genes in liver tissues, explored using the Human Protein Atlas database, confirmed their expression patterns in HCC and normal liver tissues Findings of the present study suggest that reduced miR-139-5p expression is capable of accelerating tumor progression and is associated with a poor clinical outcome by modulating the expression of downstream target genes involved in tumor-associated signaling pathways.

Tumor recurrence following radiofrequency ablation (RFA) treatment in liver cancer is an important factor affecting patient prognosis. Furthermore, the biological role of long non-coding RNAs (lncRNAs) in residual hepatoblastoma (HB) tissues after RFA remains largely unknown. By using microarray technology, this study investigated the expression of lncRNAs and mRNAs among four pairs of HB tissues (incomplete ablation treatment and no treatment) in a nude mouse subcutaneous xenograft model. Subsequently, bioinformatics analysis was used to understand the functions and pathways of the identified mRNAs. Finally, a connectivity map (CMap) analysis was conducted to identify potential therapeutic strategies for residual HB tissues. Compared with the untreated nude mouse subcutaneous xenograft model, in the experimental group, a significant difference in the expression of 740 lncRNAs and 663 mRNAs was detected. Subsequently, bioinformatics analysis revealed that the differentially expressed mRNAs were significantly enriched in pathways associated with antigen processing, the presentation of endogenous antigens, the regulation of cellular metabolic processes, MAPK signaling and cell cycle regulation. Additionally, six compounds (valproic acid, metformin, tanespimycin, wortmannin, fulvestrant and MK-886) were identified by CMap analysis as potential therapeutic agents for the treatment of residual HB tissues. These findings provide a novel insight into the pathogenesis of residual HB and potential therapeutic strategies for aggressive tumor recurrence following RFA treatment in patients with HB.