No abstract

miR-122 has been considered both as tumor suppressor miRNA and oncomiR in breast tumor phenotypes. However, the role of miR-122 in triple-negative breast cancer (TNBC) is still unknown. In this study, the clinical value of miR-122 was used to describe the transcriptomic landscape of TNBC tumors obtained from The Cancer Genome Atlas database. Low expression levels of miR-122 were associated with poor overall survival (OS) of TNBC patients than those with higher expression levels of miR-122. We identified gene expression profiles in TNBC tumors expressed lower or higher miR-122. Gene coexpression networks analysis revealed gene modules and hub genes specific to TNBC tumors with low or high miR-122 levels. Gene ontology and KEGG pathways analysis revealed that gene modules in TNBC with gain of miR-122 were related to cell cycle and DNA repair, while in TNBC with loss of miR-122 were enriched in cell cycle, proliferation, apoptosis and activation of cell migration and invasion. The expression of hub genes distinguished TNBC tumors with gain or loss of miR-122 from normal breast tissues. Furthermore, high levels of hub genes were associated with better OS in TNBC patients. Interestingly, the gene coexpression network related to loss of miR-122 were enriched with target genes of miR-122, but this did not observed in those with gain of miR-122. Target genes of miR-122 are oncogenes mainly associated with cell differentiation-related processes. Finally, 75 genes were identified exclusively associated to loss of miR-122, which are also implicated in cell differentiation. In conclusion, miR-122 could act as tumor suppressor by controlling oncogenes in TNBC.

Gastric adenocarcinoma is the result of the progression of preneoplastic lesions in gastric mucosa. Helicobacter pylori (H. pylori) infection is the main environmental risk factor linked to the multistep progression from precancerous conditions to gastric cancer. Identification of early diagnosis biomarkers in preneoplastic lesions could prevent progression to cancer. microRNAs (miRNAs) are non-coding RNAs that have emerged as promising candidates with diagnostic and prognostic potential. miRNAs differentially expressed and functional enrichment analysis were identified in miRNomes of gastric preneoplastic samples available at the European Nucleotide Archive (ENA) and in gastric adenocarcinoma samples from TCGA databases by limma-voom linear model on the Galaxy Collections platform and R package. The prognostic value of miRNAs was evaluated by Kaplan-Meier assays. The expression level of miR-18a-5p was determined by RT-qPCR in preneoplastic lesion samples from Mexican patients positive to pathogenic H. pylori and in the H. pylori-AGS cells co-cultures. Fifteen miRNAs were progressively deregulated in the multistep gastric carcinogenesis model, and they were predictors of the outcome in gastric adenocarcinoma patients. Additionally, miR-18a-5p was significantly upregulated in gastric tumors compared to normal gastric epithelium samples and it was also associated with better overall survival in GC patients. The expression of miR-18a-5p was significantly inhibited in gastric preneoplastic lesions positive to pathogenic H. pylori. Further, miR-18a-5p was up-regulated in AGS cells infected with pathogenic H. pylori strain. In conclusion, miRNAs signature distinguished the gastric lesions through malignant transformation process, including miR-18a-5p, which was exclusively associated with H. pylori infection.