BackgroundSerous epithelial ovarian cancer (SEOC) is a highly metastatic disease and its progression has been implicated with microRNAs. This study aimed to identify the differentially expressed microRNAs in Malaysian patients with SEOC and examine the microRNAs functional roles in SEOC cells.MethodsTwenty-two SEOC and twenty-two normal samples were subjected to miRNA expression profiling using the locked nucleic acid (LNA) quantitative real-time PCR (qPCR). The localization of miR-200c was determined via LNA in situ hybridization (ISH). Functional analysis of miR-200c and miR-31 on cell proliferation, migration and invasion and clonogenic cell survival were assessed in vitro. The putative target genes of the two miRNAs were predicted by miRWalk program and expression of the target genes in SEOC cell lines was validated.ResultsThe miRNA expression profiling revealed thirty-eight significantly dysregulated miRNAs in SEOC compared to normal ovarian tissues. Of these, eighteen were up-regulated whilst twenty miRNAs were down-regulated. We observed chromogenic miR-200c-ISH signal predominantly in the cytoplasmic compartment of both epithelial and inflammatory cancer cells. Re-expression of miR-200c significantly increased the cell proliferation and colony formation but reduced the migration and invasion of SEOC cells. In addition, miR-200c expression was inversely proportionate with the expression of deleted in liver cancer-1 (DLC-1) gene. Over-expression of miR-31 in SEOC cells resulted in decreased cell proliferation, clonogenic potential, cell migration and invasion. Meanwhile, miR-31 gain-of-function led to the down-regulation of AF4/FMR2 family member 1 (AFF1) gene.ConclusionsThese data suggested that miR-200c and miR-31 may play roles in the SEOC metastasis biology and could be considered as promising targets for therapeutic purposes.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-015-0186-7) contains supplementary material, which is available to authorized users.
MicroRNA (miRNA) has emerged as a promising biomarker for improving the current state of an early lung cancer diagnosis. Multiple studies have reported that circulating miRNAs are usually combined in a single panel in determining the risk of lung cancer. In this study, we sought to identify the potential miRNAs as biomarkers for the survival of lung cancer patients. The microarray analysis was performed on the isolated miRNA samples of formalin-fixed lung cancer tissues from Malaysian populations. The correlation between miRNA expression and lung adenocarcinoma (LUAD) patient survival was predicted using TGGA data, followed by extensive in silico analyses, including miRNA target gene identification, protein-protein interaction (PPI) network construction, subnetwork (SN) detection, functional enrichment analysis, gene-disease associations, and survival analysis in advanced-stage LUAD. Overall, two promising miR-99a-5pand miR-148a-3p were upregulated in the patients with good survival. We found that 64 miR-99a-5p and 95 miR-148a-3ptarget genes were associated with poor prognosis and highly participated in cancer-associated processes, such as apoptosis, mRNA transport and cell-cell adhesion. The density score of 4.667, 3.333, and 3.000 in respective SN1, SN2, and SN3 showed the significant subnetworks of constructed PPI leading to the identification of 17 targets, of which ~79% of them involved in neoplastic diseases. Four high-confidence target genes (SUDS3, TOMM22, KPNA4, and HMGB1) were associated with worse overall survival in LUAD patients, implying their critical roles in LUAD pathogenesis. These findings shed additional light on the roles of miR-99a-5p and miR-148a-3p as potential biomarkers for LUAD survival.
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