ABSTRACT
OBJECTIVE: Although chemotherapy is one of the first line clinical treatment of tumors, the efficacy of chemotherapy has been severely restricted by the frequent occurrence of drug resistance phenomenon. Multiple studies found that miRNAs can regulate the chemosensitivity of tumor cells. Here, this study aimed to assess the potential role of the miR-15a-5p/cell division cycle-related protein 4 (CDCA4) axis in breast cancer (BC) resistance to Adriamycin. METHODS: In the present study, the relative expression of miRNA-15a-5p in MCF-7/ADR, MCF-7 and Hs578Bst was measured by qRT-PCR. MCF-7/ADR cells underwent transfection with an miR-15a-5p mimic and inhibitor, respectively. Transwell assays, flow cytometry and CCK8 were performed to examine the potential effects of the abnormal expression of miR-15a-5p. The association of aberrant miR-15a-5p expression with Adriamycin resistance in BC was determined in cultured MCF-7/ADR cells. Bioinformatics was employed to predict the genes targeted by miR-15a-5p. Moreover, the correlation between miR-15a-5p and its target gene, CDCA4, was evaluated based on qRT-PCR data. RESULTS: The expression of miR-15a-5p was significantly downregulated in MCF/ADR cells compared with MCF-7 and Hs578Bst cell lines. In the presence of Adriamycin, miR-15a-5p overexpression significantly increased cell chemosensitivity, as well as MCF-7/ADR cell proliferation, invasion, and migration, while promoting apoptosis and inducing cell-cycle arrest in the synthesis phase. CDCA4 RNA interference enhanced these effects as shown in our previous study. Bioinformatics identified CDCA4 as an miR-15a-5p target gene. qRT-PCR further demonstrated that CDCA4 and miR-15a-5p expression levels were inversely correlated. CONCLUSION: Adriamycin resistance in BC cells was, at least in part, altered by mRNA-15a-5p via regulation of its target gene, CDCA4, by controlling the cell cycle, which may provide some novel ideas for BC chemotherapy in the future.
ABSTRACT
Prostate cancer (CaP) is a serious and common genital tumor. Generally, men with metastatic CaP can easily develop castrationresistant prostate cancer (CRPC). However, the pathogenesis and tumorigenic pathways of CRPC remain to be elucidated. The present study performed a comprehensive analysis on the gene expression profile of CRPC in order to determine the pathogenesis and tumorigenic of CRPC. The GSE33316 microarray, which consisted of 5 noncastrated samples and 5 castrated samples, was downloaded from the gene expression omnibus database. Subsequently, 201 upregulated and 161 downregulated differentially expressed genes (DEGs) were identified using the limma package in R and those genes were classified and annotated by plugin Mcode of Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using Database for Annotation, Visualization and Integrated Discovery and KEGG Orthology Based Annotation System 2.0 online tools to investigate the function of different gene modules. The BiNGO tool was used to visualize the level of enriched GO terms. Proteinprotein interaction network was constructed using STRING and analyzed with Cytoscape. In conclusion, the present study determined that aldoketo reductase 3, cyclin B2, regulator of G protein signaling 2, nuclear factor of activated Tcells and protein kinase C a may have important roles in the development of CRPC.
