Alteration of the microRNA expression profile in human osteosarcoma cells transfected with APE1 siRNA

Abstract

Apurinic/apyrimidinic endonuclease1 (APE1), which has the dual functions of DNA repair and redox regulation, is considered to be a promising potential target in cancer treatment. Microarray and qRT-PCR were used to confirm the change of miRNA followed by analysis with comprehensive bioinformatics-based analysis. Both microarray and qRT-PCR demonstrated that 13 microRNAs (miRNAs) were significantly changed (>2-fold) in APE1 knockdown HOS cells; seven of them (hsa-miR-451, hsa-miR-1290, hsa-miR-765, hsa-miR-483-5p, hsa-miR-513a-5p, hsa-miR-129-5p and hsa-miR-31) were up-regulated and the other six (hsa-miR-29b, hsa-miR-197, has-let-7b, hsa-miR-324-5p, hsa-let-7i and hsa-miR-484) were down-regulated. Furthermore, pathway analysis showed that these miRNAs and their target genes affected by the expression of APE1 were involved in pathways relating to developmental processes, regulation of cellular processes, cell signaling (such as TGF-β, Wnt, MAPK and the p53 signaling pathway) and cancers. There are putative binding sites of NF-κB, p53, HIF-1α, AP-1, PEBP2, ATF, NF-Y, Pax-2,CREB and c-Myb in the promoters of several down regulated miRNAs, indicating that APE1 may regulate miRNAs via transcription factors. Our data suggest that our understanding of the biological functions of APE1 will inevitably expand due to the novel pathways that APE1 uses to regulate gene expression through miRNAs.

MicroRNA-197 influences 5-fluorouracil resistance via thymidylate synthase in colorectal cancer

“…Recently, miR-197 has been identified as an oncomiR in hepatocellular carcinoma [20], non-small-cell lung cancer [21], pancreatic cancer [22] and male breast cancer [23]. However, other studies revealed that miR-197 was down-regulated in esophageal cancer [24], oral carcinoma [25], gastric carcinoma [26], osteosarcoma [27] and astrocytomas [28], and might exert an anti-cancer effect on these cancers. This discrepancy may be attributed to the distinct miRNA signatures of organ/tissue-specificity and temporal expression patterns.…”

Unveiling the non-repair face of the Base Excision Repair pathway in RNA processing: A missing link between DNA repair and gene expression?

“…As a supplementary indirect observation, it has been recently found that APE1 down-regulation is associated with alteration in miRNAs expression, which are involved in pathways relating to developmental and regulation of cellular processes, cell signaling and cancer [96].…”

Downregulation of the DNA repair enzyme apurinic/apyrimidinic endonuclease 1 stimulates transforming growth factor-β1 production and promotes actin rearrangement

“…4D); the The aim of this study was to elucidate the effect of APE1 downregulation on ECM-related downregulation affected the expression of various microRNAs, including miR-29b [22].…”