Microrna-1285 Might Potentially Regulate OCT4 Gene Expression By Direct Targeting of Its Promoter - Microrna-1285 Might Potentially Regulate OCT4 Gene Expression By Direct Targeting of Its Promoter - Open Access Pub

The human OCT4 gene encodes a transcription factor that maintains pluripotency and self-renewal in Embryonic Stem (ES) cells. This gene generates several known transcripts by alternative promoter and alternative splicing (OCT4A, OCT4B and OCT4B1). Even though OCT4A is the main isoform responsible for stemness properties, several recent controversial studies claimed that this isoform is expressed in cancer cell lines and differentiated cells, in addition to the ES cells. Our in silico studies revealed that OCT4A promoter has a completely match binding site for hsa-miR-1285. This microRNA was detected in the human embryonic stem cells for the first time and further studies showed that miR-1285 can target some tumor suppressor genes,(TSGs), such as p53, and oncogenic genes, such as TGM2. Additional bioinformatics analysis of short RNA sequencing data from ENCODE cell lines showed that miR-1285 is expressed in different cancer cell lines and differentiated cells. In this study, we supposed that miR-1285 potentially can bind to the OCT4 promoter and might regulate transcription of the OCT4 in the human cancer cell lines and differentiated cells. DOI10.14302/issn.2574-4372.jesr-15-768 OCT4 (known as POU5F1 and OCT3/4) is a key transcription factor in maintaining pluripotency and self-renewal in human and mouse embryonic stem (ES) cells 1, 2, 3, 4. This gene encodes at least three transcripts, designated as OCT4A, OCT4B and OCT4B1, by alternative splicing and alternative promoter mechanisms 5, 6, 7, 8. The Transcription Start Site (TSS) of OCT4A is located in upstream of exon1, but the OCT4B and OCT4B1 variants are transcribed from an alternative promoter in interon1 of oct4 gene 8. The OCT4A is localized in the nucleus of ES cells and is the main variant responsible for stemness properties in these cells furthermore, its overexpression in fibroblast cells produces induced pluripotent stem (iPS) cells 9, 10, 11, 12. Up until now, several studies have shown that the expression of OCT4 gene can be regulated by microRNAs, and also some microRNA genes can be regulated by OCT4 protein. Greer Card et al. (2008) showed that miR-302 is transcriptionally activated by Oct4/Sox2 which binds to the promoter region of the miR-302 cluster in human ES cells 13. In 2009, Xu et al. demonstrated that miR-145 promoter is bound and repressed by OCT4 in ES cells and surprisingly, OCT4 3？-UTR can be targeted and down-regulated by miR-145 14. MicroRNAs are a group of non-coding RNAs (nc-RNAs), which are ～ 21 nucleotides long and were introduced for the first time by Ambros group