title: Proto-oncogenic miR-744 is upregulated by transcription factor c-Jun via a promoter activation mechanism.
abstract: Upregulation of miR-744 is associated with poor prognosis in many types of cancer patients, but it is still unclear how miR-744 becomes elevated in these tumors. In this study, we found that ectopic c-Jun elevated miR-744 expression, whereas c-Jun attenuation reduced miR-744 expression. Chromatin immunoprecipitation assay confirmed the direct binding of c-Jun to the promoter of miR-744. The binding site of -343 to -349 bp within the most potential promoter like sequence of miR-744 was further validated by luciferase reporter gene assays. C-Jun-induced miR-744 upregulation could significantly promote migration and invasion of nasopharyngeal carcinoma cells and non-small cell lung cancer (NSCLC) cells, hence ectopic c-Jun was sufficient to rescue the migratory and invasive ability of these cells when miR-744 was knockdown. Additionally, a positive correlation between the expression levels of miR-744 and c-Jun was revealed in NSCLC samples with high (top 10%) level of miR-744 expression from the TCGA dataset. Taken together, our results demonstrated for the first time the regulatory mechanism of miR-744 transcription by c-Jun, providing a potential mechanism underlying the upregulation of miR-744 in cancers.
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Sha
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
authors.forename: Dianhe
authors.initials: D
authors.lastname: Li
mesh_terms: D063646:Carcinogenesis; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D009669:Nose Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: C569733:MIRN744 microRNA, human; D035683:MicroRNAs; D016755:Proto-Oncogene Proteins c-jun; D034741:RNA, Small Interfering
keywords: c-Jun; miR-744; migration; nasopharyngeal carcinoma; non-small cell lung cancer