Proto-oncogenic miR-744 is upregulated by transcription factor c-Jun via a promoter activation mechanism
Metrics: PDF 697 views | HTML 918 views | ?
Zhou Sha1,*, Xiaoxia Zhu1,*, Na Li1, Yiyi Li1, Dianhe Li1
1Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
*These authors contributed equally to this work
Xiaoxia Zhu, email: email@example.com
Keywords: miR-744, c-Jun, nasopharyngeal carcinoma, non-small cell lung cancer, migration
Received: January 28, 2016 Accepted: August 08, 2016 Published: August 13, 2016
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.