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BRD7 expression and c-Myc activation forms a double-negative feedback loop that controls the cell proliferation and tumor growth of nasopharyngeal carcinoma by targeting oncogenic miR-141
- Source :
- Journal of Experimental & Clinical Cancer Research, Vol 37, Iss 1, Pp 1-14 (2018)
- Publication Year :
- 2018
- Publisher :
- BMC, 2018.
-
Abstract
- Abstract Background miR-141 is up-regulated and plays crucial roles in nasopharyngeal carcinoma (NPC). However, the molecular mechanism underlying the dysregulation of miR-141 is still obscure. Methods Thus, the ChIP-PCR was performed to identify the c-Myc-binding sites in miR-141 and BRD7. qRT-PCR, western blot and immunohistochemistry assays were used to detect the expression of miR-141 and its up/down stream molecules. The rescue experiments on the c-Myc/miR-141 axis were performed in vitro and in vivo. Results Our results showed that the levels of mature miR-141, pre-miR-141 and pri-miR-141 were downregulated in c-Myc knockdown NPC cells. Meanwhile, c-Myc transactivates the expression of miR-141 by binding its promoter region. Moreover, BRD7 was identified as a co-factor of c-Myc to negatively regulate the activation of c-Myc/miR-141 axis, as well as a direct target of c-Myc. Moreover, restoration of miR-141 in c-Myc knockdown NPC cells notably rescued the effect of c-Myc on cell proliferation and tumor growth, as well as the blocking of PTEN/AKT pathway. Additionally, the expression of c-Myc was positively correlated with that of miR-141 and the clinical stages of NPC patients and negatively associated with the expression of BRD7. Our findings demonstrated that BRD7 expression and c-Myc activation forms a negative feedback loop to control the cell proliferation and tumor growth by targeting miR-141. Conclusions These observations provide new mechanistic insights into the dysregulation of miR-141 expression and a promising therapeutic option for NPC.
Details
- Language :
- English
- ISSN :
- 17569966
- Volume :
- 37
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Journal of Experimental & Clinical Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.9f78f0f80e9b43819e38235e3d6b5988
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s13046-018-0734-2