Abstract
Bromodomain containing 7 (BRD7) was identified as a nuclear transcriptional regulatory factor. BRD7 functions as a tumor suppressor in multiple cancers, including nasopharyngeal carcinoma (NPC). In this study, we reported a novel mechanism of BRD7 in NPC progression. We demonstrated that the expression of miR-141 was remarkably increased in NPC tissues and was negatively correlated with the expression of BRD7 and the survival rate of NPC patients. Decreased expression levels of miR-141, including the primary, the precursor and the mature forms of miR-141, were found in BRD7-overexpressing HEK293, 5-8F and HNE1 cells compared the control cells, while there was no obvious effect on the expression levels of the two critical enzymes Drosha and Dicer. BRD7 can negatively regulate the promoter activity of miR-141, while no obvious binding site of BRD7 was found in the potential promoter region of miR-141. Moreover, ectopic expression of miR-141 can significantly promote cell proliferation and inhibit apoptosis in NPC, and rescuing the expression of miR-141 in BRD7-overexpressing NPC cells could partially reverse the tumor suppressive effect of BRD7 on cell proliferation and tumor growth in vitro and in vivo. Furthermore, the activation of the PTEN/AKT pathway mediated by the overexpression of BRD7 could be inhibited by rescuing the expression of miR-141, which accordingly results in the partial restoration of cell proliferation and tumor growth. Our findings demonstrate that the BRD7/miR-141/PTEN/AKT axis has critical roles in the progression of NPC and provide some promising targets for the diagnosis and treatment of NPC.
Highlights
It is essential for us to identify sensitive biomarkers and drug targets contributing to early diagnosis and improving treatment outcomes for Nasopharyngeal carcinoma (NPC) patients in the early stages
Most patients exhibited a significant decrease in the expression of the BRD7 protein and an increase in the level of miR-141 when compared with the normal control tissues (Figures 1a and b), and the expression level of miR-141 was negatively correlated with the protein level of BRD7 in NPC patients (Po0.001, Table 2)
These findings indicate that both BRD7 and miR-141 might be involved in NPC progression and that BRD7 might be a negative regulator of miR-141 in NPC
Summary
It is essential for us to identify sensitive biomarkers and drug targets contributing to early diagnosis and improving treatment outcomes for NPC patients in the early stages. Deregulation of miR-200 family members in cancers has been associated with the growth, apoptotic response and regulation of metastasis.[23,24,25] numerous studies have yielded conflicting results regarding the role of miR-141 in tumor progression of different cancer types.[26,27,28,29]. We hypothesized that miR-141 might be involved in BRD7-mediated cell proliferation and tumor formation in the progression of NPC
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