Abstract
A close relation between microRNA-151a-3p (miR-151a-3p) and nasopharyngeal carcinoma (NPC) has been reported, however, the molecular mechanism is still unclear. The aim of the present study was to explore the mechanism in the promotion of miR-151a-3p to NPC progression. The levels of miR-151-3p in several NPC cell lines were detected in order to screen an experimental cell line. MiR-151a-3p mimic and inhibitor were constructed and transfected into 5-8F cells and cell proliferation were detected by Cell Counting Kit-8 (CCK-8). The apoptosis rate, cell migration and invasion were determined by flow cytometry, wound healing and Transwell assays. The predicted target was further verified by luciferase reporter assay. Real-time quantification-PCR and Western blot were carried out for mRNA and protein level analysis. Tumor protein p53 was co-transfected to verify the functions of miR-151a-3p. The miR-151a-3p level in NPC tissues was much higher than that in adjacent tissues. After transfecting cells with miR-151a-3p mimic, the cell proliferation and patients’ survival rate were much increased, and this was accompanied by the increase in B-cell lymphoma 2 (Bcl-2) and decreases in Bax and cleaved caspase-3 (P<0.01). Moreover, the migration rate and number of invaded cells were also remarkably increased, however, the miR-151a-3p inhibitor had opposite effects on the 5-8F cells. Noticeably, p53 was revealed as a potential target of miR-151a-3p. Co-transfection of P53 could partially reverse the promotive effects of miR-151a-3p on NPC cell progression. Our data indicated that blocking p53 expression and mediated signal pathways contribute to the positive effects of miR-151a-3p on NPC cell proliferation, migration and invasion.
Highlights
Nasopharyngeal carcinoma (NPC), which is a nasopharyngeal mucosa cancer characterized by high invasiveness and metastasis, has a high incidence rate in endemic regions in southern China and Southeast Asia [1,2]
The level of miR-151a-3p was up-regulated in different NPC cell lines, especially in 5-8F cells
We detected the levels of several apoptosis-correlated proteins including the levels of B-cell lymphoma 2 (Bcl-2), Bax and cleaved caspase-3 (Figure 2D,E), and found that the up-regulated level of miR-151a-3p was accompanied by significantly down-regulated levels of pro-apoptotic protein (Bax and cleaved caspase-3), and the level of Bax protein was sharply up-regulated (P
Summary
Nasopharyngeal carcinoma (NPC), which is a nasopharyngeal mucosa cancer characterized by high invasiveness and metastasis, has a high incidence rate in endemic regions in southern China and Southeast Asia [1,2]. Radiotherapy is seen as the only effective method for treating NPC. Though radiotherapy in combination with radiotherapy has improved the survival rate of NPC patients, highly malignant recurrence and distance metastasis and local tissue invasion of NPC cells severely limited the efficacy of radiotherapy in NPC treatment [3]. In the past 20 years, the radiotherapy technique and radiotherapy in combination with chemotherapy have been well-developed to improve the 5-year overall survival rate to higher than 84.7–87.4% [4,5], but the overall survival for advanced NPC patients is still unsatisfactory [6]. Finding more effective strategies for treating NPC are still highly necessary
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