Abstract
Aberrant expressions of microRNAs have been reported to be strongly associated with the progression and prognosis of various tumors, including oral squamous cell carcinoma (OSCC). Recent studies on miRNA expression profiling have suggested that microRNA‐16 (miR‐16) may be dysregulated in OSCC. However, the tumorigenic roles and mechanisms of miR‐16 in OSCC are still largely unknown. In this study, we demonstrated that miR‐16 was specifically downregulated in both OSCC patients and cancer cell lines. In addition, functional roles of miR‐16 in vitro suggested that the miR‐16 mimic inhibited cell proliferation and induced apoptosis, whereas miR‐16 inhibitor displayed the opposite effects. Luciferase reporter assay and correlation analysis showed that AKT3 and BCL2L2 were directly targeted by miR‐16 and were inversely expressed with miR‐16 in OSCC. Moreover, restoration of AKT3 and BCL2L2 expression could partially reverse the cell proliferation inhibition and apoptosis induction caused by miR‐16. In xenograft nude mice, miR‐16 mimics decreased the expression of AKT3 and BCL2L2 and reduced the tumors volumes and weights, whereas the miR‐16 inhibitor exhibited adverse effects in the derived xenografts. In conclusion, the findings suggested that miR‐16 functions as a tumor suppressor miRNA to inhibit cell proliferation and induce apoptosis in OSCC through decreasing the oncogenes AKT3 and BCL2L2 and that miR‐16 could be a potential therapeutic target for OSCC.
Highlights
Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer and the predominant histological type of oral cavity cancer (Chi, Day, & Neville, 2015)
We found that the apoptotic rate was significantly increased in microRNA‐ 16 (miR‐16) mimic transfected cells; the apoptotic rate was decreased after the expression of miR‐16 was inhibited in SCC‐25 and CAL‐27 cells (Figure 3)
The protein expressions of AKT3 and BCL2L2 were decreased in the miR‐16 mimic‐transfected group and increased in the miR‐16 inhibitor group (Figure 8d,e). These results suggested that miR‐16 functions as a tumor‐suppressor miRNA in OSCC through decreasing the oncogenes AKT3 and BCL2L2 (Figure 9)
Summary
Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer and the predominant histological type of oral cavity cancer (Chi, Day, & Neville, 2015). It broadly encompasses malignancies in the lips, tongue, pharynx, hard palate, and alveolar ridges with a high mortality rate and a poor prognosis. MicroRNAs (miRNAs) are endogenous single‐stranded noncoding RNAs approximately 22 nucleotides in length (Osada & Takahashi, 2007) It regulates protein‐coding gene expression by binding to the. The mechanisms underlying the role of miR‐16 together with its target genes in OSCC progression were explored in OSCC cells and animal models
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