Among the malignant tumors of the human central nervous system, gliomas have the highest incidence and recurrence rate. Therefore, exploration of the molecular mechanism that underlies the development and progression of gliomas is of great clinical significance. Many studies have demonstrated that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play important roles in the development and progression of tumors. In the present study, both an RNAhybrid analysis and a dual-luciferase reporter gene assay confirmed that microRNA-15b (miR-15b) binding sites were present in the sequence of HOX transcript antisense RNA (HOTAIR). The present study further demonstrated that miR-15b, HOTAIR, and p53 formed a mutually regulated loop. MiR-15b upregulated the expression of p53 but inhibited the expression of HOTAIR. In addition, miR-15b was able to regulate the expression of HOTAIR through p53. P53 promoted miR-15b expression but inhibited HOTAIR expression. Furthermore, the examination of cell proliferation, apoptosis, and invasion revealed that both miR-15b and p53 inhibited the proliferation and invasion, but promoted the apoptosis, of glioma cells. In contrast, HOTAIR exerted effects that were the opposite of those exerted by miR-15b and p53 on glioma cells. The upregulation of HOTAIR suppressed the inhibitory effects of miR-15b and p53 on cell proliferation and invasion as well as the promoting effect of miR-15b and p53 on apoptosis. Therefore, it can be concluded that miR-15b, HOTAIR, and p53 constitute a regulatory loop that is capable of regulating the growth of glioma cells. This finding provides a new target for the treatment of gliomas.
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http://dx.doi.org/10.1002/jcb.26591 | DOI Listing |
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