hsa-miR-543 Acts as a Tumor Suppressor by Targeting NMYC

摘要

Cancer is a complex human disease involving de-regulation of one or many developmental pathways. Aberrant activation of canonical Wnt signaling pathway, one of the most important developmental pathways, is a common cause of various carcinomas. Therefore, it is possible that potential cancer drugs can be developed by targeting the different nodal points of this signaling pathway. MYCN is a transcription factor of MYC family proto-onco gene. N-Myc over expression is known to be associated with various childhood tumors like neuroblastomas, medulloblastomas and prostate and lungs cancers in adults. MicroRNAs are short non-protein coding RNAs that bring about translational repression of the target gene by binding to its 3'UTR. Reports show that microRNAs play a significant role in carcinogenesis by acting as oncogenes or tumor suppressors. Oncogenic potential of hsa-miR-543 has been shown in prostate and cervical cancers, whereas, it tumor suppressive role has been reported in gliomas and colorectal cancers. Neuroblastoma patients show allelic loss of chromosome 14q, where miR-543 is located indicating the possibility of miR-543 playing an important role in neuroblastoma progression and prognosis. In the current study, we demonstrated that over-expression of miR-543 down-regulates the endogenous expression of N-Myc in HEK293FT cells. Also, it is shown to target FZD4, thereby, indirectly affecting the expression of other downstream genes of Wnt signaling including CTNNB1, TCF4 and LEF1. Therefore, our results suggest that miR-543 plays a significant role in suppressing the carcinomas resulted due to the over-expression of N-Myc and/or activation of Wnt pathway and may prove to be a potential target for novel cancer therapy.