Hsa-miR-106b-5p Negatively Regulates LEF1

Abstract

Aberrant expression of the genes involved in Wnt signaling pathway, one of the most important developing pathways, is observed in many malignancies. Reports show that Wnt/β-catenin activation is critical for cancer development, angiogenesis, migration, and invasion. LEF1 belongs to the T cell Factor (TCF)/LEF family of transcription factors and plays the role of nuclear effector in the Wnt/β-catenin signaling pathway. LEF1 has central role as a transcription factor in the Wnt/β-catenin signaling pathway which makes it an ideal target for therapeutic treatment in dealing with cancer proliferation. It can act as an oncogene or a tumor suppressor in cellular context dependent manner. miRNAs are aberrantly expressed in cancers and can act as tumor suppressors or oncomirs depending upon the type of carcinomas. Studies show that miRNAs can be used as novel agents for targeted cancer therapy. miR-106b, which belong to miR-17-92 paralog cluster, is reported to be overexpressed in multiple tumor types including medulloblastomas, breast, colon, kidney, gastric, lung cancer and HCC. In this study we have demonstrated that over-expression of miR-106b-5p down-regulates the endogenous expression of LEF1 in HEK293FT cells, thereby affecting the expression of N-Myc, downstream gene of Wnt signaling. Therefore, our results suggest that miR-106b-5p plays a significant role in suppressing the carcinomas resulted due to the over-expression of LEF1 and/or activation of Wnt pathway and may prove to be a potential target for novel cancer therapy. It may helpful in developing therapeutic strategies for cancer treatments.