The p300/YY1/miR-500a-5p/HDAC2 signalling axis regulates cell proliferation in human colorectal cancer.

The biological role of miR-500a-5p has not yet been reported in the context of colorectal cancer (CRC). Here, we show that miR-500a-5p expression is decreased in CRC tissues compared with adjacent normal tissues. Low miR-500a-5p expression is associated with malignant progression. Moreover, transfection of CRC cells with miR-500a-5p induces G0/G1 ...
cell cycle arrest and inhibits their growth and migration. Mechanistically, miR-500a-5p directly targets HDAC2 and inhibits HDAC2-mediated proliferation in CRC in nude mice. Furthermore, YY1 binds to the promoter of miR-500a-5p and negatively regulates its transcription. Restoration of miR-500a-5p expression is up-regulated via the p300/YY1/HDAC2 complex. Besides, therapeutic delivery of miR-500a-5p significantly suppresses tumour development in a xenograft tumour model and a HDAC2 inhibitor FK228-treated CRC model. Our studies demonstrate that miR-500a-5p functions as a tumour suppressor in CRC by targeting the p300/YY1/HDAC2 axis, which contributes to the development of and provides new potential candidates for CRC therapy.
Mesh Terms:
Animals, Apoptosis, Cell Line, Cell Line, Tumor, Cell Proliferation, Colorectal Neoplasms, E1A-Associated p300 Protein, Female, Gene Expression Regulation, Neoplastic, HCT116 Cells, Histone Deacetylase 2, Humans, In Situ Nick-End Labeling, Mice, Mice, Inbred BALB C, Mice, Nude, MicroRNAs, Signal Transduction, YY1 Transcription Factor
Nat Commun
Date: Dec. 08, 2018
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