AUTHOR=Yoshioka Hiroki , Ramakrishnan Sai Shankar , Shim Junbo , Suzuki Akiko , Iwata Junichi 

TITLE=Excessive All-Trans Retinoic Acid Inhibits Cell Proliferation Through Upregulated MicroRNA-4680-3p in Cultured Human Palate Cells

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.618876

DOI=10.3389/fcell.2021.618876

ISSN=2296-634X

ABSTRACT=<p>Cleft palate is the second most common congenital birth defect, and both environmental and genetic factors are involved in the etiology of the disease. However, it remains largely unknown how environmental factors affect palate development. Our previous studies show that several microRNAs (miRs) suppress the expression of genes involved in cleft palate. Here we show that <italic>miR-4680-3p</italic> plays a crucial role in cleft palate pathogenesis. We found that <italic>all-trans</italic> retinoic acid (<italic>at</italic>RA) specifically induces <italic>miR-4680-3p</italic> in cultured human embryonic palatal mesenchymal (HEPM) cells. Overexpression of <italic>miR-4680-3p</italic> inhibited cell proliferation in a dose-dependent manner through the suppression of expression of <italic>ERBB2</italic> and <italic>JADE1</italic>, which are known cleft palate-related genes. Importantly, a <italic>miR-4680-3p</italic>-specific inhibitor normalized cell proliferation and altered expression of <italic>ERBB2</italic> and <italic>JADE1</italic> in cells treated with <italic>at</italic>RA. Taken together, our results suggest that upregulation of <italic>miR-4680-3p</italic> induced by <italic>at</italic>RA may cause cleft palate through suppression of <italic>ERBB2</italic> and <italic>JADE1</italic>. Thus, miRs may be potential targets for the prevention and diagnosis of cleft palate.</p>