@article {Wang82, author = {Haihao Wang and Qiannan Guo and Peiwen Yang and Guoxian Long}, title = {Restoration of microRNA-212 causes a G0/G1 cell cycle arrest and apoptosis in adult T-cell leukemia/lymphoma cells by repressing CCND3 expression}, volume = {65}, number = {1}, pages = {82--87}, year = {2017}, doi = {10.1136/jim-2016-000233}, publisher = {BMJ Publishing Group Limited}, abstract = {Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive T-cell malignancy. This study was designed to explore the expression and functional significance of microRNA (miR)-212 in ATL. The expression of miR-212 in human ATL tissues and cell lines were investigated. Gain-of-function experiments were carried out to determine the roles of miR-212 in cell proliferation, tumorigenesis, cell cycle progression, and apoptosis. We also identified and functionally characterized the target genes of miR-212 in ATL cells. Compared with normal lymph node biopsies, lymphoma samples from ATL patients displayed underexpression of miR-212 (p=0.0032). Consistently, miR-212 was downregulated in human ATL cell lines, compared with normal T lymphocytes. Restoration of miR-212 significantly (p\<0.05) inhibited ATL cell proliferation and tumorigenesis in mice. Overexpression of miR-212 led to an accumulation of G0/G1-phase cells and a concomitant reduction of S-phase cells. Moreover, enforced expression of miR-212-induced significant apoptosis in ATL cells. CCND3, which encodes a cell cycle regulator cyclin D3, was identified as a direct target of miR-212 in ATL cells. Rescue experiments with a miR-212-resistant variant of CCND3 demonstrated that overexpression of CCND3 restored cell-cycle progression and attenuated apoptotic response in miR-212-overexpressing ATL cells. Taken together, miR-212 exerts growth-suppressive effects in ATL cells largely by targeting CCND3 and may have therapeutic potential in ATL.}, issn = {1081-5589}, URL = {http://hw-f5-jim.highwire.org/content/65/1/82}, eprint = {http://hw-f5-jim.highwire.org/content/65/1/82.full.pdf}, journal = {Journal of Investigative Medicine} }