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.
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Contributors QG and PY participated in study design in vitro experiments. HW and GL participated in study design, in vitro experiments, and drafting of the manuscript.
Competing interests None declared.
Patient consent Obtained.
Ethics approval The use of patient samples was approved by the Institutional Review Board of Huazhong University of Science and Technology (Wuhan, China).
Provenance and peer review Not commissioned; externally peer reviewed.
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