Tian Fangzhen, Wei Hongtu, Tian Hua, Qiu Ying, Xu Jian
Department of Dermatology, Jining No. 1 People's Hospital, Jining, Shandong 272000, P.R. China.
Department of Orthopedics, Jining No. 1 People's Hospital, Jining, Shandong 272000, P.R. China.
Oncol Lett. 2016 Apr;11(4):2741-2746. doi: 10.3892/ol.2016.4321. Epub 2016 Mar 9.
MicroRNA-33a (miR-33a) was previously identified as a lipid regulator that controls the cellular balance between cholesterol and fatty acid metabolism. However, its role in tumor progression is largely unknown. The present study identified that miR-33a acts as a tumor suppressor in melanoma cells. The present study revealed that miR-33a was downregulated in melanoma cells compared with melanocytes. Overexpression of miR-33a suppressed the colony formation of human melanoma SK-MEL-1 and WM-115 cells. Furthermore, a bromodeoxyuridine incorporation assay and anaphase analysis revealed that miR-33a inhibits melanoma cell proliferation. miR-33a overexpression inhibited p27 phosphorylation and upregulated p27 expression. Additionally, the present study demonstrated that PCTAIRE1 was a direct target of miR-33a; miR-33a overexpression suppressed the luciferase activity of a reporter construct containing a 3'-untranslated region of PCTAIRE1 and downregulated PCTAIRE1 in melanoma cells. An overexpression of PCTAIRE1 reversed the miR-33a-induced p27 accumulation and tumor suppressive effects. In summary, the present findings offer novel mechanistic insights into miR-33a and its downstream target in melanoma cells.
微小RNA-33a（miR-33a）先前被鉴定为一种脂质调节剂，可控制胆固醇与脂肪酸代谢之间的细胞平衡。然而，其在肿瘤进展中的作用在很大程度上尚不清楚。本研究发现miR-33a在黑色素瘤细胞中发挥肿瘤抑制作用。本研究表明，与黑色素细胞相比，miR-33a在黑色素瘤细胞中表达下调。miR-33a的过表达抑制了人黑色素瘤SK-MEL-1和WM-115细胞的集落形成。此外，溴脱氧尿苷掺入试验和后期分析表明，miR-33a抑制黑色素瘤细胞增殖。miR-33a的过表达抑制了p27磷酸化并上调了p27表达。此外，本研究证明PCTAIRE1是miR-33a的直接靶点；miR-33a的过表达抑制了含有PCTAIRE1 3'-非翻译区的报告基因构建体的荧光素酶活性，并下调了黑色素瘤细胞中PCTAIRE1的表达。PCTAIRE1的过表达逆转了miR-33a诱导的p27积累和肿瘤抑制作用。总之，本研究结果为miR-33a及其在黑色素瘤细胞中的下游靶点提供了新的机制见解。
