Loss of MiR-664 Expression Enhances Cutaneous Malignant Melanoma Proliferation by Upregulating PLP2.
Proteolipid protein 2 (PLP2) has been shown to be upregulated in several cancers, including breast cancer, hepatocellular carcinoma, osteosarcoma, and melanoma. PLP2 specifically binds to phosphatidylinositol 3 kinase to activate the protein kinase B pathway to enhance cell proliferation, adhesion, and invasion in melanoma cells. Therefore, we speculated that PLP2 exhibits oncogenic potential. However, the regulatory mechanisms of PLP2 in cancer cells remain unclear.Herein, we found that microRNA (miR)-664 expression was significantly downregulated in cutaneous malignant melanoma (CMM) cells and tissues compared with normal human melanocytes and benign melanocytic naevi. MiR-664 expression level was significantly correlated with patient survival. Ectopic expression of miR-664 reduced CMM cell proliferation and anchorage-independent growth, whereas the inhibition of miR-664 induced these effects. Furthermore, inhibition of miR-664 in CMM cells resulted in modulation of their entry into the G1/S transitional phase, which was caused by downregulation of the cyclin-dependent kinase inhibitor P21 and upregulation of the cell-cycle regulator cyclin D1. Moreover, we demonstrated that miR-664 downregulated PLP2 expression by directly targeting the PLP2 untranslated region.Taken together, our results suggest that miR-664 may play an important role in suppressing proliferation of CMM cells and present a novel mechanism of miR-mediated direct suppression of PLP2 expression in cancer cells.
From the Department of Radiation Medicine (ZD, LZ, CO, YW, MZ), School of Public Health and Tropic Medicine, Southern Medical University,Guangzhou,Guangdong,China; Department of Hepatobiliopancreatic Surgery (SJ), Sun Yat-sen Memorial Hospital, Sun Yat-sen University Guangzhou,Guangdong,China Department of Dermatology (XP), Nanfang Hospital, Southern Medical University,Guangzhou,Guangdong,China; Guangzhou Twelfth Hospital (YL, JW); and Guangzhou Biocare Cancer Institute (WZ), Guangzhou, Guangdong, China.
Zhenhua
Z
Ding
Sun
S
Jian
Xuebiao
X
Peng
Yimin
Y
Liu
Jianyu
J
Wang
Li
L
Zheng
Chengshan
C
Ou
Yinghui
Y
Wang
Weixia
W
Zeng
Meijuan
M
Zhou
D000818:Animals; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D015870:Gene Expression; D006801:Humans; D062792:MARVEL Domain-Containing Proteins / Q000235:genetics*; D008545:Melanoma / Q000235:genetics / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D011510:Proteolipids / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D012878:Skin Neoplasms; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D000096142:Cutaneous Malignant Melanoma
D062792:MARVEL Domain-Containing Proteins; C000590115:MIRN664 microRNA, human; D035683:MicroRNAs; C094765:PLP2 protein, human; D011510:Proteolipids; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt