title: miR-4262 promotes the proliferation of human cutaneous malignant melanoma cells through KLF6-mediated EGFR inactivation and p21 upregulation.
abstract: Alterations in the levels and functions of microRNAs (miRs) have been associated with carcinogenesis. In this study, we investigated the role and underlying mechanism of miR-4262 in the proliferation of human cutaneous malignant melanoma (CMM) cells. The expression levels of miR-4262 were significantly upregulated in cancerous tissues compared with those in matched adjacent normal tissues from 110 CMM patients. miR-4262 was also regulated in five types of CMM cell lines, displaying an opposite expression pattern to that of Kruppel-like 6 (KLF6), a proven tumor suppressor in several cancers other than CMM. KLF6 overexpression sharply reduced A375 cell proliferation, suppressed the activation of epidermal growth factor receptor (EGFR) and increased p21 expression levels, while knockdown of KLF6 by siRNA transfection had an opposite effect. Furthermore, KLF6 was proven to be a direct target gene of miR-4262 by bioinformatic analysis and KLF6‑3'UTR luciferase reporter assay. Finally, our data on miR-4262 mimic and inhibitor transfection indicated that miR-4262 could markedly reduce the expression of KLF6 protein and had a stimulatory effect on A375 cell proliferation. Our findings indicate that KLF6 acts as a tumor suppressor in CMM cells and miR-4262 promotes the proliferation of CMM cells through KLF6-mediated EGFR inactivation and p21 upregulation.
authors: Department of Dermatology, The Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors: Dingwei
authors: D
authors: Zhang
authors: Department of Dermatology, The Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors: Zhangjun
authors: Z
authors: Li
authors: Department of Dermatology, The Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors: Yanfei
authors: Y
authors: Zhang
authors: Department of Dermatology, The Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors: Chen
authors: C
authors: Tu
authors: Department of Dermatology, The Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors: Jia
authors: J
authors: Huo
authors: Department of Dermatology, The Second Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
authors: Yan
authors: Y
authors: Liu
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C105465:KLF6 protein, human; D000075723:Kruppel-Like Factor 6; D051741:Kruppel-Like Transcription Factors; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C000612722:microRNA-4262 microRNA, human; C512478:EGFR protein, human; D066246:ErbB Receptors