Expression patterns of microRNA-218 and its potential functions by targeting CIP2A and BMI1 genes in melanoma.
Melanoma is the most aggressive skin cancer, and it is typically resistant or rapidly develops resistance to a variety of chemotherapeutic agents. microRNAs (miRNAs) play a part in the occurrence and development of malignant melanoma. In this study, we analyzed the miR-218 expression level in melanoma patients and cell lines and observed alterations in proliferation, cell cycle, migration, and invasion by increasing miR-218 expression in melanoma cell lines. We also performed bioinformatic analyses using TargetScan and miRanda and cloned both the wild-type and mutant versions of the human cancerous inhibitor of protein phosphatase 2A (CIP2A) and B lymphoma Mo-MLV insertion region 1 (BMI1) 3'-UTR fragments into the pmirGLO reporter vector. We then used the Dual-Luciferase assay system, quantitative real-time RT-PCR (qRT-PCR), and Western blot analysis to determine that miR-218 targeted the 3'-UTR of the oncogenes CIP2A and BMI1 and thus regulated the biological process of melanoma. We further demonstrated that CIP2A and BMI1 knockdown phenocopies miR-218 overexpression. In conclusion, our findings have shown that miR-218 is downregulated in melanoma. By targeting CIP2A and BMI1, miR-218 regulates the proliferation, migration, and invasion of the melanoma cell lines A375 and SK-MEL-2, indicating that miR-218 plays a pivotal role in melanoma development.
Department of Dermatology, The People's Hospital of Jiaozuo City, Jiaozuo, 454000, Henan, China.
Yanping
Y
Wei
Yuwen
Y
Du
Xiaonan
X
Chen
Ping
P
Li
Yuanyuan
Y
Wang
Wenqiao
W
Zang
Lindong
L
Zhao
Zhongdong
Z
Li
Guoqiang
G
Zhao
D020413:3' Untranslated Regions; D001324:Autoantigens / Q000235:genetics*; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008545:Melanoma / Q000235:genetics / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D063150:Polycomb Repressive Complex 1 / Q000235:genetics*
D020413:3' Untranslated Regions; D001324:Autoantigens; C069077:BMI1 protein, human; C500266:CIP2A protein, human; D047908:Intracellular Signaling Peptides and Proteins; C547471:MIRN218 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D063150:Polycomb Repressive Complex 1