MiR-135 post-transcriptionally regulates FOXO1 expression and promotes cell proliferation in human malignant melanoma cells.
Malignant melanoma is the deadliest form of all skin cancers. Recently, microRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by targeted repression of transcription and translation and play essential roles during cancer development. Our study showed that miR-135a is upregulated in malignant melanoma tissues and cell lines by using Real-time PCR assay. Enforced expression of miR-135a in malignant melanoma cells promotes cell proliferation, tumorigenicity, and cell cycle progression, whereas inhibition of miR-135a reverses the function. Additionally, we demonstrated FOXO1 is a direct target of miR-135a and transcriptionally down-regulated by miR-135a. Ectopic expression of miR-135a led to downregulation of the FOXO1 protein, resulting in upregulation of Cyclin D1, and downregulation of P21(Cip1) and P27(Kip1) through AKT pathway. Our findings suggested that miR-135a represents a potential onco-miRNA and plays an important role in malignant melanoma progression by suppressing FOXO1 expression.
Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an, Shaanxi, China.
Jian-Wen
JW
Ren
Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an, Shaanxi, China.
Zhang-Jun
ZJ
Li
Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an, Shaanxi, China.
Chen
C
Tu
D015153:Blotting, Western; D049109:Cell Proliferation; D005434:Flow Cytometry; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation
C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C544965:MIRN135 microRNA, human; D035683:MicroRNAs
FOXO1; malignant melanoma; miR-135a