Novel inhibitory function of miR‐125b in melanogenesis

Kim, Kyu-Han; Bin, Bum-Ho; Kim, Juewon; Dong, Son Eui; Park, Phil June; Choi, Hyunjung; Kim, Beom Joon; Yu, Seok Jong; Kang, Hyojin; Kang, Hak Hee; Cho, Eun‐Gyung; Lee, Tae Ryong

doi:10.1111/pcmr.12179

Cited by 39 publications

(45 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Wu et al, (2014) also discovered that miRNAs might play an essential role in black and white follicle formation in goats, with miR 211 and miR-10 being significantly expressed in black hair follicles. Additionally, studies that investigated the over-expression of miR-25 in cultured melanocytes in Alpacas (Zhu et al 2010), the silencing of miR-429 in fish (Yan et al 2013) and that expression of miR-125b is inversely related to pigment levels and targets TYR and DCT (Kim et al 2014) have established the capacity for miRNAs to target candidate genes involved in melanogenesis. However, little is known about the presence of components of the miRNA machinery affecting melanogenesis in plumage pigmentation.…”

Section: Introductionmentioning

confidence: 98%

Identification and profiling of microRNAs associated with white and black plumage pigmentation in the white and black feather bulbs of ducks by RNA sequencing

et al. 2015

View full text Add to dashboard Cite

MicroRNAs (miRNAs) play important roles in many biological processes by regulating gene expression at the post-transcriptional level. However, the mechanism by which specific miRNAs may regulate plumage pigmentation has remained largely elusive. In this study, we sequenced miRNAs using Solexa sequencing and then performed a detailed analysis of their expression profiles between the black and white feather bulbs of ducks from Cui Hei, Kaiya, Liancheng pure breeds and a Kaiya-Liancheng F2 population. mirdeep2 software identified 121 conserved and eight novel miRNAs. Five differentially expressed miRNAs between the two tissues types were also identified by degseq software. Notably, miR-204 was predominantly expressed in black feather bulbs. To further validate the sequencing data, we applied stem-loop quantitative PCR of ten known miRNAs based on the identified sequences. Furthermore, in exploring the temporal expression pattern of miR-204, we performed profiling in nine duck tissues. The targets of these miRNAs were predicted using a PITA algorithm and were later grouped based on Gene Ontology and KEGG pathway analysis using the DAVID website. The melanogenesis pathway was among the identified signalling pathways, implying key roles of these miRNAs in plumage pigmentation. Expression analysis of the target genes in the melanogenesis pathways was also performed. This study provides the foundation for subsequent studies on the prospective practical role for such miRNAs in post-transcriptional gene regulation linked to plumage pigmentation.

show abstract

Section: Introductionmentioning

confidence: 98%

Identification and profiling of microRNAs associated with white and black plumage pigmentation in the white and black feather bulbs of ducks by RNA sequencing

et al. 2015

View full text Add to dashboard Cite

show abstract

“…4) miR-125b, whose expression is inversely related to pigment levels, is identified as a potent regulator of steady-state melanogenesis. 5) In a previous study, we created miR-137 overexpressing transgenic mice by microinjecting of miR-137 expression vector into mice zygotes, hence resulting in gray mice phenotype and found that the expression of miR-137 in gray mice skin was significantly higher than normal C57BL/6J black mice skin. 6) However, to date, the functional role of miR-137 in coat color regulation is still not well understood.…”

mentioning

confidence: 98%

MiR-137 affects melanin synthesis in mouse melanocyte by repressing the expression ofc-KitandTyrp2inSCF/c-Kitsignaling pathway

Jiang

Dong

2016

Bioscience, Biotechnology, and Biochemistry

View full text Add to dashboard Cite

Previously, we created miR-137 overexpressing transgenic mice that produced lighten color phenotypes including gray mice phenotype. However, the miR-137 functional role in coat color regulation is still not well understood. In this study, the quantity of melanin granule and the relative expression of TYRP2 in gray miR-137 overexpression transgenic mouse skin were significantly lower than that in C57BL/6J black mouse skin. The mRNA and protein expression level of c-Kit and c-Kit downstream gene Tyrp2 in miR-137 expression plasmid-transfected melanocytes were significantly down-regulated comparing with that of the control melanocytes. In melanocytes, miR-137 overexpression could decrease the enhanced expression of c-Kit and Tyrp2 and the increased melanin production caused by UV treatment. The target relationship of miR-137 and c-Kit was identified by luciferase assay. The results suggest that miR-137 could inhibit melanogenesis in mouse skin melanocytes by repressing the expression of c-Kit and Tyrp2 in SCF/c-Kit signaling pathway.

show abstract

“…MiR-125b expression is decreased in the primary cutaneous MM producing sentinel node metastasis comparing to the T-stage-matched non-metastasizing tumours [26]. This has later been confirmed by other groups [27,28]. Mir-125b is a known oncomir and has been implicated in the pathogenesis of leukemias and B-cell lymphomas, breast cancer, squamous cell carcinoma, urothelial carcinoma, prostate carcinoma and colon cancer [29-35].…”

Section: Introductionmentioning

confidence: 86%

“…Mir-125b is a known oncomir and has been implicated in the pathogenesis of leukemias and B-cell lymphomas, breast cancer, squamous cell carcinoma, urothelial carcinoma, prostate carcinoma and colon cancer [29-35]. In MM it has been shown to be related to the pigmentation level [27]. Kappelmann et al showed that treatment of MM cells with pre-mir-125b resulted in a strong suppression of cellular proliferation [28].…”

Section: Introductionmentioning

confidence: 99%

miR-125b induces cellular senescence in malignant melanoma

et al. 2014

View full text Add to dashboard Cite

BackgroundMicro RNAs (miRs) have emerged as key regulators during oncogenesis. They have been found to regulate cell proliferation, differentiation, and apoptosis. Mir-125b has been identified as an oncomir in various forms of tumours, but we have previously proposed that miR-125b is a suppressor of lymph node metastasis in cutaneous malignant melanoma. Our goal was therefore to further examine this theory.MethodsWe used in-situ-hybridization to visualise miR-125b expression in primary tumours and in lymph node metastasis. Then using a miRVector plasmid containing a miR-125b-1 insert we transfected melanoma cell line Mel-Juso and then investigated the effect of the presence of a stable overexpression of miR-125b on growth by western blotting, flow cytometry and β-galactosidase staining. The tumourogenicity of the transfected cells was tested using a murine model and the tumours were further examined with in-situ-hybridization.ResultsIn primary human tumours and in lymph node metastases increased expression of miR-125b was found in single, large tumour cells with abundant cytoplasm. A stable overexpression of miR-125b in human melanoma cell line Mel-Juso resulted in a G0/G1 cell cycle block and emergence of large cells expressing senescence markers: senescence-associated beta-galactosidase, p21, p27 and p53. Mel-Juso cells overexpressing miR-125b were tumourigenic in mice, but the tumours exhibited higher level of cell senescence and decreased expression of proliferation markers, cyclin D1 and Ki67 than the control tumours.ConclusionsOur results confirm the theory that miR-125b functions as a tumour supressor in cutaneous malignant melanoma by regulating cellular senescence, which is one of the central mechanisms protecting against the development and progression of malignant melanoma.

show abstract

Novel inhibitory function of miR‐125b in melanogenesis

Cited by 39 publications

References 19 publications

Identification and profiling of microRNAs associated with white and black plumage pigmentation in the white and black feather bulbs of ducks by RNA sequencing

Identification and profiling of microRNAs associated with white and black plumage pigmentation in the white and black feather bulbs of ducks by RNA sequencing

MiR-137 affects melanin synthesis in mouse melanocyte by repressing the expression ofc-KitandTyrp2inSCF/c-Kitsignaling pathway

miR-125b induces cellular senescence in malignant melanoma

Contact Info

Product

Resources

About