MicroRNA miR-125b induces senescence in human melanoma cells

被引:43
作者
Glud, Martin [1 ,2 ,3 ]
Manfe, Valentina [1 ]
Biskup, Edyta [1 ]
Holst, Line [1 ]
Dirksen, Anne Marie Ahlburg [1 ]
Hastrup, Nina [4 ]
Nielsen, Finn C. [5 ,6 ]
Drzewiecki, Krzysztof T. [2 ,3 ,5 ]
Gniadecki, Robert [1 ,5 ]
机构
[1] Univ Copenhagen, Bispebjerg Hosp, Dept Dermatol, DK-2100 Copenhagen, Denmark
[2] Univ Copenhagen, Dept Plast Surg, DK-2100 Copenhagen, Denmark
[3] Univ Copenhagen, Burn Unit, DK-2100 Copenhagen, Denmark
[4] Univ Copenhagen, Dept Pathol, DK-2100 Copenhagen, Denmark
[5] Univ Copenhagen, Fac Hlth Sci, DK-2100 Copenhagen, Denmark
[6] Univ Copenhagen, Rigshospitalet, DK-2100 Copenhagen, Denmark
关键词
Akt3; apoptosis; melanoma cell line; microRNA; miR-125b; proliferation; senescence; EXPRESSION; AKT; NEVI;
D O I
10.1097/CMR.0b013e328345333b
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
MicroRNAs (miRNAs) are small noncoding RNA molecules involved in gene regulation. Aberrant expression of miRNA has been associated with the development or progression of several diseases, including cancer. In a previous study, we found that the expression of miRNA-125b (miR-125b) was two-fold lower in malignant melanoma producing lymph node micrometastases than in nonmetastasizing tumors. To get further insight into the functional role of miR-125b, we assessed whether its overexpression or silencing affects apoptosis, proliferation, or senescence in melanoma cell lines. We showed that overexpression of miR-125b induced typical senescent cell morphology, including increased cytoplasmatic/nucleus ratio and intensive cytoplasmatic beta-galactosidase expression. In contrast, inhibition of miR-125b resulted in 30-35% decreased levels of spontaneous apoptosis. We propose that downregulation of miR-125b in an early cutaneous malignant melanoma can contribute to the increased metastatic capability of this tumor. Melanoma Res 21:253-256 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
引用
收藏
页码:253 / 256
页数:4
相关论文
共 22 条
[1]   Growth dynamics and cyclin expression in cutaneous T-cell lymphoma cell lines [J].
Biskup, Edyta ;
Manfe, Valentina ;
Kamstrup, Maria ;
Gniadecki, Robert .
DERMATOLOGY REPORTS, 2010, 2 (01) :21-22
[2]   Akt and mutant V600EB-Raf cooperate to promote early melanoma development [J].
Cheung, Mitchefl ;
Sharma, Arati ;
Madhunapantula, SubbaRao V. ;
Robertson, Gavin P. .
CANCER RESEARCH, 2008, 68 (09) :3429-3439
[3]  
Dhawan P, 2002, CANCER RES, V62, P7335
[4]   Oncomirs - microRNAs with a role in cancer [J].
Esquela-Kerscher, A ;
Slack, FJ .
NATURE REVIEWS CANCER, 2006, 6 (04) :259-269
[5]   Downregulation of miR-125b in metastatic cutaneous malignant melanoma [J].
Glud, Martin ;
Rossing, Maria ;
Hother, Christoffer ;
Holst, Line ;
Hastrup, Nina ;
Nielsen, Finn C. ;
Gniadecki, Robert ;
Drzewiecki, Krzysztof T. .
MELANOMA RESEARCH, 2010, 20 (06) :479-484
[6]   MicroRNA Expression in Melanocytic Nevi: The Usefulness of Formalin-Fixed, Paraffin-Embedded Material for miRNA Microarray Profiling [J].
Glud, Martin ;
Klausen, Mikkel ;
Gniadecki, Robert ;
Rossing, Maria ;
Hastrup, Nina ;
Nielsen, Finn C. ;
Drzewiecki, Krzysztof T. .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2009, 129 (05) :1219-1224
[7]   Mammalian microRNAs predominantly act to decrease target mRNA levels [J].
Guo, Huili ;
Ingolia, Nicholas T. ;
Weissman, Jonathan S. ;
Bartel, David P. .
NATURE, 2010, 466 (7308) :835-U66
[8]   Melanoma cell autonomous growth: The Rb/E2F pathway [J].
Halaban, R .
CANCER AND METASTASIS REVIEWS, 1999, 18 (03) :333-343
[9]   IGF1 promotes resistance to apoptosis in melanoma cells through an increased expression of BCL2, BCL-X(L), and survivin [J].
Hilmi, Caroline ;
Larribere, Lionel ;
Giuliano, Sandy ;
Bille, Karine ;
Ortonne, Jean-Paul ;
Ballotti, Robert ;
Bertolotto, Corine .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2008, 128 (06) :1499-1505
[10]   Notch signalling in primary cutaneous CD30+lymphoproliferative disorders: a new therapeutic approach? [J].
Kamstrup, M. R. ;
Biskup, E. ;
Gniadecki, R. .
BRITISH JOURNAL OF DERMATOLOGY, 2010, 163 (04) :781-788