期刊文献+

皮肤黑素瘤中MicroRNA-149-3p的表达及与GSK-3α和Mcl-1相关性分析

Expression and Significance of MicroRNA-149-3p in Cutaneous Melanoma and Correlation to the Expression of GSK-3α and Mcl-1
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摘要 目的研究miR-149-3p在皮肤黑素瘤组织中的表达情况及其与GSK-3α和Mcl-1的相关性,探讨p53-miR-149-3p-GSK3-α-Mcl-1通路在皮肤黑素瘤发生、发展中的作用。方法应用原位杂交法检测89例皮肤黑素瘤和19例痣细胞痣患者病变组织miR-149-3p表达,运用免疫组化法检测皮肤黑素瘤组织中GSK-3α和Mcl-1表达。结果 miR-149-3p在皮肤黑素瘤组织中阳性率为68.5%,在痣细胞痣组织中阳性率为26.3%,两者差异有统计学意义(P<0.05);皮肤黑素瘤组织中miR-149-3p与GSK-3α的表达、GSK-3α与Mcl-1的表达均呈明显负相关性(P<0.05)。结论 miR-149-3p在皮肤黑素瘤组织中高表达,提示其与黑素瘤的发生发展有密切关系。miR-149-3p与GSK-3α和Mcl-1的表达有明显的相关性,提示p53-miR-149-3p-GSK-3α-Mcl-1通路存在于人皮肤黑素瘤组织中,可能对黑素瘤细胞的凋亡有重要的影响,其中miR-149-3p作为一种黑素瘤的促癌基因,有望成为一种皮肤黑素瘤有效的生物学标记和治疗靶点。 Objective To investigate the expression of miR-149-3p in cutaneous melanoma, and the correlation of expression with GSK-3α and Mcl-1. To further explain and demonstrate the role of p53-dependent, miR-149-3p- GSK-3α - Mcl-1 pathway in occurrence and development of melanoma. Methods Applying in situ molecular hybridization technique for the detection of miR-149-3p expressions in tissue samples from 89 melanoma eases, 19 nevocellular nevus cases. Applying in immunohistochemical staining for the detection of GSK-3oL and Mcl- 1. Results The positive rates of miR-149-3p expression were 68.5% in 89 melanoma cases; the positive rates of miR-149-3p expression was 26.3% in 19 nevocellular nevus cases. The expression of miR-149-3p was inversely correlated to the expression of GSK-3α, and the expression of GSK-3α also was inversely correlated to the protein of Mcl-1 ( P 〈 0.05 ). Conclusion The over-expression of miR-149-3p is considered closely corre- lated with the occurrence and development of melanoma, can be used as a kind of biomarker, the relationships among miR-149-3p, GSK-3α and Mcl-lsuggests that the p53-miR-149-3p-GSK-3α-Mcl-1 pathway has impor- tant effect on the apoptosis of melanoma cells, miR-149-3p may be a useful biomarker of melanoma progression and a therapeutic target for melanoma treatment.
出处 《中国皮肤性病学杂志》 CAS 北大核心 2014年第7期677-680,共4页 The Chinese Journal of Dermatovenereology
基金 上海市卫生局资助项目(20114125)
关键词 恶性黑素瘤 miR-149—3p MCL-1 Melanoma miR-149-3p Mcl-1
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参考文献15

  • 1Garbe C, Leiter U. Melanoma epidemiology and trends[ ]]. Clin Der- matol, 2009, 27 ( 1 ) :3-9.
  • 2I-Iauschild A, Weichenthal M, Rass K, et al. Efficacy of low-dose in- terferon {alphat2a 18 versus 60 months of treatment in patients with primary melanoma of > = 1.5 mm tumor thickness: results of a ran- domized phase III DeCOG trial[ J ]. J Clin Oncol, 2010, 28 (5) : 841 - 846.
  • 3Hodi FS, O Day SJ, McDermott DF, et al. Improved survival with ipil- imumab in patients with metastatic melanoma [ J ]. N Engl .I Med, 2010, 363(8) :711-723.
  • 4Nana-Sinkam SP, Fabbri M, Croce CM. MicroRNAs in cancer: person- alizing diagnosis and therapy [ J. J Ann N Y Acad Sci, 2010, 12 (10) :25-33.
  • 5Spat'row LE, Soong R, Dawkins HJ, et al. p53 gene mutation and ex- pression in naevi and melanomas [ J ]. Melanoma Res, 1995,5 (2) :93- 100.
  • 6吴斌,彭春.突变型P53蛋白在皮肤黑素瘤中的检测及临床意义[J].中国皮肤性病学杂志,2012,26(9):779-781. 被引量:4
  • 7Gelsleichter L, Gown AM, Zarbo RJ, et al. p53 and mdm-2 expression in malignant melanoma: an immunocytochemical study of expression of p53, mdm-2, and markers of cell proliferation in primary versus meta- static tumors[J]. Mod Pathol, 1995, 8(5) :530-535.
  • 8Jin L, Hu WL, Jiang CC, et al. MicroRNA-149 * , a p53-responsive microRNA, functions as an oncogenic regulator in human melanoma [J]. Proc Natl Acad Sci USA, 2011, 108(38) :15840-15845.
  • 9Avery-Kiejda KA, Zhang XD, Adams LJ, et al. Small molecular weight variants of p53 are expressed in human melanoma cells and are induced by the DNA-damaging agent cisplatin[ J]. Clin Cancer Res, 2008, 14 (6) : 1659-1668.
  • 10Manrer U, Charvet C, Wagman AS, et al. Glycogen synthase kinase- 3 regulates mitochondrial outer membrane permeabilization and apopto- sis by destabilization of MCL-1 [ J ]. Mol Cell, 2006, 21 (6) :749-760.

二级参考文献10

  • 1赵松,段惠军,齐凤英,李英敏.bcl-2、p53在皮肤肿瘤中的表达及意义[J].肿瘤研究与临床,2005,17(3):161-163. 被引量:5
  • 2束木娟,林梅绥,花井淳.不同部位恶性黑色素瘤DNA倍体分析和PCNA、p53蛋白的表达及其意义[J].临床与实验病理学杂志,2005,21(4):462-465. 被引量:5
  • 3Levine A J, Momand J, Fincay CA. The p53 tumor suppressor gene [ J]. Nature, 1991,351 (6326) :453 -456.
  • 4Lai RS, Wang JS, Hsu HK, et al. Prognostic e- valuation of the expression of p53 and bcl-2 on coproteins in patients with surgically reseeted non-small cell lung cancer [ J ]. Jpn J Clinoncol, 2002, 32(10) : 393 -397.
  • 5Velculescu VE, E1-Deiry WS. Biological and clinical importance of the p53 tumor suppressor gene[ J]. Clinical chemistry, 1996, 42 (6 Pt 1): 858-868.
  • 6Bergman R, Shemer A, Levy R, et al. Immuno- histochemical study of p53 protein expression in Spitz nevus as compared with other melanoeytie lesions[J]. Am J Dennatopathol, 1995, 17 (6) : 547 - 560.
  • 7Miracco C, Santopietro R, Biagioli M, et al.Different patterns of cell proliferation and death and oncogene expression in cutaneous malignant melanoma[ J]. J Cutan pathol, 1998, 25 (5) : 244 -251.
  • 8Chen YW, Klimstra DS, Mongeau ME, et al. Loss of p53 and Ink4a/ Arf cooperate in a cell autonomous fashion to induce metastasis of hepa- tocellular carcinoma cells [ J]. Cancer Res, 2007, 67 ( 16 ) : 7589 - 7596.
  • 9Reddy VB, Gattuso P, Aranha G, et al. Cell prolifaration markers in predicting melanoma metastsses in malignant melanoma [ J ]. J Cutan Pathol, 1995, 22(3) : 248 -251.
  • 10阎乎玲,刘芯,贾静,颜虹.p73和p53基因在皮肤鳞状细胞癌中的表达[J].中国皮肤性病学杂志,2009(10):618-620. 被引量:2

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