miR-1246在疾病上的研究进展

doi:10.13560/j.cnki.biotech.bull.1985.2017.03.005

摘要/Abstract

摘要： miRNAs是一类具有转录调控功能的小分子非编码RNA,参与了组织代谢和细胞增殖、分化、凋亡及基因表达,在许多生理和病理过程中扮演着重要的角色。目前,研发有效的miRNA激活剂或抑制剂来挽救和诊断病理状态,已成为医学研究领域的新方向和切入点。最新发现的miR-1246受P53调控,并与产生疾病的分子机制息息相关。综述了miR-1246序列结构特点及分子作用机制,对近年来miR-1246在癌症、埃博拉病毒传染病、唐氏综合症等疾病上的应用潜能进行了总结,并对该领域今后的发展前景作了展望,旨为医学研究提供理论参考。

关键词: miR-1246, 癌症, 唐氏综合症, 埃博拉病毒感染, 疾病

Abstract: miRNAs are a class of small non-coding RNAs,involve in tissues metabolism,cells proliferation,differentiation,apoptosis and target genes expression,thus play an critical role in physiological and pathological processes. Nowadays,inventing effective miRNAs activators or inhibitors to treat and diagnose disease has become a new direction or entry point in the field of medical research. The newly discovered miR-1246 is regulated by P53,and is closely related to molecular mechanism of diseases. In this article,we summarize the miR-1246’s sequence structural features,molecular functional mechanism,review application potentials of miR-1246 in treating cancer,Ebola virus infection,and Down’s syndrome,and finally discuss its prospects,aiming at providing a theoretical reference for medical research.

Key words: miR-1246, cancer, Down's syndrome, Ebola virus infection, disease

胡煜, 王玲, 毕武, 谭林, 邢丹, 左福元. miR-1246在疾病上的研究进展[J]. 生物技术通报, 2017, 33(3): 29-36.

HU Yu, WANG Ling, BI Wu, TAN Lin, XING Dan, ZUO Fu-yuan. Research Progress of miR-1246 in Diseases[J]. Biotechnology Bulletin, 2017, 33(3): 29-36.

参考文献

[1] Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4, encodes small RNAs with antisense complementarity to lin-14[J]. Cell, 1993, 75（5）：843-854.
[2] Dooley AL, Winslow MM, Chiang DY, et al. Nuclear factor I/B is an oncogene in small cell lung cancer[J]. Genes & Development, 2011, 25（14）：1470-1475.
[3] Kosaka N, Iguchi H, Ochiya T, et al. Circulating microRNA in body fluid：a new potential biomarker for cancer diagnosis and prognosis[J]. Cancer Science, 2010, 101（10）：2087-2092.
[4] Pigati L, Yaddanapudi SCS, Iyengar R, et al. Selective release of microRNA species from normal and malignant mammary epithelial cells[J]. PLoS One, 2010, 5（10）：e13515.
[5] Suzuki HI, Yamagata K, Sugimoto K, et al. Modulation of microRNA processing by p53[J]. Nature, 2009, 460（7254）：529-533.
[6] Liao JM, Zhou X. New insights into p53 functions through its target microRNAs[J]. J Mol Cell Biol, 2014, 6（3）：206-213.
[7] Gregory RI, Chendrimada TP, Cooch N, et al. Human RISC couples microRNA biogenesis and posttranscriptional gene silencing[J]. Cell, 2005, 123（4）：631-640.
[8] Baek D, Villén J, Shin C, et al. The impact of microRNAs on protein output[J]. Nature, 2008, 455（7209）：64-71.
[9] Chen J, Yao D, Zhao S, et al. MiR-1246 promotes SiHa cervical cancer cell proliferation, invasion, and migration through suppression of its target gene thrombospondin 2[J]. Arch Gynecol Obstet, 2014, 4：725-732.
[10] Kim H, Watkinson J, Varadan V, et al. Multi-cancer computational analysis reveals invasion-associated variant of desmoplastic reaction involving INHBA, THBS2 and COL11A1[J]. American Geophysical Union, 2010, 3（4）：367-376.
[11] Doeberitz MVK, Rittmüller C, Hausen HZ, et al. Inhibition of tumorigenicity of cervical cancer cells in nude mice by HPV e6-e7 anti-sense RNA[J]. Int J Cancer NLM, 1992, 5：831-834.
[12] Bosch FX, Ribes J, Díaz M, et al. Primary liver cancer：worldwide incidence and trends[J]. Gastroenterology, 2004, 127（5 Suppl 1）：S5-S16.
[13] Sun Z, Meng C, Wang S, et al. MicroRNA-1246 enhances migration and invasion through CADM1 in hepatocellular carcinoma[J]. Molecular Oncology, 2014, 14（1）：1-11.
[14] Zhang Q, Cao LY, Cheng SJ, et al. P53-induced microRNA-1246 inhibits the cell growth of human hepatocellular carcinoma cells by targeting NFIB[J]. Oncol Rep, 2015, 33（3）：1335-1341.
[15] Bouyssou JMC, Manier S, et al. Regulation of microRNAs in cancer metastasis[J]. Biochim Biophys Acta, 2014, 2：255-265.
[16] Perry BC, Soltys D, Toledo AH, et al. Tumor necrosis factor-α in liver ischemia/reperfusion injury[J]. J Invest Surg, 2011, 24（4）：178-188.
[17] Leal JA, Lleonart ME. MicroRNAs and cancer stem cells：therapeutic approaches and future perspectives[J]. Cancer Lett, 2013, 338（1）：174-183.
[18] Huang W, Li H, Luo R, et al. The microRNA-1246 promotes metastasis in non-small cell lung cancer by targeting cytoplasmic polyadenylation element-binding protein 4[J]. Diagn Pathol, 2015, 10（1）：1-10.
[19] Kim G, An HJ, Lee MJ, et al. Hsa-miR-1246 and hsa-miR-1290 are associated with stemness and invasiveness of non-small cell lung cancer[J]. Lung Cancer, 2015, 91：15-22.
[20] Antonarakis SE, Lyle R, Dermitzakis ET, et al. Chromosome 21 and down syndrome：from genomics to pathophysiology[J]. Nat Rev Genet, 2004, 5（10）：725-738.
[21] Becker W, Sippl W. Activation, regulation, and inhibition of DYRK1A[J]. Febs Journal, 2011, 278（2）：246-256.
[22] Yang EJ, Ahn YS, Chung KC, et al. Protein kinase Dyrk1 activates cAMP response element-binding protein during neuronal differentiation in hippocampal progenitor cells[J]. J Biol Chem, 2001, 276（43）：39819-39824.
[23] Arron JR, Winslow MM, Polleri A, et al. NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21[J]. Nature, 2006, 441（7093）：595-600.
[24] Gwack Y, Sharma S, Nardone J, et al. A genome-wide drosophila RNAi screen identifies DYRK-family kinases as regulators of NFAT[J]. Nature, 2006, 441（441）：646-650.
[25] Woods Y, Rena GN, Barthel A, et al. The kinase DYRK1A phosphorylates the transcription factor FKHR at Ser329 in vitro, a novel in vivo phosphorylation site[J]. Biochemical Journal, 2001, 355（Pt 3）：597-607.
[26] Liao JM, Zhou X, Zhang Y, et al. MiR-1246：a new link of the p53 family with cancer and down syndrome[J]. Cell Cycle, 2012, 11（14）：2624-2630.
[27] Zhang Y, Liao JM, Zeng SX, et al. P53 downregulates down syndrome-associated DYRK1A through miR-1246[J]. Embo Reports, 2011, 12（8）：811-817.
[28] Colebunders R, Borchert M. Ebola haemorrhagic fever - a review[J]. Journal of Infection, 2000, 40（1）：16-20.
[29] Sheng MM, Zhong Y, et al. Hsa-miR-1246, hsa-miR-320a and hsa-miR-196b-5p inhibitors can reduce the cytotoxicity of ebola virus glycoprotein in vitro[J]. Sci China Life Sci, 2014, 10：959-972.
[30] Provencal M, Michaud M, Beaulieu E, et al. Tissue factor pathway inhibitor（TFPI）interferes with endothelial cell migration by inhibition of both the Erk pathway and focal adhesion proteins[J]. Thromb Haemost, 2008, 99（3）：576-585.
[31] Chen J, Zhang B, Pan C, et al. Effects of monocyte chem-otactic protein-3 on ICAM-1, VCAM-1, TF, and TFPI expression and apoptosis in human umbilical vein endothelial cells[J]. Nan Fang Yi Ke Da xue xue Bao, 2013, 33：86-92.
[32] Belkin AM, Smalheiser NR. Localization of cranin（dystroglycan）at sites of cell-matrix and cell-cell contact：recruitment to focal adhesions is dependent upon extracellular ligands[J]. Cell Adhesion & Communication, 1996, 4（4-5）：281-296.
[33] Brancaccio A. DAG1, no gene for RNA regulation[J]. Gene, 2012, 497（1）：79-82.
[34] Winckers K, Cate HT, Hackeng TM, et al. The role of tissue factor pathway inhibitor in atherosclerosis and arterial thrombosis[J]. Blood Reviews, 2013, 27（3）：119-132.
[35] He MX, He YW. CFLAR/c-FLIPL：a star in the autophagy, apoptosis and necroptosis alliance[J]. Autophagy, 2013, 9（5）：791-793.
[36] Javierre BM, Richardson B. A new epigenetic challenge：systemic lupus erythematosus[J]. Adv Exp Med Biol, 2011, 711：117-136.
[37] Liu A, La CA. Epigenetic dysregulation in systemic lupus erythematosus[J]. Autoimmunity, 2014, 47（4）：215-219.
[38] Deng Y, Tsao BP. Advances in lupus genetics and epigenetics[J]. Current Opinion in Rheumatology, 2014, 26（5）：482-492.
[39] Guo Y, Sawalha AH, Lu Q, et al. Epigenetics in the treatment of systemic lupus erythematosus：potential clinical application[J]. Clinical Immunology, 2014, 155（1）：79-90.
[40] Ming Z, Liu S, Luo S, et al. DNA methylation and mRNA and microRNA expression of SLE CD4+ T cells correlate with disease phenotype[J]. J Autoimmu, 2014, 54：127-136.
[41] Yébenes VGD, Bartolomé-Izquierdo N, Ramiro AR, et al. Regula-tion of B-cell development and function by microRNAs[J]. Proc Spie, 2013, 253（1）：25-39.
[42] Luo S, Yu L, Liang G, et al. The role of microRNA-1246 in the regulation of B cell activation and the pathogenesis of systemic lupus erythematosus[J]. Clinical Epigenetics, 2015, 7（1）：1-13.
[43] Nair N, Kumar S, Gongora E, et al. Circulating miRNA as novel markers for diastolic dysfunction[J]. Molecular & Cellular Biochemistry, 2013, 376（1-2）：33-40.
[44] Melissa PH, Noura I, Zhang XL, et al. Detection of microRNA expression in human peripheral blood microvesicles[J]. PLoS One, 2008, 3（11）：e3694.
[45] Baraniskin A, Maike A, Steffen GJ, et al. Circulating U2 small nuclear RNA fragments as a novel diagnostic biomarker for pancreatic and colorectal adenocarcinoma[J]. Int J Cancer NLM, 2013, 132（2）：E48-E57.
[46] Pigati L, Yaddanapudi SCS, Iyengar R, et al. Selective release of microRNA species from normal and malignant mammary epithelial Cells[J]. PLoS One, 2010, 5（10）：e13515.
[47] Xu LJ, Jiang T, Zhao W, et al. Parallel mRNA and microRNA profiling of HEV71-infected human neuroblastoma cells reveal the up-regulation of miR-1246 in association with DLG3 repression[J]. PLoS One, 2014, 9（4）：e95272-e95272.
[48] Zheng Y, Chen KL, Zheng XM, et al. Identification and bioinformatics analysis of microRNAs associated with stress and immune response in serum of heat-stressed and normal Holstein cows[J]. Cell Stress Chaperones, 2014, 6：973-981.
[49] Sarachana T, Dahiya N, Simhadri VL, et al. Small ncRNA expression-profiling of blood from hemophilia A patients identifies miR-1246 as a potential regulator of factor 8 gene[J]. PLoS One, 2015, 10（7）：1-14
[50] Wang S, Zeng Y, Zhou JM, et al. MicroRNA-1246 promotes growth and metastasis of colorectal cancer cells involving CCNG2 reduction[J]. Mol Med Rep, 2016, 13（1）：273-280.
[51] Shan D, Ding X, Song X, et al. Roles of microRNAs in cardiovascular diseases therapeutics[J]. Chemistry of Life, 2013, 33（4）：427-432.