双向负反馈环路lin28-let-7与肿瘤

摘要/Abstract

摘要：let-7家族是重要的肿瘤抑制因子，在干细胞分化和肿瘤抑制中起重要作用。RNA结合蛋白lin28是重要的干细胞因子，能维持细胞干性，促进细胞恶性转化。lin28可与let-7前体结合，阻断let-7成熟；而let-7可结合至lin28 mRNA的3′非翻译区（UTR），抑制lin28表达。lin28-let-7形成一个双向负反馈环路，参与干细胞分化、肿瘤发生、侵袭转移、耐药复发等生物过程，可作为肿瘤治疗新靶点。

关键词:肿瘤,微RNAs,RNA结合蛋白质类,肿瘤干细胞

Abstract:The microRNA let-7 family, functioning as a tumor suppressor, has emerged as a regulator of stem cell differentiation and tumor repression. The RNA-binding protein lin28 is a stem cell pluripotency factor, which contributes to the maintenance of stem cell characteristics and promoting cell malignant transformation. lin28 can block the maturity of let-7 by combining with the precursors of let-7 family miRNAs, which is itself able to repress lin28 by binding to the 3′-UTR of lin28 transcripts, thus forming a feedback loop. The doublenegative feedback loop comprising lin28 and let-7 is involved in several biological processes such as differentiation of stem cell, tumorigenesis, invasion and metastasis, drug resistance and relapse, which could be a potential target for cancer therapy.

Key words:Neoplasms,MicroRNAs,RNA-binding proteins,Neoplastic stem cells

彭景涛, 莫仁, 凡杰. 双向负反馈环路lin28-let-7与肿瘤[J]. 国际肿瘤学杂志, 2014, 41(3): 165-168.

PENG Jing-Tao, MO Ren, FAN Jie. A double-negative feedback loop lin28-let-7 and tumor[J]. Journal of International Oncology, 2014, 41(3): 165-168.

参考文献

［1］ Mathieu J, RuoholaBaker H. Regulation of stem cell populations by microRNAs［J］. Adv Exp Med Biol， 2013, 786: 329-351. ［2］ Di Leva G, Croce CM. Roles of small RNAs in tumor formation［J］. Trends Mol Med， 2010, 16(6): 257-267. ［3］ Viswanathan SR, Daley GQ. Lin28: A microRNA regulator with a macro role［J］. Cell， 2010, 140(4): 445-449. ［4］ Boyerinas B, Park SM, Hau A, et al. The role of let-7 in cell differentiation and cancer［J］. Endocr Relat Cancer， 2010, 17(1): F19-36. ［5］ Roush S, Slack FJ. The let-7 family of microRNAs［J］. Trends Cell Biol， 2008, 18(10): 505-516. ［6］ Heo I, Joo C, Cho J, et al. Lin28 mediates the terminal uridylation of let-7 precursor MicroRNA［J］. Mol Cell， 2008, 32(2): 276-284. ［7］ Piskounova E, Polytarchou C, Thornton JE, et al. Lin28A and Lin28B inhibit let-7 microRNA biogenesis by distinct mechanisms［J］. Cell, 2011, 147(5): 1066-1079. ［8］ Rybak A, Fuchs H, Smirnova L, et al. A feedback loop comprising lin-28 and let-7 controls prelet-7 maturation during neural stemcell commitment［J］. Nat Cell Biol, 2008, 10(8): 987-993. ［9］ Yamanaka S. Pluripotency and nuclear reprogramming［J］. Philos Trans R Soc Lond B Biol Sci, 2008, 363(1500):2079-2087. ［10］ Viswanathan SR, Daley GQ, Gregory RI. Selective blockade of microRNA processing by Lin28［J］. Science, 2008, 320(5872): 97-100. ［11］ Li X, Zhang J, Gao L, et al. MiR-181 mediates cell differentiation by interrupting the Lin28 and let-7 feedback circuit［J］. Cell Death Diffe, 2012, 19(3): 378-386. ［12］ Yang X, Lin X, Zhong X, et al. Double-negative feedback loop between reprogramming factor LIN28 and microRNA let-7 regulates aldehyde dehydrogenase 1-positive cancer stem cells［J］. Cancer Res, 2010, 70(22): 9463-9472. ［13］ Peng S, Maihle NJ, Huang Y. Pluripotency factors Lin28 and Oct4 identify a subpopulation of stem cell-like cells in ovarian cancer［J］. Oncogene, 2010, 29(14): 2153-2159. ［14］ Ma W, Ma J, Xu J, et al. Lin28 regulates BMP4 and functions with Oct4 to affect ovarian tumor microenvironment［J］. Cell Cycle, 2013, 12(1): 88-97. ［15］ Viswanathan SR, Powers JT, Einhorn W, et al. Lin28 promotes transformation and is associated with advanced human malignancies［J］. Nat Genet， 2009, 41(7): 843-848. ［16］ Chang TC, Zeitels LR, Hwang HW, et al. Lin-28B transactivation is necessary for Mycmediated let-7 repression and proliferation［J］. Proc Natl Acad Sci USA， 2009, 106(9): 3384-3389. ［17］ Iliopoulos D, Hirsch HA, Struhl K. An epigenetic switch involving NF-kappaB, Lin28, Let7 MicroRNA, and IL6 links inflammation to cell transformation［J］. Cell， 2009, 139(4): 693-706. ［18］ Saiki Y, Ishimaru S, Mimori K, et al. Comprehensive analysis of the clinical significance of inducing pluripotent stemnessrelated gene expression in colorectal cancer cells［J］. Ann Surg Oncol， 2009, 16(9): 2638-2644. ［19］ King CE, Cuatrecasas M, Castells A, et al. LIN28B promotes colon cancer progression and metastasis［J］. Cancer Res， 2011, 71(12): 4260-4268. ［20］ Hamano R, Miyata H, Yamasaki M, et al. High expression of Lin28 is associated with tumour aggressiveness and poor prognosis of patients in oesophagus cancer［J］. Br J Cancer， 2012, 106(8): 1415-1423. ［21］ DangiGarimella S, Yun J, Eves EM, et al. Raf kinase inhibitory protein suppresses a metastasis signalling cascade involving LIN28 and let-7［J］. EMBO J， 2009, 28(4): 347-358. ［22］ Lv K, Liu L, Wang L, et al. Lin28 mediates paclitaxel resistance by modulating p21, Rb and Let7a miRNA in breast cancer cells［J］. PLoS One， 2012, 7(7): e40008. ［23］ Jeong SH, Wu HG, Park WY. LIN28B confers radioresistance through the posttranscriptional control of KRAS［J］. Exp Mol Med， 2009, 41(12): 912-918. ［24］ Besancon R, ValsesiaWittmann S, Puisieux A, et al. Cancer stem cells: the emerging challenge of drug targeting［J］. Curr Med Chem， 2009, 16(4): 394-416. ［25］ Thornton JE, Gregory RI. How does Lin28 let7 control development and disease?［J］. Trends Cell Biol， 2012, 22(9): 474-482.

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