高迁移率蛋白A2在肿瘤中的表达及作用机制

摘要/Abstract

摘要： 高迁移率蛋白A2（HMGA2）是一种非组蛋白染色质相关蛋白，其AT钩结构能够特异性结合特定的DNA序列，主要功能是作为致癌基因和结构转录因子。HMGA2几乎在所有类型的恶性肿瘤中表达，与肿瘤的形成、发展以及不良预后密切相关。HMGA2在各个生物过程，包括细胞增殖、细胞周期、干细胞自我更新、上皮间质转化及DNA损伤修复中都起到了重要作用。深入研究高迁移率蛋白A2对肿瘤的影响及其作用机制具有重大意义。

关键词: MGA2蛋白, 肿瘤, 基因表达, 作用机制

Abstract: The high mobility group A2 (HMGA2), one of nonhistone chromatin protein, can specificly bind to ATrich DNA sequences by its AThook and work as oncofetal gene and architectural transcription factor. HMGA2 expresses in almost all kinds of malignant neoplasms, which is closely related to the formation, development and poor prognosis of the neoplasms. HMGA2 plays a very important role in every biological process including cell proliferation, cell cycle, stem cell selfrenewal, epithelialmesenchymal transition and DNA damage repair. It is of great significance to study the effect and mechanism of HMGA2 in neoplasms.

Key words: HMGA2 protein, Neoplasms, Gene expression, Functional mechanism

李青, 卢颖, 张春影, 毛俊, 李连宏. 高迁移率蛋白A2在肿瘤中的表达及作用机制[J]. 国际肿瘤学杂志, 2016, 43(2): 106-.

LI Qing, LU Ying, ZHANG Chun-Ying, MAO Jun, LI Lian-Hong. Expression and functional mechanism of high mobility group A2 in neoplasm[J]. Journal of International Oncology, 2016, 43(2): 106-.

参考文献

［1］ Zha L, Zhang J, Tang W, et al. HMGA2 elicits EMT by activating the Wnt/βcatenin pathway in gastric cancer［J］. Dig Dis Sci, 2013, 58(3): 724733. DOI:10.1007/s1062001223996. ［2］ Kong DQ, Su GQ, Zha L, et al. Coexpression of HMGA2 and Oct4 predicts an unfavorable prognosis in human gastric cancer［J］. Med Oncol, 2014, 31(8): 130139. DOI:10.1007/s1203201401305. ［3］ Wang XC, Liu XY, Li AY, et al. Overexpression of HMGA2 promotes metastasis and impacts survival of colorectal cancers［J］. Clin Cancer Res, 2011, 17(8): 25702580. DOI:10.1158/10780432.CCR102542. ［4］ Wu Y, Song Y, Liu H. Expression and its clinical significance of HMGA2 in the patients with nonsmall cell lung cancer［J］. Zhongguo Fei Ai Za Zhi, 2008, 11(3): 377381. DOI:10.3779/j.issn.10093419.2008.03.005. ［5］ Di Cello F, Hillion J, Hristov A, et al. HMGA2 participates in transformation in human lung cancer［J］. Mol Cancer Res, 2008, 6(5): 743750. DOI:10.1158/15417786.MCR070095. ［6］ Kumar MS, ArmenterosMonterroso E, East P, et al. HMGA2 functions as a competing endogenous RNA to promote lung cancer progression［J］. Nature, 2014, 505(7482): 212217. DOI:10.1038/nature12785. ［7］ Califano D, Pignata S, Losito NS, et al. High HMGA2 expression and high body mass index negatively affect the prognosis of patients with ovarian cancer［J］. J Cell Physiol, 2014, 229(1): 5359. DOI:10.1002/jcp.24416. ［8］ Malek A, Bakhidze E, Noske A, et al. HMGA2 gene is a promising target for ovarian cancer silencing therapy［J］. Int J Cancer, 2008, 123(2): 348356. DOI:10.1002/ijc.23491. ［9］ Morishita A, Zaidi MR, Mitoro AA, et al. HMGA2 is a driver of tumor metastasis［J］. Cancer Res, 2013, 73(14): 42894299. DOI:10.1158/00085472.CAN123848. ［10］ Sun M, Song CX, Huang H, et al. HMGA2/TET1/HOXA9 signaling pathway regulates breast cancer growth and metastasis［J］. Proc Natl Acad Sci USA, 2013, 110(24): 99209925. DOI:10.1073/pnas.1305172110. ［11］ Yang GL, Zhang LH, Bo JJ, et al. Overexpression of HMGA2 in bladder cancer and its association with clinicopathologic features and prognosis［J］. Eur J Surg Oncol, 2011, 37(3): 265271. ［12］ Liu B, Pang B, Hou XZ, et al. Expression of highmobility group AThook protein 2 and its prognostic significance in malignant gliomas［J］. Hum Pathol, 2014, 45(8): 17521758. DOI:10.1016/j.humpath.2014.02.028. ［13］ Yamazaki H, Mori T, Yazawa M, et al. Stem cell selfrenewal factors Bmi1 and HMGA2 in head and neck squamous cell carcinoma: clues for diagnosis［J］. Lab Invest, 2013, 93(12): 13311338. DOI:10.1038/labinvest.2013.120. ［14］ Thuault S, Tan EJ, Peinado H, et al. HMGA2 and smads coregulate SNAIL1 expression during induction of EpithelialtoMesenchymal transition［J］. J Biol Chem, 2008, 283(48): 3343733446. DOI:10.1074/jbc.M802016200. ［15］ Li Y, Zhao ZX, Xu CH, et al. HMGA2 induces transcription factor Slug expression to promote epithelialtomesenchymal transition and contributes to colon cancer progression［J］. Cancer Lett, 2014, 355(1): 130140. DOI:10.1016/j.canlet.2014.09.007. ［16］ Ikeda K, Ogawa K, Takeishi Y. The role of HMGA2 in the proliferation and expansion of a hematopoietic cell in myeloproliferative neoplasms［J］. Fukushima J Med Sci, 2012, 58(2): 91100. ［17］ Morshedi A, Ren ZL, Li JM, et al. Probing into the biological processes influenced by ESC factor and oncoprotein HMGA2 using iPSCs［J］. Stem Cell Rev, 2013, 9(4): 514522. DOI:10.1007/s1201501293738. ［18］ Nishino J, Kim I, Chada K, et al. Hmga2 promotes neural stem cell selfrenewal in young but not old mice by reducing p16Ink4a and p19Arf expression［J］. Cell, 2008, 135(2): 227239. DOI:10.1016/j.cell.2008.09.017. ［19］ Fedele M, Visone R, De Martino I, et al. HMGA2 induces pituitary tumorigenesis by enhancing E2F1 activity［J］. Cancer Cell, 2006, 9(6): 459471. DOI:10.1016/j.ccr.2006.04.024. ［20］ De Martino I, Visone R, Wierinckx A, et al. HMGA proteins upregulate CCNB2 gene in mouse and human pituitary adenomas［J］. Cancer Res, 2009, 69(5): 18441850. DOI:10.1158/00085472.CAN084133. ［21］ Tessari MA, Gostissa M, Altamura S, et al. Transcriptional activation of the cyclin A gene by the architectural transcription factor HMGA2［J］. Mol Cell Biol, 2003, 23(24): 91049116. DOI:10.1128/MCB.23.24.91049116.2003. ［22］ Yu HJ, Lim HH, Tjokro NO, et al. Chaperoning HMGA2 protein protects stalled replication forks in stem and cancer cells［J］. Cell Rep, 2014, 6(4): 684697. DOI:10.1016/j.celrep.2014.01.014. ［23］ Li AY, Boo LM, Wang SY, et al. Suppression of nonhomologous end joining repair by overexpression of HMGA2［J］. Cancer Res, 2009, 69(14): 56995706. DOI:10.1158/00085472.CAN084833. ［24］ Borrmann L, Schwanbeck R, Heyduk T, et al. High mobility group A2 protein and its derivatives bind a specific region of the promoter of DNA repair gene ERCC1 and modulate its activity［J］. Nucleic Acids Res, 2003, 31(23): 68416851. DOI:10.1093/nar/gkg884. ［25］ Natarajan S, HombachKlonisch S, Droege PA. HMGA2 inhibits apoptosis through interaction with ATRCHK1 signaling complex in human cancer cells［J］. Neoplasia, 2013, 15(3): 263. DOI:10.1593/neo.121988.

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