微RNA通过调节上皮间质转化影响肿瘤转移

doi:10.3724/SP.J.1005.2014.0637

遗传 ›› 2014, Vol. 36 ›› Issue (7): 637-645.doi: 10.3724/SP.J.1005.2014.0637

微RNA通过调节上皮间质转化影响肿瘤转移

杨丽华^{1, 2}, 沈星凯¹, 李静秋^{1, 2}, 杨杰^{1, 2}, 乐燕萍^{1, 2}, 龚朝辉^{1, 2}

1. 宁波大学医学院生物化学与分子生物学研究所, 宁波 315211;
2. 浙江省病理生理学技术研究重点实验室, 宁波 315211

收稿日期:2014-01-16 出版日期:2014-07-20 发布日期:2014-06-23
通讯作者: 龚朝辉, 博士, 教授, 研究方向：肿瘤分子生物学。E-mail: zhaohui@ncri.org.cn
作者简介:杨丽华, 硕士研究生, 专业方向：肿瘤分子生物学。Tel: 0574-87600754; E-mail: lihuayang@ncri.org.cn
基金资助:
浙江省高等学校中青年学科带头人学术攀登项目(编号：pd2013103), 浙江省科技厅公益技术应用研究项目(编号：2013C37029), 宁波市科技创新团队项目(编号：2011B82014), 宁波大学创优秀硕士论文培育基金项目(编号：PY2012010)和宁波大学王宽诚教育基金资助

MicroRNAs affect tumor metastasis through regulating epithelial- mesenchymal transition

Lihua Yang^{1, 2}, Xingkai Shen¹, Jingqiu Li^{1, 2}, Jie Yang^{1, 2}, Yanping Le^{1, 2}, Zhaohui Gong^{1, 2}

1. Institute of Biochemistry and Molecular Biology, Ningbo University School of Medicine, Ningbo 315211, China;
2. Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo 315211, China

Received:2014-01-16 Online:2014-07-20 Published:2014-06-23

摘要/Abstract

摘要： 肿瘤细胞向远处转移受多因素调控, 涉及多个基因, 需要经历一系列连续的、可选择的级联事件。上皮间质转化(Epithelial-mesenchymal transition, EMT)是肿瘤细胞转移中的关键步骤, 但肿瘤发生 EMT的机制至今尚不完全明确。微RNA (MicroRNA, miRNA)是一类内源性、非编码小分子RNA, 可在转录后水平负调控EMT相关基因的表达, 在肿瘤转移中发挥重要作用。文章主要就EMT与肿瘤转移的关系、影响EMT的转录因子, 以及miRNA通过靶向EMT相关的转录因子影响肿瘤转移等方面进行了综述。

关键词: 微RNA, 肿瘤转移, 上皮间质转化

Abstract: Distant metastasis of tumor cell is a series of continuous, selectable cascades of events regulated by multiple factors and genes. Epithelial-mesenchymal transition (EMT) is a critical step during cancer metastasis. However, the mechanism of EMT in tumor is not yet fully elucidated. MicroRNAs (miRNAs) are a class of non-coding small endogenous RNAs that negatively regulate EMT-related genes at the post-transcriptional level and play critical roles in cancer metastasis. This review mainly focuses on the topics that include the relationship of EMT and tumor metastasis, transcription factors involved in EMT, and the effect of miRNAs on tumor metastasis by targeting the EMT-related transcription factors.

Key words: microRNAs, tumor metastasis, epithelial-mesenchymal transition

杨丽华, 沈星凯, 李静秋, 杨杰, 乐燕萍, 龚朝辉. 微RNA通过调节上皮间质转化影响肿瘤转移[J]. 遗传, 2014, 36(7): 637-645.

Lihua Yang, Xingkai Shen, Jingqiu Li, Jie Yang, Yanping Le, Zhaohui Gong. MicroRNAs affect tumor metastasis through regulating epithelial- mesenchymal transition[J]. HEREDITAS(Beijing), 2014, 36(7): 637-645.

参考文献

[1] Cancer Society. Cancer Facts & Figures 2013. Atlanta: American Cancer Society, 2013.
[2] IJ. The pathogenesis of cancer metastasis: the ‘seed and soil’hypothesis revisited. Nat Rev Cancer , 2003, 3(6): 453-458.
[3] JM, Dedhar S, Kalluri R, Thompson EW. The epithelial-mesenchymal transition: new insights in signaling, development, and disease. J Cell Biol , 2006, 172(7): 973-981.
[4] DJ, Robin TP, Ford HL. Breast cancer epithelial-to-mesenchymal transition: examining the functional consequences of plasticity. Breast Cancer Res , 2011, 13(6): 226-239.
[5] DC, Labarge MA. Epithelial-mesenchymal transition and the stem cell phenotype. Cell Stem Cell , 2008, 2(6): 511-512.
[6] A, Pintzas A. Epithelial-mesenchymal transition in cancer metastasis: mechanisms, markers and strategies to overcome drug resistance in the clinic. Biochim Biophys Acta , 2009, 1796(2): 75-90.
[7] H, Ackland ML, Blick T, Lawrence MG, Clements JA, Williams ED, Thompson EW. Epithelial mesenchymal and mesenchymal epithelial transitions in carcinoma progression. J Cell Physiol , 2007, 213(2): 374-383.
[8] R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest , 2009, 119(6): 1420-1428.
[9] J, Weinberg RA. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev Cell , 2008, 14(6): 818-829.
[10] M, Peli J, Rudaz C, Schwarz H, Beug H, Reichmann E. TGF-beta1 and Ha-Ras collaborate in modulating the phenotypic plasticity and invasiveness of epithelial tumor cells. Genes Dev , 1996, 10(19): 2462-2477.
[11] EL, Walser TC, Krysan K, Liclican EL, Grant JL, Rodriguez NL, Dubinett SM. The inflammatory tumor microenvironment, epithelial mesenchymal transition and lung carcinogenesis. Cancer Microenviron , 2012, 5(1): 5-18.
[12] E, Sancho E, Franci C, Dominguez D, Monfar M, Baulida J, Garcia De Herreros A. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat Cell Biol , 2000, 2(2): 84-89.
[13] KM, Chen DY, Fearon ER. The SLUG zinc-finger protein represses E-cadherin in breast cancer. Cancer Res , 2002, 62(6): 1613-1618.
[14] J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA. Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell , 2004, 117(7): 927-939.
[15] A, Aigner K, Sonderegger S, Dampier B, Oehler S, Schreiber M, Berx G, Cano A, Beug H, Foisner R. DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells. Oncogene , 2005, 24(14): 2375-2385.
[16] C, Comijn J, De Craene B, Vermassen P, Bruyneel E, Andersen H, Tulchinsky E, Van Roy F, Berx G. SIP1/ZEB2 induces EMT by repressing genes of different epithelial cell-cell junctions. Nucleic Acids Res , 2005, 33(20): 6566-6578.
[17] KA, Muir B, Reinhardt F, Carpenter AE, Sgroi DC, Weinberg RA. The Spemann organizer gene, Goosecoid, promotes tumor metastasis. Proc Natl Acad Sci USA , 2006, 103(50): 18969-18974.
[18] SA, Yang J, Brooks M, Schwaninger G, Zhou A, Miura N, Kutok JL, Hartwell K, Richardson AL, Weinberg RA. Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers. Proc Natl Acad Sci USA , 2007, 104(24): 10069-10074.
[19] H, Meng F, Liu G, Zhang B, Zhu J, Wu F, Ethier SP, Miller F, Wu G. Forkhead transcription factor foxq1 promotes epithelial-mesenchymal transition and breast cancer metastasis. Cancer Res , 2011, 71(4): 1292-1301.
[20] X, Zheng M, Liu G, Xia W, Mckeown-Longo PJ, Hung MC, Zhao J. Kruppel-like factor 8 induces epithelial to mesenchymal transition and epithelial cell invasion. Cancer Res , 2007, 67(15): 7184-7193.
[21] OH, Corcoles R, Fabra A, Moreno-Buen G, Acloque H, Vega S, Barrallo-Gimeno A, Cano A, Nieto MA. Metastatic colonization requires the repression of the epithelial-mesenchymal transition inducer Prrx1. Cancer Cell , 2012, 22(6): 709-724.
[22] H, Quintanilla M, Cano A. Transforming growth factor beta-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions. J Biol Chem , 2003, 278(23): 21113-21123.
[23] C, Gustafsson MV, Jin S, Poellinger L, Lendahl U. Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc Natl Acad Sci USA , 2008, 105(17): 6392-6397.
[24] BP, Hung MC. Wnt, hedgehog and snail: sister pathways that control by GSK-3beta and beta-Trcp in the regulation of metastasis. Cell Cycle , 2005, 4(6): 772-776.
[25] DC, Levy DD, Littlepage LE, Liu H, Nelson CM, Fata JE, Leake D, Godden EL, Albertson DG, Nieto MA, Werb Z, Bissell MJ. Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature , 2005, 436(7047): 123-127.
[26] T, Horiuchi A, Wang C, Oka K, Ohira S, Nikaido T, Konishi I. Hypoxia attenuates the expression of E-cadhe-rin via up-regulation of SNAIL in ovarian carcinoma cells. Am J Pathol , 2003, 163(4): 1437-1447.
[27] J, Berx G, Vermassen P, Verschueren K, Van Grunsven L, Bruyneel E, Mareel M, Huylebroeck D, Van Roy F. The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion. Mol Cell , 2001, 7(6): 1267-1278.
[28] S, Tan EJ, Peinado H, Cano A, Heldin CH, Moustakas A. HMGA2 and Smads co-regulate SNAIL1 expression during induction of epithelial-to-mesenchymal transition. J Biol Chem , 2008, 283(48): 33437-33446.
[29] BL. Hypoxia stimulates hepatocyte epithelial to mesenchymal transition by hypoxia-inducible factor and transforming growth factor-beta-dependent mechanisms. Liver Int , 2010, 30(5): 669-682.
[30] ME, Murre C. Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms. Mol Cell Biol , 2000, 20(2): 429-440.
[31] S, Bastid J, Doreau A, Morel AP, Bouchet BP, Thomas C, Fauvet F, Puisieux I, Doglioni C, Piccinin S, Maestro R, Voeltzel T, Selmi A, Valsesia-Wittmann S, Caron De Fromentel C, Puisieux A. Induction of EMT by twist proteins as a collateral effect of tumor-promoting inactivation of premature senescence. Cancer Cell , 2008, 14(1): 79-89.
[32] E, Kim J, Bendesky A, Ohno-Machado L, Wolfe CJ, Yang J. Snail2 is an essential mediator of Twist1-induced epithelial mesenchymal transition and metastasis. Cancer Res , 2011, 71(1): 245-254.
[33] MA, Lwin TM, Chang AT, Kim J, Danis E, Ohno-Machado L, Yang J. Twist1-induced invadopodia formation promotes tumor metastasis. Cancer Cell , 2011, 19(3): 372-386.
[34] MH, Hsu DS, Wang HW, Wang HJ, Lan HY, Yang WH, Huang CH, Kao SY, Tzeng CH, Tai SK, Chang SY, Lee OK, Wu KJ. Bmi1 is essential in Twist1-induced epithelial-mesenchymal transition. Nat Cell Biol , 2010, 12(10): 982-992.
[35] L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature , 2007, 449(7163): 682-688.
[36] M, Lin AW, Mccurrach ME, Beach D, Lowe SW. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell , 1997, 88(5): 593-602.
[37] T, Ibaragi S, Shima K, Hu MG, Katsurano M, Sasaki A, Hu GF. Epithelial-mesenchymal transition induced by growth suppressor p12CDK2-AP1 promotes tumor cell local invasion but suppresses distant colony growth. Ca n cer Res , 2008, 68(24): 10377-10386.
[38] PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, Wykoff CC, Pugh CW, Maher ER, Ratcliffe PJ. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature , 1999, 399(6733): 271-275.
[39] R, Mudduluru G, Ceppi P, Muppala S, Kozlowski M, Niklinski J, Papotti M, Allgayer H. MicroRNA-30a inhibits epithelial-to-mesenchymal transition by targeting Snai1 and is downregulated in non-small cell lung cancer. Int J Cancer , 2012, 130(9): 2044-2053.
[40] J, Zhou J, Fu J, He T, Qin J, Wang L, Liao L, Xu J. Phosphorylation of serine 68 of Twist1 by MAPKs stabilizes Twist1 protein and promotes breast cancer cell invasiveness. Cancer Res , 2011, 71(11): 3980-3990.
[41] E, Liu Y, De Barrios O, Siles L, Fanlo L, Cuatrecasas M, Darling DS, Dean DC, Castells A, Postigo A. EMT-activating transcription factors in cancer: beyond EMT and tumor invasiveness. Cell Mol Life Sci , 2012, 69(20): 3429-3456.
[42] CP, Gregory PA, Kolesnikoff N, Bert AG, Wang J, Shannon MF, Goodall GJ. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Res , 2008, 68(19): 7846-7854.
[43] J, Ma L. MicroRNA control of epithelial-mesenchymal transition and metastasis. Cancer Meta s tasis Rev , 2012, 31(3-4): 653-662.
[44] BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell , 2005, 120(1): 15-20.
[45] X, Chen Z, Zhao X, Wang J, Ding D, Wang Z, Tan F, Tan X, Zhou F, Sun J, Sun N, Gao Y, Shao K, Li N, Qiu B, He J. MicroRNA-25 promotes cell migration and invasion in esophageal squamous cell carcinoma. Biochem Biophys Res Commun , 2012, 421(4): 640-645.
[46] L, Young J, Prabhala H, Pan E, Mestdagh P, Muth D, Teruya-Feldstein J, Reinhardt F, Onder TT, Valastyan S, Westermann F, Speleman F, Vandesompele J, Weinberg RA. miR-9, a MYC/MYCN-activated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol , 2010, 12(3): 247-256.
[47] X, Wang C, Chen Z, Jin Y, Wang Y, Kolokythas A, Dai Y, Zhou X. MicroRNA-138 suppresses epithelial-mesenchymal transition in squamous cell carcinoma cell lines. Biochem J , 2011, 440(1): 23-31.
[48] PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y, Goodall GJ. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol , 2008, 10(5): 593-601.
[49] M, Seike M, Soeno C, Mizutani H, Kitamura K, Minegishi Y, Noro R, Yoshimura A, Cai L, Gemma A. MiR-23a regulates TGF-beta-induced epithelial-mesenchymal transition by targeting E-cadherin in lung cancer cells. Int J Oncol , 2012, 41(3): 869-875.
[50] NH, Kim HS, Li XY, Lee I, Choi HS, Kang SE, Cha SY, Ryu JK, Yoon D, Fearon ER, Rowe RG, Lee S, Maher CA, Weiss SJ, Yook JI. A p53/miRNA-34 axis regulates Snail1-dependent cancer cell epithelial-mesenchymal transition. J Cell Biol , 2011, 195(3): 417-433.
[51] G, Rosato A, Ferrari F, Manfrin A, Cordenonsi M, Dupont S, Enzo E, Guzzardo V, Rondina M, Spruce T, Parenti AR, Daidone MG, Bicciato S, Piccolo S. A MicroRNA targeting dicer for metastasis control. Cell , 2010, 141(7): 1195-1207.
[52] Z, Dai Y, Zhang L, Jiang C, Li Z, Yang J, Mccarthy JB, She X, Zhang W, Ma J, Xiong W, Wu M, Lu J, Li X, Li X, Xiang J, Li G. miR-18a promotes malignant progression by impairing microRNA biogenesis in nasopharyngeal carcinoma. Carcinogenesis , 2013, 34(2): 415-425.
[53] CA, Zatloukal K, Martinez J. miR-29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis. EMBO Rep , 2009, 10(4): 400-405.
[54] Z, Liu S, Shi R, Zhao G. miR-27 promotes human gastric cancer cell metastasis by inducing epithelial-to-mesenchymal transition. Cancer Genet , 2011, 204(9): 486-491.
[55] ZT, Cai MY, Wang XG, Kong LL, Mai SJ, Liu YH, Zhang HB, Liao YJ, Zheng F, Zhu W, Liu TH, Bian XW, Guan XY, Lin MC, Zeng MS, Zeng YX, Kung HF, Xie D. EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and Snail to inhibit E-cadherin. Onc o gene , 2012, 31(5): 583-594.
[56] Y, Massague J. Epithelial-mesenchymal transitions: twist in development and metastasis. Cell , 2004, 118(3): 277-279.
[57] M, Lee ES, Hu G, Kang Y. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem , 2008, 283(22): 14910-14914.
[58] JM, Chakraborty AK. Fusion of tumour cells with bone marrow-derived cells: a unifying explanation for metastasis. Nat Rev Cancer , 2008, 8(5): 377-386.
[59] PS, Rustgi AK. The role of the miR-200 family in epithelial-mesenchymal transition. Cancer Biol Ther , 2010, 10(3): 219-222.
[60] DL, Lin W, Creighton CJ, Rizvi ZH, Gregory PA, Goodall GJ, Thilaganathan N, Du L, Zhang Y, Pertsemlidis A, Kurie JM. Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression. Genes Dev , 2009, 23(18): 2140-2151.
[61] Y, Ahn YH, Gibbons DL, Zang Y, Lin W, Thilaganathan N, Alvarez CA, Moreira DC, Creighton CJ, Gregory PA, Goodall GJ, Kurie JM. The Notch ligand Jagged2 promotes lung adenocarcinoma metastasis through a miR-200-dependent pathway in mice. J Clin Invest , 2011, 121(4): 1373-1385.
[62] Q, Yang M, Lan H, Yu X. miR-30a negatively regulates TGF-beta1-induced epithelial-mesenchymal transition and peritoneal fibrosis by targeting Snai1. Am J Pathol , 2013, 183(3): 808-819.
[63] E, Caudy AA, Hammond SM, Hannon GJ. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature , 2001, 409(6818): 363-366.
[64] G, Mclachlan J, Pasquinelli AE, Balint E, Tuschl T, Zamore PD. A cellular function for the RNA-interference enzyme Dicer in the maturation of the let-7 small temporal RNA. Science , 2001, 293(5531): 834-838.
[65] DP. MicroRNAs: target recognition and regulatory functions. Cell , 2009, 136(2): 215-233.
[66] MS, Pester RE, Chen CY, Lane K, Chin C, Lu J, Kirsch DG, Golub TR, Jacks T. Dicer1 functions as a haploinsufficient tumor suppressor. Genes Dev , 2009, 23(23): 2700-2704.
[67] MS, Da Silva-Diz V, Carmona FJ, Ramalho-Carvalho J, Heyn H, Villanueva A, Munoz P, Esteller M. Impaired DICER1 function promotes stemness and metastasis in colon cancer. Oncogene , 2013, [Epub ahead of print].
[68] G, Voirin N, Ay AS, Cox DG, Chabaud S, Treilleux I, Leon-Goddard S, Rimokh R, Mikaelian I, Venoux C, Puisieux A, Lasset C, Moyret-Lalle C. Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype. Br J Cancer , 2009, 101(4): 673-683.
[69] X, Chakravarti D, Cho MS, Liu L, Gi YJ, Lin YL, Leung ML, El-Naggar A, Creighton CJ, Suraokar MB, Wistuba I, Flores ER. TAp63 suppresses metastasis through coordinate regulation of Dicer and miRNAs. N a ture , 2010, 467(7318): 986-990.
[70] M. Nuclear factor-kappaB in cancer development and progression. Nature , 2006, 441(7092): 431-436.
[71] Waes C. Nuclear factor-kappaB in development, prevention, and therapy of cancer. Clin Cancer Res , 2007, 13(4): 1076-1082.
[72] G, Sung B, Aggarwal BB. Nuclear factor-kappaB activation: from bench to bedside. Exp Biol Med ( Ma y wood ), 2008, 233(1): 21-31.
[73] ZM, Pu YW, Zhu BS. Blockade of NF-kappaB nuclear translocation results in the inhibition of the invasiveness of human gastric cancer cells. Oncol Lett , 2013, 6(2): 432-436.
[74] SF, Alarcon C, Oskarsson T, Padua D, Wang Q, Bos PD, Gerald WL, Massague J. Endogenous human microRNAs that suppress breast cancer metastasis. Nature , 2008, 451(7175): 147-152.
[75] Q, Gumireddy K, Schrier M, Le Sage C, Nagel R, Nair S, Egan DA, Li A, Huang G, Klein-Szanto AJ, Gimotty PA, Katsaros D, Coukos G, Zhang L, Pure E, Agami R. The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol , 2008, 10(2): 202-210.
[76] JE, Santoro MM, Morton SU, Yu S, Yeh RF, Wythe JD, Ivey KN, Bruneau BG, Stainier DY, Srivastava D. miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell , 2008, 15(2): 272-284.
[77] TA, Yamakuchi M, Ferlito M, Mendell JT, Lowenstein CJ. MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule. Proc Natl Acad Sci USA , 2008, 105(5): 1516-1521.
[78] H, Zhu S, Mo YY. Suppression of cell growth and invasion by miR-205 in breast cancer. Cell Res , 2009, 19(4): 439-448.
[79] M, Di Leva G, Romano G, Nuovo G, Suh SS, Ngankeu A, Taccioli C, Pichiorri F, Alder H, Secchiero P, Gasparini P, Gonelli A, Costinean S, Acunzo M, Condorelli G, Croce CM. miR-221 & 222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. Cancer Cell , 2009, 16(6): 498-509.
[80] SJ, Lai SC, Wood LW, Helsley KR, Runkle EA, Winslow MM, Mu D. MicroRNA-33a mediates the regulation of high mobility group AT-hook 2 gene (HMGA2) by thyroid transcription factor 1 (TTF-1/NKX2-1). J Biol Chem , 2013, 288(23): 16348-16360.
[81] X, Liu T, Fang O, Leach LJ, Hu X, Luo Z. miR-194 suppresses metastasis of non-small cell lung cancer through regulating expression of BMP1 and p27. Onc o gene , 2014, 33(12): 1506-1514.
[82] S, Kim K, Jin UH, Pfent C, Cao H, Amendt B, Liu X, Wilson-Robles H, Safe S. Aryl hydrocarbon receptor agonists induce microRNA-335 expression and inhibit lung metastasis of estrogen receptor negative breast cancer cells. Mol Cancer Ther , 2012, 11(1): 108-118.
[83] Y, Zhong Z, Huang Y, Deng W, Cao J, Tsao G, Liu Q, Pei D, Kang T, Zeng YX. Stem-like cancer cells are inducible by increasing genomic instability in cancer cells. J Biol Chem , 2010, 285(7): 4931-4940.
[84] JM, Lee CR, Cruz-Munoz W, Bjarnason GA, Christensen JG, Kerbel RS. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell , 2009, 15(3): 232-239.
[85] CJ, Li X, Landis M, Dixon JM, Neumeister VM, Sjolund A, Rimm DL, Wong H, Rodriguez A, Herschkowitz JI, Fan C, Zhang X, He X, Pavlick A, Gutierrez MC, Renshaw L, Larionov AA, Faratian D, Hilsenbeck SG, Perou CM, Lewis MT, Rosen JM, Chang JC. Residual breast cancers after conventional therapy display mesenchymal as well as tumor-initiating features. Proc Natl Acad Sci USA , 2009, 106(33): 13820-13825.

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号
总访问:,今日访问:,当前在线:

微RNA通过调节上皮间质转化影响肿瘤转移

MicroRNAs affect tumor metastasis through regulating epithelial- mesenchymal transition

PDF (PC)

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 6

编辑推荐

Metrics

[1]	李静秋, 杨杰, 周平, 乐燕萍, 龚朝辉. 竞争性内源RNA的生物学功能及其调控[J]. 遗传, 2015, 37(8): 756-764.
[2]	赵承孝, 杨泽. Twist2的生物学功能及其分子机制[J]. 遗传, 2015, 37(1): 17-24.
[3]	杨丽华，董琢，龚朝辉. 细胞外微RNA：一种新型的肺癌分子生物标志物[J]. 遗传, 2012, 34(6): 651-658.
[4]	史忠诚，于旸，李钰，傅松滨. rab5a基因在肿瘤转移中的作用研究[J]. 遗传, 2005, 27(5): 694-698.
[5]	黄昀，杨焕杰，金焰，李慧敏，傅松滨. 13q14断裂重排与非小细胞肺癌转移潜能关系的研究[J]. 遗传, 2005, 27(4): 531-534.
[6]	李钰，宋岩，陆纲，邹荣，邹亚男，张贵寅，李璞. 一个与非小细胞肺癌转移相关的基因――RAB5A基因[J]. 遗传, 1999, 21(4): 6-10.