Please use this identifier to cite or link to this item:
標題: Let-7b於小鼠子宮內膜細胞與黑色素腫瘤細胞中對Basigin與細胞生理的功能分析
Functional analysis of let-7b in Basigin expression and cellular physiology of melanoma cells and endometrial cells in mice
作者: 傅子彥
Fu, Tzu-Yen
關鍵字: let-7b;微型RNA;microRNA;tumor;implantation;endometrium;melanoma cells;腫瘤;著床;子宮內膜;黑色素腫瘤細胞
出版社: 動物科學系所
引用: [1] D.P. Bartel, MicroRNAs: target recognition and regulatory functions, Cell 136 (2009) 215-233. [2] R.W. Carthew, E.J. Sontheimer, Origins and Mechanisms of miRNAs and siRNAs, Cell 136 (2009) 642-655. [3] J. Krol, I. Loedige, W. Filipowicz, The widespread regulation of microRNA biogenesis, function and decay, Nat Rev Genet 11 (2010) 597-610. [4] G. Tang, siRNA and miRNA: an insight into RISCs, Trends Biochem Sci 30 (2005) 106-114. [5] S.M. Hammond, Dicing and slicing: the core machinery of the RNA interference pathway, FEBS Lett 579 (2005) 5822-5829. [6] G. Meister, M. Landthaler, A. Patkaniowska, Y. Dorsett, G. Teng, T. Tuschl, Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs, Mol Cell 15 (2004) 185-197. [7] J.B. Preall, E.J. Sontheimer, RNAi: RISC gets loaded, Cell 123 (2005) 543-545. [8] P. Sethupathy, B. Corda, A.G. Hatzigeorgiou, TarBase: A comprehensive database of experimentally supported animal microRNA targets, RNA 12 (2006) 192-197. [9] G. Meister, T. Tuschl, Mechanisms of gene silencing by double-stranded RNA, Nature 431 (2004) 343-349. [10] R.S. Pillai, S.N. Bhattacharyya, W. Filipowicz, Repression of protein synthesis by miRNAs: how many mechanisms?, Trends Cell Biol 17 (2007) 118-126. [11] A. Krek, D. Grun, M.N. Poy, R. Wolf, L. Rosenberg, E.J. Epstein, P. MacMenamin, I. da Piedade, K.C. Gunsalus, M. Stoffel, N. Rajewsky, Combinatorial microRNA target predictions, Nat Genet 37 (2005) 495-500. [12] B.J. Reinhart, F.J. Slack, M. Basson, A.E. Pasquinelli, J.C. Bettinger, A.E. Rougvie, H.R. Horvitz, G. Ruvkun, The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans, Nature 403 (2000) 901-906. [13] A.E. Pasquinelli, B.J. Reinhart, F. Slack, M.Q. Martindale, M.I. Kuroda, B. Maller, D.C. Hayward, E.E. Ball, B. Degnan, P. Muller, J. Spring, A. Srinivasan, M. Fishman, J. Finnerty, J. Corbo, M. Levine, P. Leahy, E. Davidson, G. Ruvkun, Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA, Nature 408 (2000) 86-89. [14] B. Boyerinas, S.M. Park, A. Hau, A.E. Murmann, M.E. Peter, The role of let-7 in cell differentiation and cancer, Endocr Relat Cancer 17 (2010) F19-36. [15] S. Roush, F.J. Slack, The let-7 family of microRNAs, Trends Cell Biol 18 (2008) 505-516. [16] J.G. Ruby, C. Jan, C. Player, M.J. Axtell, W. Lee, C. Nusbaum, H. Ge, D.P. Bartel, Large-scale sequencing reveals 21U-RNAs and additional microRNAs and endogenous siRNAs in C. elegans, Cell 127 (2006) 1193-1207. [17] J.J. Lancman, N.C. Caruccio, B.D. Harfe, A.E. Pasquinelli, J.J. Schageman, A. Pertsemlidis, J.F. Fallon, Analysis of the regulation of lin-41 during chick and mouse limb development, Dev Dyn 234 (2005) 948-960. [18] S. Liu, Q. Xia, P. Zhao, T. Cheng, K. Hong, Z. Xiang, Characterization and expression patterns of let-7 microRNA in the silkworm (Bombyx mori), BMC Dev Biol 7 (2007) 88. [19] L.F. Sempere, E.B. Dubrovsky, V.A. Dubrovskaya, E.M. Berger, V. Ambros, The expression of the let-7 small regulatory RNA is controlled by ecdysone during metamorphosis in Drosophila melanogaster, Dev Biol 244 (2002) 170-179. [20] F.G. Wulczyn, L. Smirnova, A. Rybak, C. Brandt, E. Kwidzinski, O. Ninnemann, M. Strehle, A. Seiler, S. Schumacher, R. Nitsch, Post-transcriptional regulation of the let-7 microRNA during neural cell specification, FASEB J 21 (2007) 415-426. [21] B.R. Schulman, A. Esquela-Kerscher, F.J. Slack, Reciprocal expression of lin-41 and the microRNAs let-7 and mir-125 during mouse embryogenesis, Dev Dyn 234 (2005) 1046-1054. [22] J.M. Thomson, J. Parker, C.M. Perou, S.M. Hammond, A custom microarray platform for analysis of microRNA gene expression, Nat Methods 1 (2004) 47-53. [23] S.M. Park, S. Shell, A.R. Radjabi, R. Schickel, C. Feig, B. Boyerinas, D.M. Dinulescu, E. Lengyel, M.E. Peter, Let-7 prevents early cancer progression by suppressing expression of the embryonic gene HMGA2, Cell Cycle 6 (2007) 2585-2590. [24] Y. Akao, Y. Nakagawa, T. Naoe, let-7 microRNA functions as a potential growth suppressor in human colon cancer cells, Biol Pharm Bull 29 (2006) 903-906. [25] S.M. Johnson, H. Grosshans, J. Shingara, M. Byrom, R. Jarvis, A. Cheng, E. Labourier, K.L. Reinert, D. Brown, F.J. Slack, RAS is regulated by the let-7 microRNA family, Cell 120 (2005) 635-647. [26] K. Motoyama, H. Inoue, Y. Nakamura, H. Uetake, K. Sugihara, M. Mori, Clinical significance of high mobility group A2 in human gastric cancer and its relationship to let-7 microRNA family, Clin Cancer Res 14 (2008) 2334-2340. [27] Y. Peng, J. Laser, G. Shi, K. Mittal, J. Melamed, P. Lee, J.J. Wei, Antiproliferative effects by Let-7 repression of high-mobility group A2 in uterine leiomyoma, Mol Cancer Res 6 (2008) 663-673. [28] J. Schultz, P. Lorenz, G. Gross, S. Ibrahim, M. Kunz, MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with anchorage-independent growth, Cell Res 18 (2008) 549-557. [29] S. Shell, S.M. Park, A.R. Radjabi, R. Schickel, E.O. Kistner, D.A. Jewell, C. Feig, E. Lengyel, M.E. Peter, Let-7 expression defines two differentiation stages of cancer, Proc Natl Acad Sci U S A 104 (2007) 11400-11405. [30] J. Takamizawa, H. Konishi, K. Yanagisawa, S. Tomida, H. Osada, H. Endoh, T. Harano, Y. Yatabe, M. Nagino, Y. Nimura, T. Mitsudomi, T. Takahashi, Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival, Cancer Res 64 (2004) 3753-3756. [31] N. Yanaihara, N. Caplen, E. Bowman, M. Seike, K. Kumamoto, M. Yi, R.M. Stephens, A. Okamoto, J. Yokota, T. Tanaka, G.A. Calin, C.G. Liu, C.M. Croce, C.C. Harris, Unique microRNA molecular profiles in lung cancer diagnosis and prognosis, Cancer Cell 9 (2006) 189-198. [32] H. Yang, W. Kong, L. He, J.J. Zhao, J.D. O''Donnell, J. Wang, R.M. Wenham, D. Coppola, P.A. Kruk, S.V. Nicosia, J.Q. Cheng, MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN, Cancer Res 68 (2008) 425-433. [33] T. Kanekura, X. Chen, T. Kanzaki, Basigin (CD147) is expressed on melanoma cells and induces tumor cell invasion by stimulating production of matrix metalloproteinases by fibroblasts, Int J Cancer 99 (2002) 520-528. [34] M.E. Peter, Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression, Cell Cycle 8 (2009) 843-852. [35] C. Mayr, M.T. Hemann, D.P. Bartel, Disrupting the pairing between let-7 and Hmga2 enhances oncogenic transformation, Science 315 (2007) 1576-1579. [36] A. Legesse-Miller, O. Elemento, S.J. Pfau, J.J. Forman, S. Tavazoie, H.A. Coller, let-7 Overexpression leads to an increased fraction of cells in G2/M, direct down-regulation of Cdc34, and stabilization of Wee1 kinase in primary fibroblasts, J Biol Chem 284 (2009) 6605-6609. [37] C.H. Lawrie, J. Chi, S. Taylor, D. Tramonti, E. Ballabio, S. Palazzo, N.J. Saunders, F. Pezzella, J. Boultwood, J.S. Wainscoat, C.S. Hatton, Expression of microRNAs in diffuse large B cell lymphoma is associated with immunophenotype, survival and transformation from follicular lymphoma, J Cell Mol Med 13 (2009) 1248-1260. [38] L. Lu, D. Katsaros, I.A. de la Longrais, O. Sochirca, H. Yu, Hypermethylation of let-7a-3 in epithelial ovarian cancer is associated with low insulin-like growth factor-II expression and favorable prognosis, Cancer Res 67 (2007) 10117-10122. [39] B. Brueckner, C. Stresemann, R. Kuner, C. Mund, T. Musch, M. Meister, H. Sultmann, F. Lyko, The human let-7a-3 locus contains an epigenetically regulated microRNA gene with oncogenic function, Cancer Res 67 (2007) 1419-1423. [40] M. Guled, L. Lahti, P.M. Lindholm, K. Salmenkivi, I. Bagwan, A.G. Nicholson, S. Knuutila, CDKN2A, NF2, and JUN are dysregulated among other genes by miRNAs in malignant mesothelioma -A miRNA microarray analysis, Genes Chromosomes Cancer 48 (2009) 615-623. [41] H. Wang, S.K. Dey, Roadmap to embryo implantation: clues from mouse models, Nat Rev Genet 7 (2006) 185-199. [42] S.K. Dey, H. Lim, S.K. Das, J. Reese, B.C. Paria, T. Daikoku, H. Wang, Molecular cues to implantation, Endocr Rev 25 (2004) 341-373. [43] D.D. Carson, I. Bagchi, S.K. Dey, A.C. Enders, A.T. Fazleabas, B.A. Lessey, K. Yoshinaga, Embryo implantation, Dev Biol 223 (2000) 217-237. [44] Y. Tan, D. Tan, M. He, M. Gu, Z. Wang, G. Zeng, E. Duan, A model for implantation: coculture of blastocysts and uterine endometrium in mice, Biol Reprod 72 (2005) 556-561. [45] A. Chakrabarty, S. Tranguch, T. Daikoku, K. Jensen, H. Furneaux, S.K. Dey, MicroRNA regulation of cyclooxygenase-2 during embryo implantation, Proc Natl Acad Sci U S A 104 (2007) 15144-15149. [46] X.H. Ma, S.J. Hu, H. Ni, Y.C. Zhao, Z. Tian, J.L. Liu, G. Ren, X.H. Liang, H. Yu, P. Wan, Z.M. Yang, Serial analysis of gene expression in mouse uterus at the implantation site, J Biol Chem 281 (2006) 9351-9360. [47] J. Reese, S.K. Das, B.C. Paria, H. Lim, H. Song, H. Matsumoto, K.L. Knudtson, R.N. DuBois, S.K. Dey, Global gene expression analysis to identify molecular markers of uterine receptivity and embryo implantation, J Biol Chem 276 (2001) 44137-44145. [48] S.J. Hu, G. Ren, J.L. Liu, Z.A. Zhao, Y.S. Yu, R.W. Su, X.H. Ma, H. Ni, W. Lei, Z.M. Yang, MicroRNA expression and regulation in mouse uterus during embryo implantation, J Biol Chem 283 (2008) 23473-23484. [49] H.F. Xia, X.H. Jin, P.P. Song, Y. Cui, C.M. Liu, X. Ma, Temporal and spatial regulation of let-7a in the uterus during embryo implantation in the rat, J Reprod Dev 56 (2010) 73-78. [50] H.F. Xia, X.H. Jin, P.P. Song, Y. Cui, C.M. Liu, X. Ma, Temporal and Spatial Regulation of miR-320 in the Uterus during Embryo Implantation in the Rat, Int J Mol Sci 11 (2010) 719-730. [51] I.F. Mizukami, S.D. Vinjamuri, F. Perini, D.Y. Liu, R.F. Todd, 3rd, Purification, biochemical composition, and biosynthesis of the Mo3 activation antigen expressed on the plasma membrane of human mononuclear phagocytes, J Immunol 147 (1991) 1331-1337. [52] N. Kuno, K. Kadomatsu, Q.W. Fan, M. Hagihara, T. Senda, S. Mizutani, T. Muramatsu, Female sterility in mice lacking the basigin gene, which encodes a transmembrane glycoprotein belonging to the immunoglobulin superfamily, FEBS Lett 425 (1998) 191-194. [53] L.J. Xiao, H. Chang, N.Z. Ding, H. Ni, K. Kadomatsu, Z.M. Yang, Basigin expression and hormonal regulation in mouse uterus during the peri-implantation period, Mol Reprod Dev 63 (2002) 47-54. [54] L.J. Xiao, H.L. Diao, X.H. Ma, N.Z. Ding, K. Kadomatsu, T. Muramatsu, Z.M. Yang, Basigin expression and hormonal regulation in the rat uterus during the peri-implantation period, Reproduction 124 (2002) 219-225. [55] C. Biswas, Tumor cell stimulation of collagenase production by fibroblasts, Biochem Biophys Res Commun 109 (1982) 1026-1034. [56] C. Biswas, Collagenase stimulation in cocultures of human fibroblasts and human tumor cells, Cancer Lett 24 (1984) 201-207. [57] R. Li, L. Huang, H. Guo, B.P. Toole, Basigin (murine EMMPRIN) stimulates matrix metalloproteinase production by fibroblasts, J Cell Physiol 186 (2001) 371-379. [58] D.P. Bartel, MicroRNAs: genomics, biogenesis, mechanism, and function, Cell 116 (2004) 281-297. [59] Q. Pan, N. Chegini, MicroRNA signature and regulatory functions in the endometrium during normal and disease states, Semin Reprod Med 26 (2008) 479-493. [60] K. Qian, L. Hu, H. Chen, H. Li, N. Liu, Y. Li, J. Ai, G. Zhu, Z. Tang, H. Zhang, Hsa-miR-222 is involved in differentiation of endometrial stromal cells in vitro, Endocrinology 150 (2009) 4734-4743. [61] E.M. Teague, C.G. Print, M.L. Hull, The role of microRNAs in endometriosis and associated reproductive conditions, Hum Reprod Update 16 (2010) 142-165. [62] S.D. Fiedler, M.Z. Carletti, X. Hong, L.K. Christenson, Hormonal regulation of MicroRNA expression in periovulatory mouse mural granulosa cells, Biol Reprod 79 (2008) 1030-1037. [63] S. Kuokkanen, B. Chen, L. Ojalvo, L. Benard, N. Santoro, J.W. Pollard, Genomic profiling of microRNAs and messenger RNAs reveals hormonal regulation in microRNA expression in human endometrium, Biol Reprod 82 (2010) 791-801. [64] R. Hoekstra, F.A. Eskens, J. Verweij, Matrix metalloproteinase inhibitors: current developments and future perspectives, Oncologist 6 (2001) 415-427. [65] K.T. Iacono, A.L. Brown, M.I. Greene, S.J. Saouaf, CD147 immunoglobulin superfamily receptor function and role in pathology, Exp Mol Pathol 83 (2007) 283-295. [66] T. Igakura, K. Kadomatsu, T. Kaname, H. Muramatsu, Q.W. Fan, T. Miyauchi, Y. Toyama, N. Kuno, S. Yuasa, M. Takahashi, T. Senda, O. Taguchi, K. Yamamura, K. Arimura, T. Muramatsu, A null mutation in basigin, an immunoglobulin superfamily member, indicates its important roles in peri-implantation development and spermatogenesis, Dev Biol 194 (1998) 152-165. [67] L. Chen, R.J. Belton, Jr., R.A. Nowak, Basigin-mediated gene expression changes in mouse uterine stromal cells during implantation, Endocrinology 150 (2009) 966-976. [68] B. Kefas, J. Godlewski, L. Comeau, Y. Li, R. Abounader, M. Hawkinson, J. Lee, H. Fine, E.A. Chiocca, S. Lawler, B. Purow, microRNA-7 inhibits the epidermal growth factor receptor and the Akt pathway and is down-regulated in glioblastoma, Cancer Res 68 (2008) 3566-3572. [69] F. Yu, H. Yao, P. Zhu, X. Zhang, Q. Pan, C. Gong, Y. Huang, X. Hu, F. Su, J. Lieberman, E. Song, let-7 regulates self renewal and tumorigenicity of breast cancer cells, Cell 131 (2007) 1109-1123. [70] A. Esquela-Kerscher, P. Trang, J.F. Wiggins, L. Patrawala, A. Cheng, L. Ford, J.B. Weidhaas, D. Brown, A.G. Bader, F.J. Slack, The let-7 microRNA reduces tumor growth in mouse models of lung cancer, Cell Cycle 7 (2008) 759-764. [71] P. Trang, P.P. Medina, J.F. Wiggins, L. Ruffino, K. Kelnar, M. Omotola, R. Homer, D. Brown, A.G. Bader, J.B. Weidhaas, F.J. Slack, Regression of murine lung tumors by the let-7 microRNA, Oncogene 29 (2010) 1580-1587. [72] M.S. Kumar, S.J. Erkeland, R.E. Pester, C.Y. Chen, M.S. Ebert, P.A. Sharp, T. Jacks, Suppression of non-small cell lung tumor development by the let-7 microRNA family, Proc Natl Acad Sci U S A 105 (2008) 3903-3908. [73] K. Nabeshima, H. Iwasaki, K. Koga, H. Hojo, J. Suzumiya, M. Kikuchi, Emmprin (basigin/CD147): matrix metalloproteinase modulator and multifunctional cell recognition molecule that plays a critical role in cancer progression, Pathol Int 56 (2006) 359-367. [74] F. Kimura, K. Takakura, K. Takebayashi, H. Ishikawa, K. Kasahara, S. Goto, Y. Noda, Messenger ribonucleic acid for the mouse decidual prolactin is present and induced during in vitro decidualization of endometrial stromal cells, Gynecol Endocrinol 15 (2001) 426-432. [75] A.N. Silahtaroglu, D. Nolting, L. Dyrskjot, E. Berezikov, M. Moller, N. Tommerup, S. Kauppinen, Detection of microRNAs in frozen tissue sections by fluorescence in situ hybridization using locked nucleic acid probes and tyramide signal amplification, Nat Protoc 2 (2007) 2520-2528. [76] L. Wang, G. Wu, L. Yu, J. Yuan, F. Fang, Z. Zhai, F. Wang, H. Wang, Inhibition of CD147 expression reduces tumor cell invasion in human prostate cancer cell line via RNA interference, Cancer Biol Ther 5 (2006) 608-614. [77] B. Lane, W. Oxberry, J. Mazella, L. Tseng, Decidualization of human endometrial stromal cells in vitro: effects of progestin and relaxin on the ultrastructure and production of decidual secretory proteins, Hum Reprod 9 (1994) 259-266. [78] V.B. Sampson, N.H. Rong, J. Han, Q. Yang, V. Aris, P. Soteropoulos, N.J. Petrelli, S.P. Dunn, L.J. Krueger, MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells, Cancer Res 67 (2007) 9762-9770. [79] B.C. Paria, J. Reese, S.K. Das, S.K. Dey, Deciphering the cross-talk of implantation: advances and challenges, Science 296 (2002) 2185-2188. [80] K. Red-Horse, Y. Zhou, O. Genbacev, A. Prakobphol, R. Foulk, M. McMaster, S.J. Fisher, Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface, J Clin Invest 114 (2004) 744-754. [81] T. Kurita, R. Medina, A.B. Schabel, P. Young, P. Gama, T.V. Parekh, J. Brody, G.R. Cunha, K.G. Osteen, K.L. Bruner-Tran, L.I. Gold, The activation function-1 domain of estrogen receptor alpha in uterine stromal cells is required for mouse but not human uterine epithelial response to estrogen, Differentiation 73 (2005) 313-322. [82] Y.Y. Ma, Y. Fan, M.K. Bai, J.H. Zhang, Y.P. He, L.L. Yu, L.M. Yue, [The progesterone-induced expression of cyclin G1 and its effect on the proliferation of mouse uterine epithelial cells.], Sheng Li Xue Bao 60 (2008) 541-546. [83] T.E. Spencer, F.W. Bazer, Biology of progesterone action during pregnancy recognition and maintenance of pregnancy, Front Biosci 7 (2002) d1879-1898. [84] T. Toloubeydokhti, Q. Pan, X. Luo, O. Bukulmez, N. Chegini, The expression and ovarian steroid regulation of endometrial micro-RNAs, Reprod Sci 15 (2008) 993-1001. [85] C.D. Johnson, A. Esquela-Kerscher, G. Stefani, M. Byrom, K. Kelnar, D. Ovcharenko, M. Wilson, X. Wang, J. Shelton, J. Shingara, L. Chin, D. Brown, F.J. Slack, The let-7 microRNA represses cell proliferation pathways in human cells, Cancer Res 67 (2007) 7713-7722. [86] K.Y. Lee, F.J. DeMayo, Animal models of implantation, Reproduction 128 (2004) 679-695. [87] H. Lim, L. Ma, W.G. Ma, R.L. Maas, S.K. Dey, Hoxa-10 regulates uterine stromal cell responsiveness to progesterone during implantation and decidualization in the mouse, Mol Endocrinol 13 (1999) 1005-1017. [88] T.Y. Fu, Chang, C.C., Lin, C.T., Peng, S.Y., Ko, Y.J., Tang, P.C., Let-7b-mediated suppression of basigin expression and metastasis in mouse melanoma cells. , experimental cell research (2010). [89] C.M. Alexander, E.J. Hansell, O. Behrendtsen, M.L. Flannery, N.S. Kishnani, S.P. Hawkes, Z. Werb, Expression and function of matrix metalloproteinases and their inhibitors at the maternal-embryonic boundary during mouse embryo implantation, Development 122 (1996) 1723-1736. [90] D.R. Kirby, Development of mouse eggs beneath the kidney capsule, Nature 187 (1960) 707-708. [91] S. Caudroy, M. Polette, B. Nawrocki-Raby, J. Cao, B.P. Toole, S. Zucker, P. Birembaut, EMMPRIN-mediated MMP regulation in tumor and endothelial cells, Clin Exp Metastasis 19 (2002) 697-702. [92] S. Zucker, M. Hymowitz, E.E. Rollo, R. Mann, C.E. Conner, J. Cao, H.D. Foda, D.C. Tompkins, B.P. Toole, Tumorigenic potential of extracellular matrix metalloproteinase inducer, Am J Pathol 158 (2001) 1921-1928. [93] L. Ma, R.A. Weinberg, Micromanagers of malignancy: role of microRNAs in regulating metastasis, Trends Genet 24 (2008) 448-456. [94] S.A. Ciafre, S. Galardi, A. Mangiola, M. Ferracin, C.G. Liu, G. Sabatino, M. Negrini, G. Maira, C.M. Croce, M.G. Farace, Extensive modulation of a set of microRNAs in primary glioblastoma, Biochem Biophys Res Commun 334 (2005) 1351-1358. [95] Q. Huang, K. Gumireddy, M. Schrier, C. le Sage, R. Nagel, S. Nair, D.A. Egan, A. Li, G. Huang, A.J. Klein-Szanto, P.A. Gimotty, D. Katsaros, G. Coukos, L. Zhang, E. Pure, R. Agami, The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis, Nat Cell Biol 10 (2008) 202-210. [96] S. Zhu, H. Wu, F. Wu, D. Nie, S. Sheng, Y.Y. Mo, MicroRNA-21 targets tumor suppressor genes in invasion and metastasis, Cell Res 18 (2008) 350-359. [97] H. Wu, S. Zhu, Y.Y. Mo, Suppression of cell growth and invasion by miR-205 in breast cancer, Cell Res 19 (2009) 439-448. [98] S.F. Tavazoie, C. Alarcon, T. Oskarsson, D. Padua, Q. Wang, P.D. Bos, W.L. Gerald, J. Massague, Endogenous human microRNAs that suppress breast cancer metastasis, Nature 451 (2008) 147-152. [99] H. Xia, Y. Qi, S.S. Ng, X. Chen, D. Li, S. Chen, R. Ge, S. Jiang, G. Li, Y. Chen, M.L. He, H.F. Kung, L. Lai, M.C. Lin, microRNA-146b inhibits glioma cell migration and invasion by targeting MMPs, Brain Res 1269 (2009) 158-165. [100] J. Su, X. Chen, T. Kanekura, A CD147-targeting siRNA inhibits the proliferation, invasiveness, and VEGF production of human malignant melanoma cells by down-regulating glycolysis, Cancer Lett 273 (2009) 140-147.
MicroRNAs(miRNAs)為內源性非蛋白質編碼(endogenous nonprotein-coding)之小分子RNAs,其長度約為18-25個核苷酸(nucleotides),已被證實可藉由鹼基配對方式(base-pairing)對基因進行轉錄後調控(post-transcriptional regulation),並參與多種不同的生理過程。Basigin(Bsg)表現於細胞膜上,為一細胞黏附因子,又稱作extracellular matrix metalloproteinase inducer(EMMPRIN)。研究發現,Bsg可表現於癌細胞,當發生腫瘤轉移(metastasis)時,Bsg促使周圍纖維母細胞或腫瘤細胞產生基質金屬蛋白酵素(matix metalloproteinases, MMPs)。依miRGen資料庫分析比對可知,let-7家族均為調控bsg之候選miRNA,其中尤以let-7b互補之程度最高。藉由構築含有bsg 3’UTR之luciferase報導基因載體,將其轉染至具有內源性表現let-7b之小鼠黑色素瘤細胞(B16-F10 cells)中,發現let-7b可直接與bsg 3’UTR結合而達到抑制luciferase表現之效果。以西方吸漬法分析經轉染let-7b之B16-F10 cells,發現可顯著抑制Bsg與MMP-9之表現,同時亦具有抑制腫瘤細胞轉移與生長之功能。此外,亦探討於小鼠懷孕過程中,let-7b於子宮內膜中可能所扮演之角色。let-7b於著床前之內膜上皮細胞中之表現顯著上升,然基質細胞則於懷孕第1日最高,而後顯著下降,於第4日再顯著上升。以寡核苷酸序列LNATM(Locked Nucleic Acid)作為probe進行偵測,可知let-7b表現於懷孕小鼠子宮(第6日至第8日)之著床點。小鼠懷孕期間血液中具高濃度的助孕素(progesterone, P4)與低濃度的雌激素(17β-estradiol, E2),以雌激素、助孕素培養未發身(prepubertal)小鼠之內膜上皮與基質細胞,發現上皮細胞於培養72 h後,P4與E2處理組之let-7b,其表現顯著上升;基質細胞於培養96 h後,以P4處理組表現最高,且可抑制其細胞增生。再者,轉染let-7b於懷孕第7日之內膜基質細胞可抑制其生長,且顯著抑制Bsg與MMP-9之表現。綜合上述,可知let-7b為一腫瘤抑制因子,可抑制細胞增生與Bsg之表現,且於小鼠著床過程可能扮演重要角色。

The endogenous nonprotein coding microRNAs (miRNAs) of 18-25 nucleotides (nt) have been shown to involve in a wide variety of cellular processes as the posttranscriptional regulators by base-pairing to their target mRNAs. Basigin (Bsg), is highly expressed on the cell surface as an adhesion molecule, which is found in the tumor cells and stimulates adjacent fibroblasts or tumor cells to produce matrix metalloproteinases (MMPs). Therefore, Bsg is also called extracellular matrix metalloproteinase inducer (EMMPRIN). In this study, we postulated that Bsg was a potential target of let-7b according to the computer analysis in miRGen database. Based on the result of luciferase assay, we proved that let-7b could interact with the 3'UTR of Bsg directly; The immunoblotting analysis revealed that the protein level of Bsg in mouse melanoma cell line B16-F10 was also down-regulated by let-7b. In addition, let-7b transfected B16-F10 cells displayed an inhibition of both cellular proliferation and colony formation. Furthermore, it was shown that the overexpression of let-7b in B16-F10 cells could reduce lung metastasis. According to real-time RT-PCR analysis, the expression of let-7b in the epithelial cells increased gradually from day 1 to day 4 of pre-implantation stages and reached the highest level on day 4. On the other hand, the highest level of let-7b in the stromal cells was observed on day 1, although the expression was decreased on day 2 and increased significantly on day 4. By in situ hybridization, let-7b was also found to express in the uteri during days 6-8 of pregnancy. The endometrial cells isolated from prepubertal mice were treated with steroid hormones, progesterone (P4), estradiol (E2) and P4 plus E2. After 96 h of culture in the presence of steroid hormones, the expression levels of let-7b were increased in the endometrial cells, although significant differences were only observed after P4 treatment in the stromal cells and after individual E2 and P4 treatments in the epithelial cells. In association with the increased let-7b expression, the cell proliferation slope, measured by MTT assay, significantly decreased in the presence of P4 and P4 plus E2 than that in the groups of non-hormone and E2 treatments during 72-108 h of culture. Results from the transfection of let-7b into the stromal cells isolated from day 4 pregnant mice or prepubertal mice demonstrated that let-7b attenuated the proliferation during the periods of time examined. After transfection of let-7b into mouse stromal cells isolated from day 7 of pregnancy, the expression of Bsg was suppressed, as well as MMP-9. In conclusion, this study clarifies the expression pattern of let-7b in the uterine epithelial and stromal cells during pre-implantation stages in mice, as well as the inhibitory effect of let-7b associated with steroid hormones on stromal cell proliferation and on the expression.
其他識別: U0005-2507201121062800
Appears in Collections:動物科學系

Show full item record

Google ScholarTM


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.