Browse > Article
http://dx.doi.org/10.1007/s10059-009-0158-0

miR-372 Regulates Cell Cycle and Apoptosis of AGS Human Gastric Cancer Cell Line through Direct Regulation of LATS2  

Cho, Wha Ja (Biomedical Research Center, Ulsan University Hospital, University of Ulsan College of Medicine)
Shin, Jeong Min (Department of Anatomy and Cell Biology, Hanyang University, College of Medicine)
Kim, Jong Soo (Department of Anatomy and Cell Biology, Hanyang University, College of Medicine)
Lee, Man Ryul (Department of Anatomy and Cell Biology, Hanyang University, College of Medicine)
Hong, Ki Sung (Department of Anatomy and Cell Biology, Hanyang University, College of Medicine)
Lee, Jun-Ho (Department of Anatomy and Cell Biology, Hanyang University, College of Medicine)
Koo, Kyoung Hwa (Department of Anatomy and Cell Biology, Hanyang University, College of Medicine)
Park, Jeong Woo (Department of Biological Sciences, University of Ulsan)
Kim, Kye-Seong (Department of Anatomy and Cell Biology, Hanyang University, College of Medicine)
Abstract
Previously, we have reported tissue- and stage-specific expression of miR-372 in human embryonic stem cells and so far, not many reports speculate the function of this microRNA (miRNA). In this study, we screened various human cancer cell lines including gastric cancer cell lines and found first time that miR-372 is expressed only in AGS human gastric adenocarcinoma cell line. Inhibition of miR-372 using antisense miR-372 oligonucleotide (AS-miR-372) suppressed proliferation, arrested the cell cycle at G2/M phase, and increased apoptosis of AGS cells. Furthermore, AS-miR-372 treatment increased expression of LATS2, while over-expression of miR-372 decreased luciferase reporter activity driven by the 3' untranslated region (3' UTR) of LATS2 mRNA. Over-expression of LATS2 induced changes in AGS cells similar to those in AGS cells treated with AS-miR-372. Taken together, these findings demonstrate an oncogenic role for miR-372 in controlling cell growth, cell cycle, and apoptosis through down-regulation of a tumor suppressor gene, LATS2.
Keywords
AGS gastric cancer cell line; apoptosis; cell cycle; $G_2$-M transition; LATS2; miR-372;
Citations & Related Records

Times Cited By Web Of Science : 18  (Related Records In Web of Science)
연도 인용수 순위
  • Reference
1 Volinia, S., Calin, G.A., Liu, C.G., Ambs, S., Cimmino, A., Petrocca, F., Visone, R., Iorio, M., Roldo, C., Ferracin, M., et al. (2006). A microRNA expression signature of human solid tumors defines cancer gene targets. Proc. Natl. Acad. Sci. USA 103, 2257-2261   DOI   ScienceOn
2 Wu, W., Sun, M., Zou, G.M., and Chen, J. (2007). MicroRNA and cancer: Current status and prospective. Int. J. Cancer 120, 953- 960   DOI   ScienceOn
3 Zamore, P.D., and Haley, B. (2005). Ribo-gnome: the big world of small RNAs. Science 309, 1519-1524   DOI   PUBMED   ScienceOn
4 Doree, M., and Galas, S. (1994). The cyclin-dependent protein kinases and the control of cell division. FASEB J. 8, 1114-1121   DOI
5 He, L., and Hannon, G.J. (2004). MicroRNAs: small RNAs with a big role in gene regulation. Nat. Rev. Genet. 5, 522-531   DOI   ScienceOn
6 Ke, H., Pei, J., Ni, Z., Xia, H., Qi, H., Woods, T., Kelekar, A., and Tao, W. (2004). Putative tumor suppressor Lats2 induces apoptosis through downregulation of Bcl-2 and Bcl-x(L). Exp. Cell Res. 298, 329-338   DOI   ScienceOn
7 Lee, R.C., and Ambros, V. (2001). An extensive class of small RNAs in Caenorhabditis elegans. Science 294, 862-864   DOI   PUBMED   ScienceOn
8 Lu, J., Getz, G., Miska, E.A., Alvarez-Saavedra, E., Lamb, J., Peck, D., Sweet-Cordero, A., Ebert, B.L., Mak, R.H., Ferrando, A.A., et al. (2005). MicroRNA expression profiles classify human cancers. Nature 435, 834-838   DOI   ScienceOn
9 Mertens-Talcott, S.U., Chintharlapalli, S., Li, X., and Safe, S. (2007). The oncogenic microRNA-27a targets genes that regulate specificity protein transcription factors and the G2-M checkpoint in MDA-MB-231 breast cancer cells. Cancer Res. 67, 11001- 11011   DOI   ScienceOn
10 Kim, K.S., Kim, J.S., Lee, M.R., Jeong, H.S., and Kim, J. (2009). A study of microRNAs in silico and in vivo: emerging regulators of embryonic stem cells. FEBS J. 276, 2410-2149
11 Card, D.A., Hebbar, P.B., Li, L., Trotter, K.W., Komatsu, Y., Mishina, Y., and Archer, T.K. (2008). Oct4/Sox2-regulated miR-302 targets cyclin D1 in human embryonic stem cells. Mol. Cell. Biol. 28, 6426-6438   DOI   ScienceOn
12 Lee, K.H., Goan, Y.G., Hsiao, M., Lee, C.H., Jian, S.H., Lin, J.T., Chen, Y.L., and Lu, P.J. (2009). MicroRNA-373 (miR-373) posttranscriptionally regulates large tumor suppressor, homolog 2 (LATS2) and stimulates proliferation in human esophageal cancer. Exp. Cell Res. 315, 2529-2538   DOI   ScienceOn
13 Saito, Y., Suzuki, H., and Hibi, T. (2009). The role of microRNAs in gastrointestinal cancers. J. Gastroenterol. 44 (Suppl 19), 18-22   DOI
14 Carleton, M., Cleary, M.A., and Linsley, P.S. (2007). MicroRNAs and cell cycle regulation. Cell Cycle 6, 2127-2132   DOI   PUBMED   ScienceOn
15 Lee, R.C., Feinbaum, R.L., and Ambros, V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843-854   DOI   ScienceOn
16 Takamizawa, J., Konishi, H., Yanagisawa, K., Tomida, S., Osada, H., Endoh, H., Harano, T., Yatabe, Y., Nagino, M., Nimura, Y., et al. (2004). Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 64, 3753-3756   DOI   ScienceOn
17 Cho, W.C. (2007). OncomiRs: the discovery and progress of microRNAs in cancers. Mol. Cancer 6, 60   DOI   ScienceOn
18 O'Donnell, K.A., Wentzel, E.A., Zeller, K.I., Dang, C.V., and Mendell, J.T. (2005). c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435, 839-843   DOI   ScienceOn
19 Bentwich, I., Avniel, A., Karov, Y., Aharonov, R., Gilad, S., Barad, O., Barzilai, A., Einat, P., Einav, U., Meiri, E., et al. (2005). Identification of hundreds of conserved and nonconserved human microRNAs. Nat. Genet. 37, 766-770   DOI   ScienceOn
20 Bartel, D.P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281-297   DOI   PUBMED   ScienceOn
21 Voorhoeve, P.M., le Sage, C., Schrier, M., Gillis, A.J., Stoop, H., Nagel, R., Liu, Y.P., van Duijse, J., Drost, J., Griekspoor, A., et al. (2006). A genetic screen implicates miRNA-372 and miRNA-373 as oncogenes in testicular germ cell tumors. Cell 124, 1169-1181   DOI   ScienceOn
22 Lewis, B.P., Shih, I.H., Jones-Rhoades, M.W., Bartel, D.P., and Burge, C.B. (2003). Prediction of mammalian microRNA targets. Cell 115, 787-798   DOI   ScienceOn
23 Lee, N.S., Kim, J.S., Cho, W.J., Lee, M.R., Steiner, R., Gompers, A., Ling, D., Zhang, J., Strom, P., Behlke, M., et al. (2008). miR- 302b maintains 'stemness' of human embryonal carcinoma cells by post-transcriptional regulation of Cyclin D2 expression. Biochem. Biophys. Res. Commun. 377, 434-440   DOI   ScienceOn
24 Hayashita, Y., Osada, H., Tatematsu, Y., Yamada, H., Yanagisawa, K., Tomida, S., Yatabe, Y., Kawahara, K., Sekido, Y., and Takahashi, T. (2005). A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res. 65, 9628-9632   DOI   ScienceOn
25 Yabuta, N., Fujii, T., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Nishiguchi, H., Endo, Y., Toji, S., Tanaka, H., Nishimune, Y., et al. (2000). Structure, expression, and chromosome mapping of LATS2, a mammalian homologue of the Drosophila tumor suppressor gene lats/warts. Genomics 63, 263-270   DOI   ScienceOn
26 Matsui, Y., Nakano, N., Shao, D., Gao, S., Luo, W., Hong, C., Zhai, P., Holle, E., Yu, X., Yabuta, N., et al. (2008). Lats2 is a negative regulator of myocyte size in the heart. Circ. Res. 103, 1309- 1318   DOI   ScienceOn
27 Suh, M.R., Lee, Y., Kim, J.Y., Kim, S.K., Moon, S.H., Lee, J.Y., Cha, K.Y., Chung, H.M., Yoon, H.S., Moon, S.Y., et al. (2004). Human embryonic stem cells express a unique set of microRNAs. Dev. Biol. 270, 488-498   DOI   ScienceOn
28 Bartek, J., and Lukas, J. (2006). Cell biology. Balancing life-or-death decisions. Science 314, 261-262   DOI   PUBMED   ScienceOn
29 Leung, W.K., Wu, M.S., Kakugawa, Y., Kim, J.J., Yeoh, K.G., Goh, K.L., Wu, K.C., Wu, D.C., Sollano, J., Kachintorn, U., et al. (2008). Screening for gastric cancer in Asia: current evidence and practice. Lancet Oncol. 9, 279-287   DOI   ScienceOn
30 He, L., Thomson, J.M., Hemann, M.T., Hernando-Monge, E., Mu, D., Goodson, S., Powers, S., Cordon-Cardo, C., Lowe, S.W., Hannon, G.J., et al. (2005). A microRNA polycistron as a potential human oncogene. Nature 435, 828-833   DOI   ScienceOn
31 Li, Y., Pei, J., Xia, H., Ke, H., Wang, H., and Tao, W. (2003). Lats2, a putative tumor suppressor, inhibits G1/S transition. Oncogene 22, 4398-4405   DOI   ScienceOn
32 Kamikubo, Y., Takaori-Kondo, A., Uchiyama, T., and Hori, T. (2003). Inhibition of cell growth by conditional expression of kpm, a human homologue of Drosophila warts/lats tumor suppressor. J. Biol. Chem. 278, 17609-17614   DOI   ScienceOn
33 Cimmino, A., Calin, G.A., Fabbri, M., Iorio, M.V., Ferracin, M., Shimizu, M., Wojcik, S.E., Aqeilan, R.I., Zupo, S., Dono, M., et al. (2005). miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc. Natl. Acad. Sci. USA 102, 13944-13949   DOI   ScienceOn