Abstract
To identify genes that are frequently downregulated in hepatocellular carcinoma (HCC), a panel of putative underexpressed genes was first established by an in-house cDNA macroarray method. Two different assays, semiquantitative RT–PCR combined with Northern analysis and customized cDNA microarray analysis, were used to screen through these genes and the results were compared. Several genes, some with unknown function, were confirmed to be downregulated by both the methods. The effect of a downregulated gene, BMAL2, on cell proliferation was examined. Overexpression of antisense BMAL2 RNA in 293EBNA cells resulted in reduced cell cycle time, increased plating efficiency in soft agar, diminished TNF-α-induced increment of CPP32/caspase-3 activity, and a reduced proportion of cells in the G2 phase with a concomitantly increased proportion of cells in the S phase. In conclusion, by combining three different methods, we have obtained a panel of frequently down regulated genes in HCC, including BMAL2. Antisense overexpression of BMAL2 enhances cell proliferation.
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References
Beasley RP and Hwang LY . (1984). Semin. Liver Dis., 4, 113–121.
Boige V, Laurent-Puig P, Fouchet P, Flejou JF, Monges G, Bedossa P, Bioulac-Sage P, Capron F, Schmitz A, Olschwang S and Thomas G . (1997). Cancer Res., 57, 1986–1990.
Chisari FV, Klopchin K, Moriyama T, Pasquinelli C, Dunsford HA, Sell S, Pinkert CA, Brinster RL and Palmiter RD . (1989). Cell, 59, 1145–1156.
Crews ST, Thomas JB and Goodman CS . (1988). Cell, 52, 143–151.
Di Bisceglie AM . (1997). Hepatology, 26 (3 Suppl 1), 34S–38S.
Elferink CJ, Ge NL and Levine A . (2001). Mol. Pharmacol., 59, 664–673.
Gerber AN and Tapscott SJ . (1996). Mol. Cell. Biol., 16, 3901–3908.
Hambor JE, Hauer CA, Shu HK, Groger RK, Kaplan DR and Tykocinski ML . (1998). Proc. Natl. Acad. Sci. USA, 85, 4010–4014.
Hoffman EC, Reyes H, Chu FF, Sander F, Conley LH, Brooks BA and Hankinson O . (1991). Science, 252, 954–958.
Hogenesch JB, Gu YZ, Moran SM, Shimomura K, Radcliffe LA, Takahashi JS and Bradfield CA . (2000). J. Neurosci., 20, RC83 (1–5).
Hung SC, Kang MS and Kieff E . (2001). Proc. Natl. Acad. Sci. USA, 98, 1865–1870.
Iizuka N, Oka M, Yamada-Okabe H, Mori N, Tamesa T, Okada T, Takemoto N, Tangoku A, Hamada K, Nakayama H, Miyamoto T, Uchimura S and Hamamoto Y . (2002). Cancer Res., 62, 3939–3944.
Ikeda M, Yu W, Hirai M, Ebisawa T, Honma S, Yoshimura K, Honma KI and Nomura M . (2000). Biochem. Biophys. Res. Commun., 275, 493–502.
Kinzler KW and Vogelstein B . (1996). Cell, 87, 159–170.
Kolluri SK, Weiss C, Koff A and Gottlicher M . (1999). Genes Dev., 13, 1742–1753.
Kuida K, Lippke JA, Ku G, Harding MW, Livingston DJ, Su MS and Flavell RA . (1995). Science, 267, 2000–2003.
Kuida K, Zheng TS, Na S, Kuan C, Yang D, Karasuyama H, Rakic P and Flavell RA . (1996). Nature, 384, 368–372.
Kussano N, Shiraishi K, Kubo K, Oga A, Okita K and Sasaki K . (1999). Hepatology, 29, 1858–1862.
Luo X and Sawadogo M . (1996). Proc. Natl. Acad. Sci. USA, 93, 1308–1313.
Marchio A, Meddeb M, Pineau P, Dangiot G, Tiollais P, Bernheim A and Dejean A . (1997). Genes Chromosomes Cancer, 18, 59–65.
Miyasaka Y, Enomoto N, Nagayama K, Izumi N, Marumo F, Watanabe M and Sato C . (2001). Br. J. Cancer, 85, 228–234.
Moriya K, Fujie H, Shintani Y, Yotsuyanagi H, Tsutsumi T, Ishibashi K, Matsuura Y, Kimura S, Miyamura T and Koike K . (1998). Nat. Med., 4, 1065–1067.
Nagai H, Pineau P, Tiollais P, Buendia MA and Dejean A . (1997). Oncogene, 14, 2927–2933.
Norton JD . (2000). J. Cell Sci., 113, 3897–3905.
Okabe H, Satoh S, Kato T, Kitahara O, Yanagawa R, Yamaoka Y, Tsunoda T, Furukawa Y and Nakamura Y . (2001). Cancer Res., 61, 2129–2137.
Okano T, Yamamoto K, Okano K, Hirota T, Kasahara T, Sasaki M, Takanaka Y and Fukada Y . (2001). Genes Cells, 6, 825–836.
Reddy P, Jacquier AC, Abovich N, Peterson G and Rosbash M . (1986). Cell, 46, 53–61.
Scuric Z, Stain SC, Anderson WF and Hwang JJ . (1998). Hepatology, 27, 943–950.
Shirota Y, Kaneko S, Honda M, Kawai HF and Kobayashi K . (2001). Hepatology, 33, 832–840.
Taylor BL and Zhulin IB . (1999). Microbiol. Mol. Biol. Rev., 63, 479–506.
Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM and Bos JL . (1988). N. Engl. J. Med., 319, 525–532.
Wang ZX, Wang HY and Wu MC . (2001). Br. J. Cancer, 85, 1162–1167.
Wu GS, Kar S and Carr BI . (1995). Life Sci., 57, 1077–1085.
Xu XR, Huang J, Xu ZG, Qian BZ, Zhu ZD, Yan Q, Cai T, Zhang X, Xiao HS, Qu J, Liu F, Huang QH, Cheng ZH, Li NG, Du JJ, Hu W, Shen KT, Lu G, Fu G, Zhong M, Xu SH, Gu WY, Huang W, Zhao XT, Hu GX, Gu JR, Chen Z and Han ZG . (2001). Proc. Natl. Acad. Sci. USA, 98, 15089–15094.
Yeh CT, Chiu HT, Chu CM and Liaw YF . (1998). J. Med. Virol., 55, 42–50.
Yeh CT, Lai HY, Chen TC, Chu CM and Liaw YF . (2001). J. Virol., 75, 11017–11024.
Yeh CT, Lu SC, Chu CM and Liaw YF . (1997). J. Gen. Virol., 78, 2761–2770.
Yeh CT, Shen CH, Tai DI, Chu CM and Liaw YF . (2000). Oncogene, 19, 5213–5220.
Yeh CT, Wong SW, Fung YK and Ou JH . (1993). Proc. Natl. Acad. Sci. USA, 90, 6459–6463.
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This work was supported by a grant from the National Science Council, Taiwan (NSC 91-3112-B-182-002).
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Yeh, CT., Lu, SC., Tseng, IC. et al. Antisense overexpression of BMAL2 enhances cell proliferation. Oncogene 22, 5306–5314 (2003). https://doi.org/10.1038/sj.onc.1206674
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DOI: https://doi.org/10.1038/sj.onc.1206674
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