Identification of a novel oncogene, MMS22L, involved in lung and esophageal carcinogenesis

  • Authors:
    • Minh‑Hue Nguyen
    • Koji Ueda
    • Yusuke Nakamura
    • Yataro Daigo
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  • Published online on: August 10, 2012     https://doi.org/10.3892/ijo.2012.1589
  • Pages: 1285-1296
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Abstract

Genome-wide gene expression profile analyses using a cDNA microarray containing 27,648 genes or expressed sequence tags identified MMS22L (methyl methanesulfonate-sensitivity protein 22-like) to be overexpressed in the majority of clinical lung and esophageal cancers, but not expressed in normal organs except testis. Transfection of siRNAs against MMS22L into cancer cells suppressed its expression and inhibited cell growth, while exogenous expression of MMS22L enhanced the growth of mammalian cells. MMS22L protein was translocated to the nucleus and stabilized by binding to C-terminal portion of NFKBIL2 [nuclear factor of kappa (NFKB) light polypeptide gene enhancer in B-cells inhibitor-like 2]. Expression of a C-terminal portion of NFKBIL2 protein including the MMS22L-interacting site in cancer cells could reduce the levels of MMS22L in nucleus and suppressed cancer cell growth. Interestingly, reduction of MMS22L by siRNAs in cancer cells inhibited the TNF-α-dependent activation of RelA/p65 in the NFKB pathway and expression of its downstream anti-apoptotic molecules such as Bcl-XL and TRAF1. In addition, knockdown of MMS22L expression also enhanced the apoptosis of cancer cells that were exposed to DNA-damaging agents including 5-FU and CDDP. Our data strongly suggest that targeting MMS22L as well as its interaction with NFKBIL2 could be a promising strategy for novel cancer treatments, and also improve the efficacy of DNA damaging anticancer drugs.
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October 2012
Volume 41 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Nguyen MH, Ueda K, Nakamura Y and Daigo Y: Identification of a novel oncogene, MMS22L, involved in lung and esophageal carcinogenesis. Int J Oncol 41: 1285-1296, 2012
APA
Nguyen, M., Ueda, K., Nakamura, Y., & Daigo, Y. (2012). Identification of a novel oncogene, MMS22L, involved in lung and esophageal carcinogenesis. International Journal of Oncology, 41, 1285-1296. https://doi.org/10.3892/ijo.2012.1589
MLA
Nguyen, M., Ueda, K., Nakamura, Y., Daigo, Y."Identification of a novel oncogene, MMS22L, involved in lung and esophageal carcinogenesis". International Journal of Oncology 41.4 (2012): 1285-1296.
Chicago
Nguyen, M., Ueda, K., Nakamura, Y., Daigo, Y."Identification of a novel oncogene, MMS22L, involved in lung and esophageal carcinogenesis". International Journal of Oncology 41, no. 4 (2012): 1285-1296. https://doi.org/10.3892/ijo.2012.1589