ADAR2 functions as a tumor suppressor via editing IGFBP7 in esophageal squamous cell carcinoma

  • Authors:
    • Yuan-Bin Chen
    • Xiao-Yu Liao
    • Jiang-Bo Zhang
    • Fang Wang
    • Hai-De Qin
    • Lanjun Zhang
    • Yin Yao Shugart
    • Yi-Xin Zeng
    • Wei-Hua Jia
  • View Affiliations

  • Published online on: December 29, 2016     https://doi.org/10.3892/ijo.2016.3823
  • Pages: 622-630
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Abstract

Esophageal squamous cell carcinoma (ESCC), one of the most aggressive cancers, is characterized by heterogeneous genetic and epigenetic changes. Recently, A-to-I RNA editing, catalyzed by adenosine deaminases acting on RNA (ADARs), was found to be aberrantly regulated during tumorigenesis. We previously reported that ADAR2 was downregulated in ESCC but its role was unclear. Thus, we report here that overexpression of ADAR2 can induce apoptosis in ESCC cell lines and inhibit tumor growth in vitro and in vivo. ADAR2 knockdown inhibited apoptosis in ADAR2 highly expressing tumor cells. RNA-seq assay showed that ADAR2, not ADAR1 or active-site-mutated ADAR2, could edit insulin-like growth factor binding protein 7 (IGFBP7) mRNA in ESCC. IGFBP7 knockdown or ADAR2 catalytic activity destruction abolished the pro-apoptotic function of ADAR2. Mechanistically, RNA editing may stabilize IGFBP7 protein by changing the protease recognition site of matriptase and this is essential for IGFBP7 to induce apoptosis. Western blotting revealed that ADAR2 overexpression could induce IGFBP7-dependent inhibition of Akt signaling. Thus, our data indicate that ADAR2 suppresses tumor growth and induces apoptosis by editing and stabilizing IGFBP7 in ESCC, and this may represent a novel therapeutic target for treating ESCC.
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February-2017
Volume 50 Issue 2

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

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Spandidos Publications style
Chen Y, Liao X, Zhang J, Wang F, Qin H, Zhang L, Shugart YY, Zeng Y and Jia W: ADAR2 functions as a tumor suppressor via editing IGFBP7 in esophageal squamous cell carcinoma. Int J Oncol 50: 622-630, 2017
APA
Chen, Y., Liao, X., Zhang, J., Wang, F., Qin, H., Zhang, L. ... Jia, W. (2017). ADAR2 functions as a tumor suppressor via editing IGFBP7 in esophageal squamous cell carcinoma. International Journal of Oncology, 50, 622-630. https://doi.org/10.3892/ijo.2016.3823
MLA
Chen, Y., Liao, X., Zhang, J., Wang, F., Qin, H., Zhang, L., Shugart, Y. Y., Zeng, Y., Jia, W."ADAR2 functions as a tumor suppressor via editing IGFBP7 in esophageal squamous cell carcinoma". International Journal of Oncology 50.2 (2017): 622-630.
Chicago
Chen, Y., Liao, X., Zhang, J., Wang, F., Qin, H., Zhang, L., Shugart, Y. Y., Zeng, Y., Jia, W."ADAR2 functions as a tumor suppressor via editing IGFBP7 in esophageal squamous cell carcinoma". International Journal of Oncology 50, no. 2 (2017): 622-630. https://doi.org/10.3892/ijo.2016.3823