Abstract
Our previous studies demonstrated that Jab1/Csn5 overexpression is correlated with low survival rates in cancer patients, including nasopharyngeal carcinoma (NPC), breast cancer and hepatocellular carcinoma, and contributes to NPC’s resistance to radiotherapy and cisplatin by regulating DNA damage and repair pathways. However, the molecular mechanism by which Jab1/Csn5 expression is upregulated in NPCs has yet to be determined. In the present study, we identified the upstream regulator of Jab1/Csn5 expression and demonstrated its role in intrinsic resistance of NPC cells to treatment with cisplatin. Signal transducer and activator of transcription-3 (Stat3) expression correlates with and contributes to Jab1/Csn5 transcription. Consistently, silencing of Stat3 in tumors reduced Jab1/Csn5 expression, thereby sensitizing NPC cells to cisplatin-induced apoptosis both in vitro and in vivo. Mechanistically, Stat3 transcriptionally regulated Jab1/Csn5. Furthermore, high mRNA expression levels of Stat3 or Jab1 in colon cancer, breast cancer and glioblastoma are associated with significantly shorter survival times from the R2 online database. These findings identify a novel Stat3-Jab1/Csn5 signaling axis in cancer pathogenesis with therapeutic and prognostic relevance.
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Acknowledgements
We thank Dr Kwok-Wai Lo, The Chinese University of Hong Kong for providing EBV-positive NPC cell line C666.1. We thank Markeda Wade in the Department of Scientific Publications at MD Anderson Cancer Center for editing the manuscript. This study was supported by in part by grants from the National Natural Science Foundation of China (81372816), Fundamental Research Funds for the Central Universities (JUSRP115A31), NIH grant R01CA90853, University Cancer Foundation via the Sister Institution Network Fund of The University of Texas MD Anderson Cancer Center and by the NIH award P30CA016672.
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Pan, Y., Wang, S., Su, B. et al. Stat3 contributes to cancer progression by regulating Jab1/Csn5 expression. Oncogene 36, 1069–1079 (2017). https://doi.org/10.1038/onc.2016.271
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DOI: https://doi.org/10.1038/onc.2016.271
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