TY - JOUR
T1 - The roles and mechanism of IFIT5 in bladder cancer epithelial–mesenchymal transition and progression
AU - Huang, Jun
AU - Lo, U. Ging
AU - Wu, Shiqi
AU - Wang, Bin
AU - Pong, Rey Chen
AU - Lai, Chih Ho
AU - Lin, Ho
AU - He, Dalin
AU - Hsieh, Jer Tsong
AU - Wu, Kaijie
N1 - Funding Information:
This study was supported by the National Natural Science Foundation of China (NSFC 81572516 to K.W.), International Science and Technology Cooperation and Exchange Program in Shaanxi Province (2016KW-021 to K.W.) and a research grant from First Affiliated Hospital of Xi’an Jiaotong University (15YB08 to J.H.).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/6/1
Y1 - 2019/6/1
N2 - The prognosis of bladder cancer (BCa) depends on several key factors including anatomical site, tumor grade, and stage. In general, muscle-invasive bladder cancer (MIBC) is associated with higher incidence of distant metastasis compared with Non-muscle-invasive bladder cancer (NMIBC). Treatment outcome of the patients with metastatic BCa has been very poor with ~15% of overall survival rate. Thus, it is apparently important to understand the underlying biology for metastatic progression of BCa. Although epithelial–mesenchymal transition (EMT) has long been implicated in BCa metastasis and treatment resistance, the underlying mechanism is not fully understood. In this study, we have identified that the expression of interferon induced protein with tetratricopeptide repeats 5 (IFIT5) is positively correlated with pathological characteristics, and predicts a poor prognosis of BCa patients. Since the function of IFIT5 in BCa has not yet been characterized, we demonstrate that IFIT5 can induce EMT, promote cell migration and invasion, and increase the expression of ICAM1 in BCa via down-regulation of mature miR-99a. Moreover, ICAM1 is shown as a direct target of miR-99a. Overall, we conclude that IFIT5 is a new oncogene in BCa.
AB - The prognosis of bladder cancer (BCa) depends on several key factors including anatomical site, tumor grade, and stage. In general, muscle-invasive bladder cancer (MIBC) is associated with higher incidence of distant metastasis compared with Non-muscle-invasive bladder cancer (NMIBC). Treatment outcome of the patients with metastatic BCa has been very poor with ~15% of overall survival rate. Thus, it is apparently important to understand the underlying biology for metastatic progression of BCa. Although epithelial–mesenchymal transition (EMT) has long been implicated in BCa metastasis and treatment resistance, the underlying mechanism is not fully understood. In this study, we have identified that the expression of interferon induced protein with tetratricopeptide repeats 5 (IFIT5) is positively correlated with pathological characteristics, and predicts a poor prognosis of BCa patients. Since the function of IFIT5 in BCa has not yet been characterized, we demonstrate that IFIT5 can induce EMT, promote cell migration and invasion, and increase the expression of ICAM1 in BCa via down-regulation of mature miR-99a. Moreover, ICAM1 is shown as a direct target of miR-99a. Overall, we conclude that IFIT5 is a new oncogene in BCa.
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U2 - 10.1038/s41419-019-1669-z
DO - 10.1038/s41419-019-1669-z
M3 - Article
C2 - 31164632
AN - SCOPUS:85066602821
SN - 2041-4889
VL - 10
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 6
M1 - 437
ER -