TY - JOUR
T1 - WTAP promotes osteosarcoma tumorigenesis by repressing HMBOX1 expression in an m6A-dependent manner
AU - Chen, Shijie
AU - Li, Yuezhan
AU - Zhi, Shuang
AU - Ding, Zhiyu
AU - Wang, Weiguo
AU - Peng, Yi
AU - Huang, Yan
AU - Zheng, Ruping
AU - Yu, Haiyang
AU - Wang, Jianlong
AU - Hu, Minghua
AU - Miao, Jinglei
AU - Li, Jinsong
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/8/1
Y1 - 2020/8/1
N2 - N6-methyladenosine (m6A) regulators are involved in the progression of various cancers via regulating m6A modification. However, the potential role and mechanism of the m6A modification in osteosarcoma remains obscure. In this study, WTAP was found to be highly expressed in osteosarcoma tissue and it was an independent prognostic factor for overall survival in osteosarcoma. Functionally, WTAP, as an oncogene, was involved in the proliferation and metastasis of osteosarcoma in vitro and vivo. Mechanistically, M6A dot blot, RNA-seq and MeRIP-seq, MeRIP-qRT-PCR and luciferase reporter assays showed that HMBOX1 was identified as the target gene of WTAP, which regulated HMBOX1 stability depending on m6A modification at the 3′UTR of HMBOX1 mRNA. In addition, HMBOX1 expression was downregulated in osteosarcoma and was an independent prognostic factor for overall survival in osteosarcoma patients. Silenced HMBOX1 evidently attenuated shWTAP-mediated suppression on osteosarcoma growth and metastasis in vivo and vitro. Finally, WTAP/HMBOX1 regulated osteosarcoma growth and metastasis via PI3K/AKT pathway. In conclusion, this study demonstrated the critical role of the WTAP-mediated m6A modification in the progression of osteosarcoma, which could provide novel insights into osteosarcoma treatment.
AB - N6-methyladenosine (m6A) regulators are involved in the progression of various cancers via regulating m6A modification. However, the potential role and mechanism of the m6A modification in osteosarcoma remains obscure. In this study, WTAP was found to be highly expressed in osteosarcoma tissue and it was an independent prognostic factor for overall survival in osteosarcoma. Functionally, WTAP, as an oncogene, was involved in the proliferation and metastasis of osteosarcoma in vitro and vivo. Mechanistically, M6A dot blot, RNA-seq and MeRIP-seq, MeRIP-qRT-PCR and luciferase reporter assays showed that HMBOX1 was identified as the target gene of WTAP, which regulated HMBOX1 stability depending on m6A modification at the 3′UTR of HMBOX1 mRNA. In addition, HMBOX1 expression was downregulated in osteosarcoma and was an independent prognostic factor for overall survival in osteosarcoma patients. Silenced HMBOX1 evidently attenuated shWTAP-mediated suppression on osteosarcoma growth and metastasis in vivo and vitro. Finally, WTAP/HMBOX1 regulated osteosarcoma growth and metastasis via PI3K/AKT pathway. In conclusion, this study demonstrated the critical role of the WTAP-mediated m6A modification in the progression of osteosarcoma, which could provide novel insights into osteosarcoma treatment.
UR - https://www.scopus.com/pages/publications/85089580797
U2 - 10.1038/s41419-020-02847-6
DO - 10.1038/s41419-020-02847-6
M3 - 文章
C2 - 32814762
AN - SCOPUS:85089580797
SN - 2041-4889
VL - 11
JO - Cell Death and Disease
JF - Cell Death and Disease
IS - 8
M1 - 659
ER -
