m6A modification-mediated BATF2 acts as a tumor suppressor in gastric cancer through inhibition of ERK signaling
Posted on 2020-07-11 - 16:07
Abstract Background BATF2, also known as SARI, has been implicated in tumor progression. However, its role, underlying mechanisms, and prognostic significance in human gastric cancer (GC) are elusive. Methods We obtained GC tissues and corresponding normal tissues from 8 patients and identified BATF2 as a downregulated gene via RNA-seq. qRT-PCR and western blotting were applied to examine BATF2 levels in normal and GC tissues. The prognostic value of BATF2 was elucidated using tissue microarray and IHC analyses in two independent GC cohorts. The functional roles and mechanistic insights of BATF2 in GC growth and metastasis were evaluated in vitro and in vivo. Results BATF2 expression was significantly decreased in GC tissues at both the mRNA and protein level. Multivariate Cox regression analysis revealed that BATF2 was an independent prognostic factor and effective predictor in patients with GC. Low BATF2 expression was remarkably associated with peritoneal recurrence after curative gastrectomy. Moreover, elevated BATF2 expression effectively suppressed GC growth and metastasis in vitro and in vivo. Mechanistically, BATF2 binds to p53 and enhances its protein stability, thereby inhibiting the phosphorylation of ERK. Tissue microarray results indicated that the prognostic value of BATF2 was dependent on ERK activity. In addition, the N6-methyladenosine (m6A) modification of BATF2 mRNA by METTL3 repressed its expression in GC. Conclusions Collectively, our findings indicate the pivotal role of BATF2 in GC and highlight the regulatory function of the METTL3/BATF2/p53/ERK axis in modulating GC progression, which provides potential prognostic and therapeutic targets for GC treatment.
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Xie, Jian-Wei; Huang, Xiao-Bo; Chen, Qi-Yue; Ma, Yu-Bin; Zhao, Ya-Jun; Liu, Li-Chao; et al. (2020). m6A modification-mediated BATF2 acts as a tumor suppressor in gastric cancer through inhibition of ERK signaling. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.5056643.v1
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AUTHORS (15)
JX
Jian-Wei Xie
XH
Xiao-Bo Huang
QC
Qi-Yue Chen
YM
Yu-Bin Ma
YZ
Ya-Jun Zhao
LL
Li-Chao Liu
JW
Jia-Bin Wang
JL
Jian-Xian Lin
JL
Jun Lu
LC
Long-Long Cao
ML
Mi Lin
RT
Ru-Hong Tu
CZ
Chao-Hui Zheng
CH
Chang-Ming Huang
PL
Ping Li