Open Access
ARTICLE
Basic Transcription Factor 3 Is Required for Proliferation and Epithelial–Mesenchymal Transition via Regulation of FOXM1 and JAK2/STAT3 Signaling in Gastric Cancer
De-Zhong Zhang*, Bing-He Chen*, Lan-Fang Zhang†, Ming-Kun Cheng‡, Xiang-Jie Fang*, Xin-Jun Wu*
* The Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xinxiang Medical University,
Weihui, Henan, P.R. China
† The Department of Gastrointestinal, The First Affiliated Hospital of Xinxiang Medical University,
Weihui, Henan, P.R. China
‡ ICU, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, P.R. China
Oncology Research 2017, 25(9), 1453-1462. https://doi.org/10.3727/096504017X14886494526344
Abstract
Gastric cancer (GC) is the most common epithelial malignancy worldwide. Basic transcription factor 3 (BTF3)
plays a crucial role in the regulation of various biological processes. We designed experiments to investigate the
molecular mechanism underlying the role of BTF3 in GC cell proliferation and metastasis. We confirmed that
BTF3 expression was decreased in GC tissues and several GC cell lines. Lentivirus-mediated downregulation
of BTF3 reduced cell proliferation, induced S and G
2/M cell cycle arrest, and increased apoptosis. Knockdown
of BTF3 significantly reduced the expression of Forkhead box M1 (FOXM1). Upregulation of FOXM1 significantly inhibited the decrease in cell proliferation due to BTF3 silencing, S and G2/M cell cycle arrest, and
increase in apoptosis. Knockdown of BTF3 decreased Ki-67 and PCNA expression, whereas it increased p27
expression, which was inhibited by upregulation of FOXM1. Knockdown of BTF3 significantly decreased
the ability to invade and migrate. Moreover, knockdown of BTF3 increased E-cadherin expression, whereas
it decreased N-cadherin and ZEB2 expression, indicating a decrease in epithelial–mesenchymal transition
(EMT). Phosphorylation of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3)
was significantly inhibited by knockdown of BTF3. IL-6-stimulated phosphorylation of STAT3 and JAK2
markedly suppressed inhibition of EMT due to BTF3 silencing. Silencing of BTF3 decreased tumor volume
and weight and reduced peritoneal nodules in implanted tumors. Our findings provide a novel understanding
of the mechanism of GC and highlight the important role of BTF3/FOXM1 in tumor growth and BTF3/JAK2/
STAT3 in EMT and metastasis.
Keywords
Cite This Article
APA Style
Zhang, D., Chen, B., Zhang, L., Cheng, M., Fang, X. et al. (2017). Basic transcription factor 3 is required for proliferation and epithelial–mesenchymal transition via regulation of FOXM1 and JAK2/STAT3 signaling in gastric cancer. Oncology Research, 25(9), 1453-1462. https://doi.org/10.3727/096504017X14886494526344
Vancouver Style
Zhang D, Chen B, Zhang L, Cheng M, Fang X, Wu X. Basic transcription factor 3 is required for proliferation and epithelial–mesenchymal transition via regulation of FOXM1 and JAK2/STAT3 signaling in gastric cancer. Oncol Res. 2017;25(9):1453-1462 https://doi.org/10.3727/096504017X14886494526344
IEEE Style
D. Zhang, B. Chen, L. Zhang, M. Cheng, X. Fang, and X. Wu "Basic Transcription Factor 3 Is Required for Proliferation and Epithelial–Mesenchymal Transition via Regulation of FOXM1 and JAK2/STAT3 Signaling in Gastric Cancer," Oncol. Res., vol. 25, no. 9, pp. 1453-1462. 2017. https://doi.org/10.3727/096504017X14886494526344