Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 106, Issue -, Pages 217-224Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2018.06.115
Keywords
NPC; TGE-beta/Smad signaling pathway; EMT; SMAD4; miRNA-34a
Funding
- National Natural Science Foundation of China [81672989]
- Jiangsu Clinical Medicine Science and Technology Special Fund [BL2014091]
- Jiangsu Provincial Commission of Health and Family Planning Young Scholars Award [Q201501]
- Medical Young Talent Foundation of Jiangsu Provincial Health Department [QNRC2016648]
- Natural Science Foundation of Jiangsu Province [BK20151019]
Ask authors/readers for more resources
Epithelial-mesenchymal transition (EMT) is considered a prerequisite for tumor invasion and metastasis in many cancers. However, the mechanisms underlying EMT in nasopharyngeal carcinoma (NPC) is largely unknown. In this study, we found that transforming growth factor-beta (TGF-beta), which reportedly promotes EMT in multiple cancers, can trigger EMT and increase the invasive and migratory capacities of NPC cells. Conversely, the downregulation of SMAD4, a vital member of the canonical TGF-beta pathway, reversed the TGF-beta-induced EMT, invasion, and migration. Further experiments revealed that SMAD4 was the target of miRNA-34a, which was downregulated in NPC tissues and suppressed NPC cell metastasis in vivo. miRNA-34a overexpression also antagonized the TGF-beta-induced EMT progression, invasion, and migration through SMAD4 inhibition. However, the restoration of SMAD4 expression rescued the inhibitory effects of miRNA-34a on tumorigenesis. All these results confirmed that miRNA-34a suppressed the TGF-beta-induced EMT, invasion, and migration of NPC cells by directly targeting SMAD4, which indicated the potential of miR-34a as a therapeutic target against NPC.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available