RT Journal Article
SR Electronic
T1 Preclinical Study: Sunitinib-suppressed MiR-452-5p Facilitates Renal Cancer Cell Invasion and Metastasis Through Modulating SMAD4/SMAD7/EMT Signals
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 286898
DO 10.1101/286898
A1 Saiyang Li
A1 Jin Zhang
A1 Yonghui Chen
A1 Junjie Ma
A1 Wen Kong
A1 Dongkui Gong
A1 Junhua Zheng
A1 Wei Xue
A1 Wei Zhai
A1 Yunfei Xu
YR 2018
UL http://biorxiv.org/content/early/2018/03/22/286898.abstract
AB Although microRNAs (miRNAs) have been revealed as crucial modulators in tumor metastasis and target therapy, our understanding of their roles in metastatic renal cell carcinoma (mRCC) and Sunitinib treatment is limited. Here, We focused on 2 published microarray data to select out our anchored miRNA which was downregulated after Sunitinib treatment while upregulated in metastasis RCC tissues. Then we discovered that treating with Sunitinib, the targeted receptor tyrosine kinase inhibitor (TKI), inhibited renal cell migration and invasion via attenuating the expression of miR-452-5p. The novel identified miR-452-5p was upregulated and associated with poor prognosis in RCC. Preclinical studies using multiple RCC cells and xenografts model illustrated that miR-452-5p could promote RCC cell migration and invasion in vitro and in vivo. Mechanistically, P65 could directly bind to the miR-452-5p promoter and thus transcriptionally induce miR-452-5p expression, which led to post-transcriptionally abrogate SMAD4 expression, thus inhibition of its downstream signals including SMAD7 and EMT (Epithelial-Mesenchymal Transition) associated genes. Our study presented a road map for targeting this newly identified miR-452-5p and its SMAD4/SMAD7/EMT signals pathway, which imparted a new potential therapeutic strategy for mRCC treatment.