FNDC3B, Targeted by miR-125a-5p and miR-217, Promotes the Proliferation and Invasion of Colorectal Cancer Cells via PI3K/mTOR Signaling

作者：Yilong Li, Jie Yang, Hengyang Wang, Wei Qiao, Yongfeng Guo, Shengtao Zhang, Yajuan Guo · 发表于：OncoTargets and Therapy · 年份：2020 · DOI：10.2147/ott.s226520 · 被引用次数：48 · 研究领域：Cell Adhesion Molecules Research、Circular RNAs in diseases、MicroRNA in disease regulation

BACKGROUND: Fibronectin type III domain containing 3B (FNDC3B) acts as an oncogene in various cancers, and abnormal expression of FNDC3B has been found in colorectal cancer (CRC). Our study aimed to illustrate the role of FNDC3B in CRC development. METHODS: Through RT-qPCR and western blotting assays, the mRNA and protein expressions of target genes were measured. CCK-8 and MTT methods were used to detect cell proliferation. Invasion ability was determined using Transwell assay. TargetScan platform and luciferase reporter gene assay were performed to predict and validate the bindings between FNDC3B and miR-125a-5p or miR-217. Besides, the expression correlation was measured by Pearson's Correlation analysis. RESULTS: We found that FNDC3B was significantly upregulated in CRC tissues and tumor cell lines, and high expression of FNDC3B predicted a poor survival outcome. The bindings between FNDC3B and miR-125a-5p and miR-217 were respectively at the motifs of CUCAGGG and AUGCAGU. MiR-125a-5p and miR-217 were downregulated in CRC tissues, and both were negatively correlated with FNDC3B expression. Subsequently, the downregulated miR-125a-5p and miR-217 were confirmed as contributors FNDC3B upregulation in CRC. A loss-of-function assay demonstrated that FNDC3B knockdown inhibited the proliferation of CRC cells, while FNDC3B overexpression promoted the proliferation and invasion of tumor cells. Besides, we validated that PI3K/mTOR signaling was involved in the regulation of FNDC3B ...