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

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.

Generally, our findings demonstrated that FNDC3B facilitated cell proliferation and invasion via PI3K/mTOR signaling, and further promoted CRC progression. The novel miR-125a-5p/FNDC3B and miR-217/FNDC3B axes might be new targets for CRC prognosis and therapy.

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.

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 on the proliferation and invasion of CRC cells.