STAT3 activation regulated circ-STAT3.46 promote expression of IGF1R by sponging of miR-139-5p in human colon cancer

Yaxiang Shi, Xuan Chen, Biao Xi, Yucheng Qin, Lingjuan Sun, Jianhui Hu, Jingxuan Xu, Xiaowen Yu, Jun Ouyang, Ling Wei


Background: Recently the roles of circRNAs were extensively studied within human malignancies. Now we explored a potential regulatory axis consisted of circ-STAT3.46-miR-139-5p-IGF1R in human colon cancer.
Methods: The expression of circ-STAT3.46-miR-139-5p-IGF1R were determined by using real-time PCR in human colon cancer (n=56) and adjacent normal tissues. The relationship between clinical characters and tissue or serum exosome circ-STAT3.46 were studied. The detailed regulation within circ-STAT3.46-miR- 139-5p-IGF1R was verified by in vitro studies.
Results: Aberrant expression of circ-STAT3.46, miR-139-5p, and IGF1R were spotted between colon cancer tissues and control. A significantly negative correlation between circ-STAT3.46 and miR-139-5p were verified within human colon cancer tissues. Expression of circ-STAT3.46 in colon cancer tissue and serum exosome were associated with TMN stage and bad prognosis of post-surgery colon cancer patients. IGF1R was positively correlated to circ-STAT3.46 in human colon cancer tissues. Moreover, the transcription of circ-STAT3.46 was regulated by IGF1/IGF1R/STAT3 signaling. Overexpression of circ-STAT3.46 can decrease miR-139-5p in colon cancer cells, meanwhile, increased miR-139-5p were found in circSTAT3.46 knockdown cells. RNA pull-down assay revealed that circ-STAT3.46 could sponge miR-139-5p, and luciferase reporter assay indicated that miR-139-5p could further downregulate IGF1R transcription by binding to its 3'UTR in human colon cancer cells.
Conclusions: circ-STAT3.46 was regulated by IGF/IGF1R/STAT3 activation, and overexpression of circ- STAT3.46 can up-regulate IGF1R by sponging of miR-139-5p within human colon cancer.