Circular RNA circTNPO3 Regulates Paclitaxel Resistance of Ovarian Cancer Cells by miR-1299/NEK2 Signaling Pathway

Mol Ther Nucleic Acids. 2020 Sep 4;21:780-791. doi: 10.1016/j.omtn.2020.06.002. Epub 2020 Jun 8.

Abstract

Circular RNAs (circRNAs) were recently reported to be involved in the pathogenesis of ovarian cancer (OC); however, the molecular mechanisms of circRNAs in tumor progression and paclitaxel (PTX) resistance of OC remain largely undetermined. Here, we focused on circTNPO3 (hsa_circ_0001741), which is located on chromosome 7 (chr7): 128655032-128658211 and derived from TNPO3 gene, and thus we termed as circTNPO3. By microarray and qRT-PCR we identified circTNPO3 to be dramatically high expressed in OC samples and correlated with PTX resistance. Functionally, knockdown of circTNPO3 enhanced cell sensitivity to PTX via promoting PTX-induced apoptosis in vitro and in vivo. In mechanism, circTNPO3 acted as a sponge for microRNA-1299 (miR-1299), and NEK2 (NIMA-related kinase 2) was revealed to be target gene of miR-1299. Subsequently, functional assays illustrated that the oncogenic effects of circTNPO3 were attributed to the regulation of miR-1299/NEK2 axis. In conclusion, circTNPO3 contributed to PTX resistance of OC cells at least partly through upregulating NEK2 expression by sponging miR-1299. circTNPO3/miR-1299/NEK2 signaling pathway might play vital roles in the tumorigenesis and chemoresistance of OC.

Keywords: ceRNA; circTNPO3; circular RNA; microRNA; ovarian cancer; paclitaxel resistance.