Circular RNA circNEURL4 inhibits cell proliferation and invasion of papillary thyroid carcinoma by sponging miR-1278 and regulating LATS1 expression

Am J Transl Res. 2021 Jun 15;13(6):5911-5927. eCollection 2021.

Abstract

Circular RNAs (circRNA) are found to be closely associated with cancers as their possibility as "sponges" to miRNAs, thus liberating the downstream target mRNA. However, deep research is still needed to study the function of circRNA in papillary thyroid carcinoma (PTC). Here, we sought to explore new circRNA which could play an important role in the development of PTC. We filtered candidate circRNAs based on microarray data from public database and verified the result using qRT-PCR. We performed CCK8 assay, colony formation assay, apoptosis assay, transwell assays, and xenograft experiments to explore the function of selected circRNA on PTC. We predicted the miRNA targets of the circRNA and the target gene of miRNA through bioinformatic analysis and validated the target by mutant experiments. And by the use of overexpression experiments, knockdown experiments, and the functional assays mentioned above, we figured out the pathway behind the selected circRNA. Based on our data, we found that circNEURL4 was significantly decreased in the PTC samples and lower expression of circNEURL4 was closely associated with a poor prognosis of patients with PTC. Then, we proved that circNEURL4 could inhibit cell proliferation and invasion of PTC in vivo and in vitro. Furthermore, we demonstrated that circNEURL4 may binding to miR-1278 and thus indirectly improving the expression of LATS1. Our findings revealed that circNEURL4 may probably serve as a diagnostic marker to predict PTC patients' prognosis and a possible therapeutic target to PTC via miR-1278/LATS1 axis.

Keywords: LATS1; Papillary thyroid carcinoma; cell invasion; cell proliferation; circNEURL4; miR-278.