Background: In the last decade, a relatively novel, ubiquitous and highly stable subclass of non-coding RNAs, called circular (circ)-RNAs, has increasingly been implicated in cancer development, and several of them have been shown to act as microRNA sponges. As yet, however, the role of circRNAs in lung adenocarcinoma (LUAD) development has largely remained unexplored.
Methods: Bioinformatics, microarray-based and qRT-PCR expression assays were used to assess circRNA, miRNA and mRNA expression in LUAD patient samples and cell lines. siRNA-mediated silencing was used to assess the effect of circCSNK1G3 on various LUAD-associated characteristics such as proliferation, migration, invasion and tumorigenesis, both in vitro and in vivo. Western blotting, immunohistochemistry, fluorescence in situ hybridization (FISH) and luciferase reporter activity assays were used to characterize relationships between circCSNK1G3, miR-143-3p and HOXA10 in LUAD cells.
Results: By screening for differentially expressed circRNAs, we found that circCSNK1G3 was aberrantly expressed in primary LUAD tissues and cell lines. An oncogenic role of circCSNK1G3 was deduced from its aberrant expression and associated enhancement of LUAD A549 and H1299 cell proliferation, migration and invasion. We also found that circCSNK1G3 can directly interact with and suppress miR-143-3p expression by serving as a 'miR-143-3p sponge'. In addition, we found that circCSNK1G3 can modulate homeobox (HOX) A10 expression through miR-143-3p signaling and, thereby, affect LUAD tumorigenesis.
Conclusions: Our data indicate that circCSNK1G3 can induce HOXA10 expression and, thereby, promote the growth and metastasis of LUAD cells through hsa-miR-143-3p sponging. As such, our data highlight the targetability of the circCSNK1G3/miR-143-3p/HOXA10 signaling axis in patients with LUAD. Graphical abstract.
Keywords: Circular RNA; HOXA10; LUAD; circCSNK1G3; miRNA-143-3p.