Abstract
Background:
Circular RNAs (circRNAs), a novel class of single-stranded, covalently closed non-coding RNA molecules, have been increasingly recognized for their roles in the cellular landscape over the past decade. These molecules are predominantly localized within the cytoplasm of eukaryotic cells and have been implicated in the pathogenesis of a spectrum of cancers. Despite this, the specific contributions of circRNAs to hepatocellular carcinoma (HCC) have yet to be fully delineated.
Methods:
Our research has identified that cyclic RNA0002898 is downregulated in HCC, with its reduced expression correlating with advanced tumor grade and diminished patient survival outcomes. Furthermore, we have demonstrated that the transcription factor forkhead box C2 (FOXC2) regulates the expression of cyclic RNA0002898, and diminished levels of cyclic RNA0002898 in HCC are associated with enhanced tumor cell proliferation, migration, and invasion in vitro. Mechanistic insights revealed that cyclic RNA0002898 could modulate the expression levels of the tumor suppressor a disintegrin and metalloproteinase with thrombospondin motif 5 (ADAMTS5) by antagonizing miR-145, thereby inhibiting angiogenesis and suppressing the growth of HCC cells.
Results:
Our findings collectively elucidate the regulatory role, functional significance, and underlying mechanism of cyclic RNA0002898 in HCC, a previously uncharted relationship. The potential prognostic implications of cyclic RNA0002898 and its therapeutic potential as a target in HCC warrant further investigation.
Keywords:
Angiogenesis; Circular RNA; Hepatocellular carcinoma; Metastasis; MicroRNA; Transcription factors; Tumor growth.