Unknown

Dataset Information

0

Clinicopathological-Associated Regulatory Network of Deregulated circRNAs in Hepatocellular Carcinoma.


ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide. Here, we present a novel strategy to identify key circRNA signatures of clinically relevant co-expressed circRNA-mRNA networks in pertinent cancer-pathways that modulate prognosis of HCC patients, by integrating clinic-pathological features, circRNA and mRNA expression profiles. Through further integration with miRNA expression profiles, clinically relevant competing-endogenous-RNA (ceRNA) networks of circRNA-miRNA-mRNAs were constructed. At least five clinically relevant nodal-circRNAs, co-expressed with numerous genes, were identified from the circRNA-mRNA networks. These nodal circRNAs upregulated proliferation (except circRaly) and transformation in cells. The most upregulated nodal-circRNA, circGPC3, associated with higher-grade tumors and co-expressed with 33 genes, competes with 11 mRNAs for two shared miRNAs. circGPC3 was experimentally demonstrated to upregulate cell-cycle and migration/invasion in both transformed and non-transformed liver cell-lines. circGPC3 was further shown to act as a sponge of miR-378a-3p to regulate APSM (Abnormal spindle-like microcephaly associated) expression and modulate cell transformation. This study identifies 5 key nodal master circRNAs in a clinically relevant circRNA-centric network that are significantly associated with poorer prognosis of HCC patients and promotes tumorigenesis in cell-lines. The identification and characterization of these key circRNAs in clinically relevant circRNA-mRNA and ceRNA networks may facilitate the design of novel strategies targeting these important regulators for better HCC prognosis.

SUBMITTER: Han J 

PROVIDER: S-EPMC8199648 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC7824949 | biostudies-literature
| S-EPMC5316832 | biostudies-literature
| S-EPMC6010675 | biostudies-literature
| S-EPMC8100808 | biostudies-literature
| S-EPMC9402792 | biostudies-literature
| S-EPMC7836560 | biostudies-literature
| S-EPMC8806338 | biostudies-literature
| S-EPMC7716122 | biostudies-literature
| S-EPMC4674393 | biostudies-literature
| S-EPMC3535701 | biostudies-literature