Circular RNA 101368/miR-200a axis modulates the migration of hepatocellular carcinoma through HMGB1/RAGE signaling.

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Understanding the genomic dysregulations, in particularly non-coding RNA (ncRNA) dysregulations, in HCC may provide novel strategies to HCC treatment. In our previous study, we demonstrated the key role of miR-200a-mediated HMGB1/RAGE signaling in HCC carcinogenesis. In the present study, we identified circular RNA (circRNA)-miRNA pair that might modulate the migration of HCC cell lines based on previously reported GEO database (GSE78520 and GSE43445) and investigated the function and molecular mechanism. circRNA-101368 was predicted by lncTar to target miR-200a, and the expression of circRNA-101368 was significantly upregulated in HCC tissue samples; the overexpression of circRNA-101368 was correlated with poorer prognosis in patients with HCC. Moreover, circRNA-101368 knockdown suppressed the migration and the protein levels of HMGB1, RAGE and NF-κB, while increased the E-Cadherin expression in HCC cell lines. As confirmed by luciferase reporter and RNA immunoprecipitation assays, circRNA-101368 directly bound to miR-200a to negatively regulate each other. The effect of circRNA-101368 knockdown on cell migration and HMGB1/RAGE signaling could be partially attenuated by miR-200a inhibition. In tissue samples, miR-200a was negatively correlated with circRNA-101368 and HMGB1, respectively, whereas circRNA-101368 and HMGB1 was positively correlated. Taken together, we demonstrated a network of circRNAs-miRNA-mRNA in HCC and provided a novel mechanism of HCC cell migration regulation.", "claims": [{"id": "claim-data-access", "statement": "circRNA-101368 was predicted by lncTar to target miR-200a, and the expression of circRNA-101368 was significantly upregulated in HCC tissue samples; the overexpression of circRNA-101368 was correlated with poorer prognosis in patients with HCC.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30265210", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "circRNA-101368 was predicted by lncTar to target miR-200a, and the expression of circRNA-101368 was significantly upregulated in HCC tissue samples; the overexpression of circRNA-101368 was correlated with poorer prognosis in patients with HCC."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Taken together, we demonstrated a network of circRNAs-miRNA-mRNA in HCC and provided a novel mechanism of HCC cell migration regulation.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:30265210", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Taken together, we demonstrated a network of circRNAs-miRNA-mRNA in HCC and provided a novel mechanism of HCC cell migration regulation."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Taken together, we demonstrated a network of circRNAs-miRNA-mRNA in HCC and provided a novel mechanism of HCC cell migration regulation.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:30265210"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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