The Chromosome 19 microRNA Cluster Facilitates Cancer Stemness in Hepatocellular Carcinoma

19号染色体微RNA簇促进肝细胞癌的干性

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作者:Marian T Underwood ,Varsha Devarapalli ,Goodwin G Jinesh ,John H Lockhart ,Marco Napoli ,Nino Mtchedlidze ,Elsa R Flores ,Andrew S Brohl

Abstract

Background/Objectives: Hepatocellular carcinoma (HCC) is one of the world's deadliest cancers; however, the mechanisms that contribute to its aggressiveness are poorly understood. In the recent literature, overexpression of the Chromosome 19 MicroRNA Cluster (C19MC) has been associated with an aggressive phenotype and unfavorable prognosis in HCC. However, the molecular consequences of C19MC overexpression in HCC remain poorly understood. Methods: Here, we created a constitutive C19MC-overexpressing HCC model and used two different CRISPR-engineered C19MC-overexpressing HCC models to analyze phenotype and transcriptomic changes. Results: We observed that C19MC overexpression induces cancer stem cell (CSC) phenotypic features in vitro and analyzed transcriptomic changes in genes correlating with stemness, such as NFκB and EMT. Conclusions: C19MC induces changes in HCC that are consistent with stemness and aggression, which provides a better understanding of why C19MC could be a biomarker of poor prognosis.

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