MicroRNA-224 Induces G1/S Checkpoint Release in Liver Cancer

Journal of Clinical Medicine
Fangmei AnFlorin M Selaru

Abstract

Profound changes in microRNA (miR) expression levels are frequently found in liver cancers compared to the normal liver. In this study, we evaluate the expression of miR-224 in human HCC and CCA, as well as its downstream targets and affected pathways. We show that miR-224 is upregulated in a large cohort of human CCA, similar to its upregulation in human HCC. For the purpose of studying the roles of miR-224 in HCC and CCA, we enforced miR-224 expression in cells. mRNA arrays followed by Ingenuity Pathway Analysis (IPA)-identified putative molecules and pathways downstream of miR-224. Phenotypically, we report that enforced expression of miR-224 increases the growth rate of normal cholangiocytes, CCA cell lines, and HCC cell lines. In addition, we identified, in an unbiased fashion, that one of the major biologic processes affected by miR-224 is Gap1 (G1) to Synthesis (S) transition checkpoint release. We next identified p21, p15, and CCNE1 as downstream targets of miR-224 and confirmed the coordinated downregulation results in the increased phosphorylation of Retinoblastoma (Rb) with resulting G1/S checkpoint release. Our data suggest that miR-224 is a master regulator of cell cycle progression, and that its overexpression res...Continue Reading

References

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Citations

Aug 3, 2019·Molecular Carcinogenesis·Merricka C LivingstoneJohn D Groopman
Nov 2, 2018·Viruses·Marie-Laure PlissonnierMirjam B Zeisel
Dec 3, 2020·Annual Review of Pathology·Pedro M RodriguesJesus M Banales
Jun 1, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Khadijeh MahboobniaAmirhossein Sahebkar

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Methods Mentioned

BETA
PCR
fluorescence-activated cell sorter
FCS
transfection
Assay
transfections
flow cytometry

Software Mentioned

Cell Quest
TargetScan
Ingenuity Pathway Analysis ( IPA )
Ingenuity Pathway Analysis ( IPA

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