microRNA-449a functions as a tumor suppressor in neuroblastoma through inducing cell differentiation and cell cycle arrest

RNA Biology
Zhenze ZhaoLiqin Du

Abstract

microRNA-449a (miR-449a) has been identified to function as a tumor suppressor in several types of cancers. However, the role of miR-449a in neuroblastoma has not been intensively investigated. We recently found that the overexpression of miR-449a significantly induces neuroblastoma cell differentiation, suggesting its potential tumor suppressor function in neuroblastoma. In this study, we further investigated the mechanisms underlying the tumor suppressive function of miR-449a in neuroblastoma. We observed that miR-449a inhibits neuroblastoma cell survival and growth through 2 mechanisms--inducing cell differentiation and cell cycle arrest. Our comprehensive investigations on the dissection of the target genes of miR-449a revealed that 3 novel targets- MFAP4, PKP4 and TSEN15 -play important roles in mediating its differentiation-inducing function. In addition, we further found that its function in inducing cell cycle arrest involves down-regulating its direct targets CDK6 and LEF1. To determine the clinical significance of the miR-449a-mediated tumor suppressive mechanism, we examined the correlation between the expression of these 5 target genes in neuroblastoma tumor specimens and the survival of neuroblastoma patients. Rema...Continue Reading

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Citations

Apr 19, 2016·Biochemical and Biophysical Research Communications·Yinghao LuQian Kang
Jun 10, 2015·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Junqing WangZhenggang Zhu
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Mar 16, 2021·Frontiers in Oncology·Omidvar RezaeiSoudeh Ghafouri-Fard

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Methods Mentioned

BETA
transfection
Assay
gene knockdown
pulldown
pull-down
PCR

Software Mentioned

IPA
FlowJo
NeuroTrack
ImageJ
TreeStar

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