Oncotarget

Research Papers:

miR-665 targets c-MYC and HDAC8 to inhibit murine neuroblastoma cell growth

Nagindra Prashad _

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Oncotarget. 2018; 9:33186-33201. https://doi.org/10.18632/oncotarget.26046

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Abstract

Nagindra Prashad1

1Genetics in Medicine, Houston, TX 77054, USA

Correspondence to:

Nagindra Prashad, email: Nagindra.Prashad@gmail.com

Keywords: neuroblastoma; Bt2cAMP; miR-665; c-MYC; HDAC8

Received: November 26, 2017     Accepted: August 13, 2018     Published: September 04, 2018

ABSTRACT

Neuroblastoma is a common tumor of the peripheral nervous system in children. Highly aggressive MYC-driven neuroblastoma is defined by increased c-MYC and/or MYCN expression. This study employed a mouse neuroblastoma cell model to assess the role of miR-665 in tumorigenesis. We found that miR-665 suppresses mRNAs, targeting c-MYC and HDAC8, which are involved in neuroblastoma tumorigenesis. N6,2’-O-dibutyryladenosine 3':5'cyclic monophosphate (Bt2cAMP) inhibited neuroblastoma cell growth by inhibiting c-MYC and HDAC8 expression and activating caspase 3. Bt2cAMP also upregulated miR-665, and miR665 transfection mimicked the effects of Bt2cAMP, including reduced c-MYC and HDAC8 expression, increased caspase 3 activation, and reduced neuroblastoma cell growth. As compared to untreated cells, Bt2cAMP increased the number of cells in G1 phase by 50% and the number in G2-M phase by 5%, while the number of cells in S phase was reduced 2.8-fold. Similarly, miR-665 transfection increased the number of cells in G1 phase by 16% and the number in G2M phase by 2%, and decreased the cells in S-phase by 18%. These findings indicate miR-665 suppresses neuroblastoma tumorigenesis by inhibiting c-MYC and HDAC8 expression and suggest miR-665 has potential as an anti-neuroblastoma therapeutic.


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