MCPIP1 Exogenous Overexpression Inhibits Pathways Regulating MYCN Oncoprotein Stability in Neuroblastoma

Boratyn, Elżbieta; Nowak, Iwona; Durbas, Małgorzata; Horwacik, Irena; Sawicka, Anna; Rokita, Hanna

doi:10.1002/jcb.25832

Cited by 16 publications

(50 citation statements)

References 51 publications

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“…NDRG2 suppresses renal cell carcinoma proliferation and invasion [ 62 , 63 ]. NDRG2 regulation is complex and involves both N-Myc and MCPIP1 [ 64 ].…”

Section: Resultsmentioning

confidence: 99%

RNA sequencing reveals widespread transcriptome changes in a renal carcinoma cell line

et al. 2018

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We used RNA sequencing (RNA-Seq) technology to investigate changes in the transcriptome profile in the Caki-1 clear cell renal cell carcinoma (ccRCC) cells, which overexpress monocyte chemoattractant protein-induced protein 1 (MCPIP1). RNA-Seq data showed changes in 11.6% and 41.8% of the global transcriptome of Caki-1 cells overexpressing wild-type MCPIP1 or its D141N mutant, respectively. Gene ontology and KEGG pathway functional analyses showed that these transcripts encoded proteins involved in cell cycle progression, protein folding in the endoplasmic reticulum, hypoxia response and cell signalling. We identified 219 downregulated transcripts in MCPIP1-expressing cells that were either unchanged or upregulated in D141N-expressing cells. We validated downregulation of 15 transcripts belonging to different functional pathways by qRT-PCR. The growth and viability of MCPIP1-expressing cells was reduced because of elevated p21Cip1 levels. MCPIP1-expressing cells also showed reduced levels of DDB1 transcript that encodes component of the E3 ubiquitin ligase that degrades p21Cip1. These results demonstrate that MCPIP1 influences the growth and viability of ccRCC cells by increasing or decreasing the transcript levels for proteins involved in cell cycle progression, protein folding, hypoxia response, and cell signaling.

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“…NDRG2 suppresses renal cell carcinoma proliferation and invasion [ 62 , 63 ]. NDRG2 regulation is complex and involves both N-Myc and MCPIP1 [ 64 ].…”

Section: Resultsmentioning

confidence: 99%

RNA sequencing reveals widespread transcriptome changes in a renal carcinoma cell line

et al. 2018

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“…So far, it has been reported that an antitumour therapy involving proteasome inhibitors led to an upregulation of MCPIP1 . The effects of MCPIP1 expression on breast cancer, clear‐cell renal cell carcinoma (ccRCC), and neuroblastoma (NB) cells were also explored. To date, the effects of MCPIP1 activity on the cell cycle have not been thoroughly investigated.…”

Section: Introductionmentioning

confidence: 99%

MCPIP1 overexpression in human neuroblastoma cell lines causes cell‐cycle arrest by G1/S checkpoint block

Boratyn

Nowak

Karnas

et al. 2020

J of Cellular Biochemistry

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Monocyte chemoattractant protein-1-induced protein 1 (MCPIP1) has a multidomain structure, which assures its pleiotropic activity. The physiological functions of this protein include repression of inflammatory processes and the prevention of immune disorders. The influence of MCPIP1 on the cell cycle of cancer cells has not been sufficiently elucidated. A previous study by our group reported that overexpression of MCPIP1 affects the cell viability, inhibits the activation of the phosphoinositide-3 kinase/mammalian target of rapamycin signalling pathway, and reduces the stability of the MYCN oncogene in neuroblastoma (NB) cells.Furthermore, a decrease in expression and phosphorylation levels of cyclindependent kinase (CDK) 1, which has a key role in the M phase of the cell cycle, was observed. On the basis of these previous results, the purpose of our present study was to elucidate the influence of MCPIP1 on the cell cycle of NB cells. It was confirmed that ectopic overexpression of MCPIP1 in two human NB cell lines, KELLY and BE (2)-C, inhibited cell proliferation. Furthermore, flow cytometric analyses and imaging of the cell cycle with a fluorescence ubiquitination cell-cycle indicator test, demonstrated that overexpression of MCPIP1 causes an accumulation of NB cells in the G1 phase of the cell cycle, while the possibility of an increase in G0 phase due to induction of quiescence or senescence was excluded. Additional assessment of the molecular machinery responsible for the transition between the cell-cycle phases confirmed that MCPIP1 overexpression reduced the expression of cyclins A2, B1, D1, D3, E1, and E2 and decreased the phosphorylation of CDK2 and CDK4, as well as retinoblastoma protein. In conclusion, the present results indicated a relevant impact of overexpression of MCPIP1 on the cell cycle, namely a block of the G1/S cell-cycle checkpoint, resulting in arrest of NB cells in the G1 phase. K E Y W O R D S cell cycle, G1/S cell-cycle arrest, MCPIP1, neuroblastoma

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“…Deregulation of miRNA-3613-3p expression in Kelly and BE(2)-C cells with MCPIP1 overexpression, characterized by inhibition of pro-proliferative pathways, suggests its involvement in the regulation of neuroblastoma cell biology. Additionally, it was identified that the overexpression of MCPIP1 protein causes the downregulation of the most potent oncogene in neuroblastoma, MYCN, in two highly tumorigenic cell lines, BE(2)-C and Kelly, as well as inhibition of the Akt/mammalian target of rapamycin signaling pathway (17). Of note, the PANTHER algorithm revealed the potential involvement of miRNA-3613-3p in the regulation of the Akt signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Plasmid vectors used to obtain enforced expression of MCPIP1 protein were as described previously (16). The transfection procedure for Kelly cells was as described in our previous study (17). Overexpression of wild-type or mutated MCPIP1 protein was verified by western blotting.…”

Section: Kelly Cell Transfection With Genetic Constructs Containing Amentioning

confidence: 99%

Exogenous expression of miRNA-3613-3p causes APAF1 downregulation and affects several proteins involved in apoptosis in BE(2)-C human neuroblastoma cells

et al. 2018

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MicroRNAs (miRNAs) are a class of small non‑coding RNAs involved in post‑transcriptional gene regulation. Furthermore, dysregulation of miRNA expression is an important factor in the pathogenesis of neuroblastoma. Our previous study identified that overexpression of monocyte chemoattractant protein‑induced protein 1 protein led to a significant downregulation of a novel miRNA molecule, miRNA‑3613‑3p. In the present study, the potential involvement of miRNA‑3613‑3p in the cell biology of neuroblastoma was investigated. It was identified that the expression of miRNA‑3613‑3p varies among a range of human neuroblastoma cell lines. As the delineation of the functions of a miRNA requires the identification of its target genes, seven putative mRNAs that may be regulated by miRNA‑3613‑3p were selected. Furthermore, it was identified that overexpression of miRNA‑3613‑3p causes significant downregulation of several genes exhibiting tumor suppressive potential [encoding apoptotic protease‑activating factor 1 (APAF1), Dicer, DNA fragmentation factor subunit β, von Hippel‑Lindau protein and neurofibromin 1] in BE(2)‑C human neuroblastoma cells. APAF1 mRNA was the most significantly decreased transcript in the cells with miRNA‑3613‑3p overexpression. In accordance with the aforementioned results, the downregulation of cleaved caspase-9 and lack of activation of executive caspases in BE(2)‑C cells following miRNA‑3613‑3p overexpression was observed. The results of the present study suggest a potential underlying molecular mechanism of apoptosis inhibition via APAF1 downregulation in human neuroblastoma BE(2)‑C cells with miRNA‑3613‑3p overexpression.

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MCPIP1 Exogenous Overexpression Inhibits Pathways Regulating MYCN Oncoprotein Stability in Neuroblastoma

Cited by 16 publications

References 51 publications

RNA sequencing reveals widespread transcriptome changes in a renal carcinoma cell line

RNA sequencing reveals widespread transcriptome changes in a renal carcinoma cell line

MCPIP1 overexpression in human neuroblastoma cell lines causes cell‐cycle arrest by G1/S checkpoint block

Exogenous expression of miRNA-3613-3p causes APAF1 downregulation and affects several proteins involved in apoptosis in BE(2)-C human neuroblastoma cells

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