Cargando…

Colocalization of MID1IP1 and c-Myc is Critically Involved in Liver Cancer Growth via Regulation of Ribosomal Protein L5 and L11 and CNOT2

Though midline1 interacting protein 1 (MID1IP1) was known as one of the glucose-responsive genes regulated by carbohydrate response element binding protein (ChREBP), the underlying mechanisms for its oncogenic role were never explored. Thus, in the present study, the underlying molecular mechanism o...

Descripción completa

Detalles Bibliográficos
Autores principales: Jung, Ji Hoon, Lee, Hyo-Jung, Kim, Ju-Ha, Sim, Deok Yong, Im, Eunji, Kim, Sinae, Chang, Suhwan, Kim, Sung-Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227012/
https://www.ncbi.nlm.nih.gov/pubmed/32316188
http://dx.doi.org/10.3390/cells9040985
_version_ 1783534411685298176
author Jung, Ji Hoon
Lee, Hyo-Jung
Kim, Ju-Ha
Sim, Deok Yong
Im, Eunji
Kim, Sinae
Chang, Suhwan
Kim, Sung-Hoon
author_facet Jung, Ji Hoon
Lee, Hyo-Jung
Kim, Ju-Ha
Sim, Deok Yong
Im, Eunji
Kim, Sinae
Chang, Suhwan
Kim, Sung-Hoon
author_sort Jung, Ji Hoon
collection PubMed
description Though midline1 interacting protein 1 (MID1IP1) was known as one of the glucose-responsive genes regulated by carbohydrate response element binding protein (ChREBP), the underlying mechanisms for its oncogenic role were never explored. Thus, in the present study, the underlying molecular mechanism of MID1P1 was elucidated mainly in HepG2 and Huh7 hepatocellular carcinoma cells (HCCs). MID1IP1 was highly expressed in HepG2, Huh7, SK-Hep1, PLC/PRF5, and immortalized hepatocyte LX-2 cells more than in normal hepatocyte AML-12 cells. MID1IP1 depletion reduced the viability and the number of colonies and also increased sub G1 population and the number of TUNEL-positive cells in HepG2 and Huh7 cells. Consistently, MID1IP1 depletion attenuated pro-poly (ADP-ribose) polymerase (pro-PARP), c-Myc and activated p21, while MID1IP1 overexpression activated c-Myc and reduced p21. Furthermore, MID1IP1 depletion synergistically attenuated c-Myc stability in HepG2 and Huh7 cells. Of note, MID1IP1 depletion upregulated the expression of ribosomal protein L5 or L11, while loss of L5 or L11 rescued c-Myc in MID1IP1 depleted HepG2 and Huh7 cells. Interestingly, tissue array showed that the overexpression of MID1IP1 was colocalized with c-Myc in human HCC tissues, which was verified in HepG2 and Huh7 cells by Immunofluorescence. Notably, depletion of CCR4-NOT2 (CNOT2) with adipogenic activity enhanced the antitumor effect of MID1IP1 depletion to reduce c-Myc, procaspase 3 and pro-PARP in HepG2, Huh7 and HCT116 cells. Overall, these findings provide novel insight that MID1IP1 promotes the growth of liver cancer via colocalization with c-Myc mediated by ribosomal proteins L5 and L11 and CNOT2 as a potent oncogenic molecule.
format Online
Article
Text
id pubmed-7227012
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-72270122020-05-18 Colocalization of MID1IP1 and c-Myc is Critically Involved in Liver Cancer Growth via Regulation of Ribosomal Protein L5 and L11 and CNOT2 Jung, Ji Hoon Lee, Hyo-Jung Kim, Ju-Ha Sim, Deok Yong Im, Eunji Kim, Sinae Chang, Suhwan Kim, Sung-Hoon Cells Article Though midline1 interacting protein 1 (MID1IP1) was known as one of the glucose-responsive genes regulated by carbohydrate response element binding protein (ChREBP), the underlying mechanisms for its oncogenic role were never explored. Thus, in the present study, the underlying molecular mechanism of MID1P1 was elucidated mainly in HepG2 and Huh7 hepatocellular carcinoma cells (HCCs). MID1IP1 was highly expressed in HepG2, Huh7, SK-Hep1, PLC/PRF5, and immortalized hepatocyte LX-2 cells more than in normal hepatocyte AML-12 cells. MID1IP1 depletion reduced the viability and the number of colonies and also increased sub G1 population and the number of TUNEL-positive cells in HepG2 and Huh7 cells. Consistently, MID1IP1 depletion attenuated pro-poly (ADP-ribose) polymerase (pro-PARP), c-Myc and activated p21, while MID1IP1 overexpression activated c-Myc and reduced p21. Furthermore, MID1IP1 depletion synergistically attenuated c-Myc stability in HepG2 and Huh7 cells. Of note, MID1IP1 depletion upregulated the expression of ribosomal protein L5 or L11, while loss of L5 or L11 rescued c-Myc in MID1IP1 depleted HepG2 and Huh7 cells. Interestingly, tissue array showed that the overexpression of MID1IP1 was colocalized with c-Myc in human HCC tissues, which was verified in HepG2 and Huh7 cells by Immunofluorescence. Notably, depletion of CCR4-NOT2 (CNOT2) with adipogenic activity enhanced the antitumor effect of MID1IP1 depletion to reduce c-Myc, procaspase 3 and pro-PARP in HepG2, Huh7 and HCT116 cells. Overall, these findings provide novel insight that MID1IP1 promotes the growth of liver cancer via colocalization with c-Myc mediated by ribosomal proteins L5 and L11 and CNOT2 as a potent oncogenic molecule. MDPI 2020-04-16 /pmc/articles/PMC7227012/ /pubmed/32316188 http://dx.doi.org/10.3390/cells9040985 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jung, Ji Hoon
Lee, Hyo-Jung
Kim, Ju-Ha
Sim, Deok Yong
Im, Eunji
Kim, Sinae
Chang, Suhwan
Kim, Sung-Hoon
Colocalization of MID1IP1 and c-Myc is Critically Involved in Liver Cancer Growth via Regulation of Ribosomal Protein L5 and L11 and CNOT2
title Colocalization of MID1IP1 and c-Myc is Critically Involved in Liver Cancer Growth via Regulation of Ribosomal Protein L5 and L11 and CNOT2
title_full Colocalization of MID1IP1 and c-Myc is Critically Involved in Liver Cancer Growth via Regulation of Ribosomal Protein L5 and L11 and CNOT2
title_fullStr Colocalization of MID1IP1 and c-Myc is Critically Involved in Liver Cancer Growth via Regulation of Ribosomal Protein L5 and L11 and CNOT2
title_full_unstemmed Colocalization of MID1IP1 and c-Myc is Critically Involved in Liver Cancer Growth via Regulation of Ribosomal Protein L5 and L11 and CNOT2
title_short Colocalization of MID1IP1 and c-Myc is Critically Involved in Liver Cancer Growth via Regulation of Ribosomal Protein L5 and L11 and CNOT2
title_sort colocalization of mid1ip1 and c-myc is critically involved in liver cancer growth via regulation of ribosomal protein l5 and l11 and cnot2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227012/
https://www.ncbi.nlm.nih.gov/pubmed/32316188
http://dx.doi.org/10.3390/cells9040985
work_keys_str_mv AT jungjihoon colocalizationofmid1ip1andcmyciscriticallyinvolvedinlivercancergrowthviaregulationofribosomalproteinl5andl11andcnot2
AT leehyojung colocalizationofmid1ip1andcmyciscriticallyinvolvedinlivercancergrowthviaregulationofribosomalproteinl5andl11andcnot2
AT kimjuha colocalizationofmid1ip1andcmyciscriticallyinvolvedinlivercancergrowthviaregulationofribosomalproteinl5andl11andcnot2
AT simdeokyong colocalizationofmid1ip1andcmyciscriticallyinvolvedinlivercancergrowthviaregulationofribosomalproteinl5andl11andcnot2
AT imeunji colocalizationofmid1ip1andcmyciscriticallyinvolvedinlivercancergrowthviaregulationofribosomalproteinl5andl11andcnot2
AT kimsinae colocalizationofmid1ip1andcmyciscriticallyinvolvedinlivercancergrowthviaregulationofribosomalproteinl5andl11andcnot2
AT changsuhwan colocalizationofmid1ip1andcmyciscriticallyinvolvedinlivercancergrowthviaregulationofribosomalproteinl5andl11andcnot2
AT kimsunghoon colocalizationofmid1ip1andcmyciscriticallyinvolvedinlivercancergrowthviaregulationofribosomalproteinl5andl11andcnot2