RNA N6-methyladenosine reader IGF2BP3 regulates cell cycle and angiogenesis in colon cancer.
Adenosine
/ analogs & derivatives
Animals
Cell Cycle
/ genetics
Cell Proliferation
/ genetics
Colonic Neoplasms
/ genetics
Cyclin D1
/ genetics
DNA Replication
/ genetics
Female
HCT116 Cells
Heterografts
Humans
Male
Methylation
Mice
Neovascularization, Pathologic
/ genetics
RNA Processing, Post-Transcriptional
/ genetics
RNA, Messenger
/ genetics
RNA-Binding Proteins
/ genetics
Vascular Endothelial Growth Factor A
/ genetics
Angiogenesis
Cell cycle
DNA replication
IGF2BP3
N6-Methyladenosine
Journal
Journal of experimental & clinical cancer research : CR
ISSN: 1756-9966
Titre abrégé: J Exp Clin Cancer Res
Pays: England
ID NLM: 8308647
Informations de publication
Date de publication:
29 Sep 2020
29 Sep 2020
Historique:
received:
27
07
2020
accepted:
21
09
2020
entrez:
30
9
2020
pubmed:
1
10
2020
medline:
12
6
2021
Statut:
epublish
Résumé
N6-Methyladenosine (m6A) modification has been implicated in multiple processes for colon cancer development. IGF2BP3 was a newly reported m6A reader, whereas its role in colon cancer remains unclear. The expression of m6A associated enzymes and total m6A level were measured by Western Blotting analysis and m6A RNA Methylation Quantification Kit respectively. Cell cycle was analyzed by flowcytometry. The interaction of IGF2BP3 and related targets was analyzed by RNA immunoprecipitation (RIP) and m6A RNA immunoprecipitation (MeRIP) assays. We investigated all m6A regulated enzymes in colon cancer and found only the overexpression of IGF2BP3 was associated with cancer progression and survival based on The Cancer Genome Atlas (TCGA) databases. Additionally, we also demonstrated IGF2BP3 was associated with DNA replication in the cell cycle. Knockdown of IGF2BP3 significantly repressed percentage of S phase of cell cycle as well as cell proliferation. Further research demonstrated IGF2BP3 bound to the mRNA of Cyclin D1 (CCND1, checkpoint of G1/S phase of cell cycle) and reduced its mRNA stability via reading m6A modification in the CDS region. Overexpression of Cyclin D1 in IGF2BP3 down-regulated cells completely rescued the inhibited percentage of S phase in cell cycle as well as cell proliferation. Additionally, we also demonstrated a similar role of IGF2BP3 at VEGF. IGF2BP3 bound to the mRNA of VEGF and reads m6A modification, thus regulated both expression and stability of VEGF mRNA. Knockdown of IGF2BP3 repressed angiogenesis in colon cancer via regulating VEGF. Knockdown of IGF2BP3 repressed DNA replication in the S phase of cell cycle and angiogenesis via reading m6A modification of CCND1 and VEGF respectively. IGF2BP3 was a possible prognosis marker and potential therapeutic target of colon cancer.
Sections du résumé
BACKGROUND
BACKGROUND
N6-Methyladenosine (m6A) modification has been implicated in multiple processes for colon cancer development. IGF2BP3 was a newly reported m6A reader, whereas its role in colon cancer remains unclear.
METHODS
METHODS
The expression of m6A associated enzymes and total m6A level were measured by Western Blotting analysis and m6A RNA Methylation Quantification Kit respectively. Cell cycle was analyzed by flowcytometry. The interaction of IGF2BP3 and related targets was analyzed by RNA immunoprecipitation (RIP) and m6A RNA immunoprecipitation (MeRIP) assays.
RESULTS
RESULTS
We investigated all m6A regulated enzymes in colon cancer and found only the overexpression of IGF2BP3 was associated with cancer progression and survival based on The Cancer Genome Atlas (TCGA) databases. Additionally, we also demonstrated IGF2BP3 was associated with DNA replication in the cell cycle. Knockdown of IGF2BP3 significantly repressed percentage of S phase of cell cycle as well as cell proliferation. Further research demonstrated IGF2BP3 bound to the mRNA of Cyclin D1 (CCND1, checkpoint of G1/S phase of cell cycle) and reduced its mRNA stability via reading m6A modification in the CDS region. Overexpression of Cyclin D1 in IGF2BP3 down-regulated cells completely rescued the inhibited percentage of S phase in cell cycle as well as cell proliferation. Additionally, we also demonstrated a similar role of IGF2BP3 at VEGF. IGF2BP3 bound to the mRNA of VEGF and reads m6A modification, thus regulated both expression and stability of VEGF mRNA. Knockdown of IGF2BP3 repressed angiogenesis in colon cancer via regulating VEGF.
CONCLUSION
CONCLUSIONS
Knockdown of IGF2BP3 repressed DNA replication in the S phase of cell cycle and angiogenesis via reading m6A modification of CCND1 and VEGF respectively. IGF2BP3 was a possible prognosis marker and potential therapeutic target of colon cancer.
Identifiants
pubmed: 32993738
doi: 10.1186/s13046-020-01714-8
pii: 10.1186/s13046-020-01714-8
pmc: PMC7523351
doi:
Substances chimiques
CCND1 protein, human
0
IGF2BP3 protein, human
0
RNA, Messenger
0
RNA-Binding Proteins
0
VEGFA protein, human
0
Vascular Endothelial Growth Factor A
0
Cyclin D1
136601-57-5
N-methyladenosine
CLE6G00625
Adenosine
K72T3FS567
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
203Subventions
Organisme : Outstanding Clinical Discipline Project of Shanghai Pudong
ID : PWYgy-2018-08
Organisme : Program for Medical Key Departments of Shanghai
ID : ZK2019A10
Organisme : Committee of Shanghai Science and Technology
ID : No.18ZR1433900 and No. 17DZ2200200
Organisme : Specialty Feature Construction Project of Pudong Health and Family Planning Commission of Shanghai
ID : PWZzb2017-15
Organisme : Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling
ID : zdsys202002
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