m6A Modification of Long Non-Coding RNA HNF1A-AS1 Facilitates Cell Cycle Progression in Colorectal Cancer via IGF2BP2-Mediated CCND1 mRNA Stabilization

Bian, Yibo; Wang, Yan; Xu, Shiwen; Gao, Zhishuang; Li, Chao; Fan, Zongyao; Ding, Jie; Wang, Ke‐Ming

doi:10.3390/cells11193008

Cited by 23 publications

(12 citation statements)

References 43 publications

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“…Our results revealed DNA methylation as an apparent modifier of angiogenesis by altering transcription and upregulating expression of different angiogenesis regulators. That includes the transcription factors Sox17 , a promotor of endothelial sprouting behavior and differentiation as well VEGFR2 expression in a cell-intrinsic manner, and ETS transcription factors family member Erg , that transactivate genes involved in key endothelial functions like survival, VEGF-angiogenic signaling pathways along with the VEGF receptor Flt1 , [ 59 – 64 ]. Furthermore, altered DNA methylation regulates extracellular matrix remodeling, forming a more proangiogenic matrix by upregulating fibronectin ( Fn1 ) and thrombospondin-4 ( Thbs4 ) expression, and increasing expression of integrin β5, which is responsible for the cell–matrix interaction [ 65 – 67 ].…”

Section: Discussionmentioning

confidence: 99%

Epigenetics and stroke: role of DNA methylation and effect of aging on blood–brain barrier recovery

Phillips

Stamatovic

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et al. 2023

Fluids Barriers CNS

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Incomplete recovery of blood–brain barrier (BBB) function contributes to stroke outcomes. How the BBB recovers after stroke remains largely unknown. Emerging evidence suggests that epigenetic factors play a significant role in regulating post-stroke BBB recovery. This study aimed to evaluate the epigenetic and transcriptional profile of cerebral microvessels after thromboembolic (TE) stroke to define potential causes of limited BBB recovery. RNA-sequencing and reduced representation bisulfite sequencing (RRBS) analyses were performed using microvessels isolated from young (6 months) and old (18 months) mice seven days poststroke compared to age-matched sham controls. DNA methylation profiling of poststroke brain microvessels revealed 11,287 differentially methylated regions (DMR) in old and 9818 DMR in young mice, corresponding to annotated genes. These DMR were enriched in genes encoding cell structural proteins (e.g., cell junction, and cell polarity, actin cytoskeleton, extracellular matrix), transporters and channels (e.g., potassium transmembrane transporter, organic anion and inorganic cation transporters, calcium ion transport), and proteins involved in endothelial cell processes (e.g., angiogenesis/vasculogenesis, cell signaling and transcription regulation). Integrated analysis of methylation and RNA sequencing identified changes in cell junctions (occludin), actin remodeling (ezrin) as well as signaling pathways like Rho GTPase (RhoA and Cdc42ep4). Aging as a hub of aberrant methylation affected BBB recovery processes by profound alterations (hypermethylation and repression) in structural protein expression (e.g., claudin-5) as well as activation of a set of genes involved in endothelial to mesenchymal transformation (e.g., Sox9, Snai1), repression of angiogenesis and epigenetic regulation. These findings revealed that DNA methylation plays an important role in regulating BBB repair after stroke, through regulating processes associated with BBB restoration and prevalently with processes enhancing BBB injury.

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Section: Discussionmentioning

confidence: 99%

Epigenetics and stroke: role of DNA methylation and effect of aging on blood–brain barrier recovery

Phillips

Stamatovic

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et al. 2023

Fluids Barriers CNS

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“…A recent study revealed that METTL3 installed the m6A modification and enhanced lncRNA HNF1A-AS1 transcript stability to increase HNF1A-AS1 expression. Upregulated HNF1A-AS1 increased the level of CCND1 by suppressing PDCD4, sponging miR-93-5p and enhancing IGF2BP2-mediated CCND1 mRNA stabilization, which accelerated CRC cell-cycle progression and reduced cell apoptosis (41). Research has found that METTL3 promotes the cell proliferation and glycolysis of CRC by upregulating oncogenic lncRNA PTTG3P.…”

Section: Effects Of Mettl3 On Crcmentioning

confidence: 99%

m6A modification on the fate of colorectal cancer: functions and mechanisms of cell proliferation and tumorigenesis

et al. 2023

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N6-methyladenosine (m6A) is the most pervasive RNA modification in eukaryotic cells. The dynamic and reversible m6A modification of RNA plays a critical role in the occurrence and progression of tumors by regulating RNA metabolism, including translocation, mRNA stability or decay, pre-mRNA splicing, and lncRNA processing. Numerous studies have shown that m6A modification is involved in the development of various cancers. This review aims to summarize the significant role of m6A modification in the proliferation and tumorigenesis of CRC, as well as the potential of modulating m6A modification for tumor treatment. These findings may offer new therapeutic strategies for clinical implementation of m6A modification in CRC in the near future.

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“…6 Some lncRNAs, including MALAT1, TUG, NEAT1 and HNF1A-AS1, are reported to be dysregulated in CRC, playing a role in regulating the development and progression of intestinal cancer. [7][8][9][10] N6-methyladenosine (m6A) is the most prevalent modification found in eukaryotic RNA. 11 The process of RNA m6A methylation is dynamic and reversible, and involves three types of proteins: methyltransferases, recognition proteins and demethyltransferases.…”

Section: Introductionmentioning

confidence: 99%

“…16,17 Our recent research has shown that HNF1A-AS1 promotes IGF2BP3 recognition of the m6A modification region of CCND1, thereby stabilizing CCND1 and promoting colon cancer cell growth and metastasis. 7 However, the specific functions and molecular mechanisms of most other lncRNAs and IGF2BP1 in CRC are still not fully understood.…”

Section: Introductionmentioning

confidence: 99%

“…The insulin‐like growth factor 2 mRNA‐binding protein (IGF2BP) family, consisting of IGF2BP1, IGF2BP2 and IGF2BP3, has also been identified as m6A “readers.” 15 Unlike YTHDFs, which regulate pre‐mRNA splicing and promote translation, IGF2BP proteins are responsible for target mRNA stability and are involved in various targets such as MYC, KRAS and MDR1 16,17 . Our recent research has shown that HNF1A‐AS1 promotes IGF2BP3 recognition of the m6A modification region of CCND1, thereby stabilizing CCND1 and promoting colon cancer cell growth and metastasis 7 . However, the specific functions and molecular mechanisms of most other lncRNAs and IGF2BP1 in CRC are still not fully understood.…”

Section: Introductionmentioning

confidence: 99%

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Long non‐coding RNA linc00659 promotes tumour progression by regulating FZD6/Wnt/β‐catenin signalling pathway in colorectal cancer via m6A reader IGF2BP1

Xu,

Liu,

Luo

et al. 2023

The Journal of Gene Medicine

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BackgroundAbnormal N6‐methyladenosine (m6A) modification has become a driving factor in tumour development and progression. The linc00659 is abnormally highly expressed in digestive tract tumours and promotes cancer progression, but there is little research on the mechanism of linc00659 and m6A.MethodsThe expression of linc00659 in colorectal cancer (CRC) tissues and cells was assessed by a quantitative real‐time PCR. The proliferative capacity of CRC cells was determined by colony formation, Cell Counting Kit‐8 and 5‐ethynyl‐2 deoxyuridine assays, and the migratory capacity of CRC was determined by wound healing and transwell assays and tube formation. In vivo, a xenograft tumour model was used to detect the effect of linc00659 on tumour growth. The Wnt/β‐catenin signalling pathway and related protein expression levels were measured by western blotting. The binding of linc00659 to insulin‐like growth factor 2 mRNA‐binding protein 1 (IGF2BP1) was assessed by RNA pull‐down and an immunoprecipitation assay. The effect of IGF2BP1 on FZD6 was detected by an RNA stability assay.ResultsThe expression of linc00659 was abnormally elevated in CRC tissues and cells compared to normal colonic tissues and cells. We confirm that linc00659 promotes the growth of CRC cells both in vivo and in vitro. Mechanistically, linc00659 binds to IGF2BP1 and specifically enhances its activity to stabilize the target gene FZD6. Therefore, linc00659 and IGF2BP1 activate the Wnt/β‐catenin signalling pathway, promoting cell proliferation in CRC.ConclusionsOur results show that linc00659 and IGF2BP1 cooperate to promote the stability of the target FZD6 mRNA, thereby facilitating CRC progression, which may represent a potential diagnostic, prognostic and therapeutic target for CRC.

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m6A Modification of Long Non-Coding RNA HNF1A-AS1 Facilitates Cell Cycle Progression in Colorectal Cancer via IGF2BP2-Mediated CCND1 mRNA Stabilization

Cited by 23 publications

References 43 publications

Epigenetics and stroke: role of DNA methylation and effect of aging on blood–brain barrier recovery

Epigenetics and stroke: role of DNA methylation and effect of aging on blood–brain barrier recovery

m6A modification on the fate of colorectal cancer: functions and mechanisms of cell proliferation and tumorigenesis

Long non‐coding RNA linc00659 promotes tumour progression by regulating FZD6/Wnt/β‐catenin signalling pathway in colorectal cancer via m6A reader IGF2BP1

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