N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) reader IGF2BP2 promotes gastric cancer progression via targeting SIRT1

Zhang, Zili; Xing, Yu; Gao, Wenqing; Yang, Liping; Shi, Junzhong; Song, Weiliang; Li, Tong

doi:10.1080/21655979.2022.2068920

Cited by 18 publications

(11 citation statements)

References 27 publications

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“…IGF2BP1 promotes neuroendocrine tumor proliferation through post-transcriptional enhancement of EZH2 ( 21 ). N6-methyladenosine (m6A) reader IGF2BP2 encourages gastric cancer metastasis by targeting SIRT1 ( 22 ). By modulating SIRT1 in an m6A-dependent manner, the m6A methyltransferase KIAA1429 operates as an oncogenic factor in colorectal cancer ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

METTL7B serves as a prognostic biomarker and promotes metastasis of lung adenocarcinoma cells

Li¹,

Mu²,

Cao³

et al. 2022

Ann Transl Med

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Background To research the correlation between the prognosis of patients suffering from lung adenocarcinoma (LUAD) and methyltransferase like 7B (METTL7B) expression. Methods The Cancer Genome Atlas (TCGA) database was utilized to verify METTL7B expression, and The Human Protein Atlas database was utilized to verify METTL7B expression at the tissue level. The relationship between METTL7B and LUAD prognostic data was then analyzed using the KM-plotter database. The correlation between METTL7B expression and immune cells was demonstrated through the TIMER database. For exploring the possible mechanism of action, gene set enrichment analysis (GSEA) was performed. Finally, the role of METTL7B in the adverse biological events of LUAD was further explored by in vitro experiments such as proliferation and invasion assays. Results As per the TCGA database, METTL7B expression was increased in cancerous tissues compared with paracancerous tissues, and it was mostly located in the cytoplasm. Patients suffering from LUAD who had low METTL7B expression had a relatively better overall survival (OS) and disease-specific survival (DSS) according to the Kaplan-Meier-plotter (KM-plotter) database. METTL7B expression was significantly associated with immune cell infiltration in LUAD patients, as shown by correlation analysis. GSEA revealed that METTL7B may affect the physiological events of LUAD by playing a part in cell cycle regulation. In vitro cytological experiments demonstrated that METTL7B can markedly affect the metastasis of LUAD cells. Conclusions The reduction of METTL7B expression can prolong OS and DSS in LUAD patients. It may be utilized as a novel predictive biomarker of LUAD, and may be associated with immune infiltration of LUAD. Interfering with METTL7B expression can significantly cause inhibition of LUAD by modulating the ability of cells to proliferate and migrate. These results point to a possible target for developing anti-cancer therapies against LUAD.

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Section: Discussionmentioning

confidence: 99%

METTL7B serves as a prognostic biomarker and promotes metastasis of lung adenocarcinoma cells

Li¹,

Mu²,

Cao³

et al. 2022

Ann Transl Med

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“…In the present study, it was revealed that VIM-AS1 was located in both the cytoplasm and the nucleus of prostate cancer cells and could directly interact with the IGF2BP2 protein. Previous studies have demonstrated that IGF2BP2 was both an important RNA-binding protein and an m6A reader (54,55). Numerous studies have indicated that IGF2BP2 could enhance mRNA stability by recognizing m6A modification sites (56,57).…”

Section: Discussionmentioning

confidence: 99%

VIM‑AS1 promotes proliferation and drives enzalutamide resistance in prostate cancer via IGF2BP2‑mediated HMGCS1 mRNA stabilization

et al. 2023

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VIM-AS1, a cancer-specific long non-coding RNA, has been recognized as a pivotal regulator in multiple types of cancer. However, the role of VIM-AS1 in the proliferation and resistance to anti-androgen therapy of LNCaP and C4-2 prostate cancer cells remains to be determined. In the current study, gain-and-loss experiments were used to investigate the effects of VIM-AS on the proliferation and anti-androgen therapy of LNCaP and C4-2 cells. RNA sequencing, RNA pulldown and RNA immunoprecipitation were used to elucidate the underlying mechanism of VIM-AS1 driving prostate progression. It was demonstrated that VIM-AS1 was upregulated in C4-2 cells, an established castration-resistant prostate cancer (CRPC) cell line, compared with in LNCaP cells, an established hormone-sensitive prostate cancer cell line. The present study further demonstrated that VIM-AS1 was positively associated with the clinical stage of prostate cancer. Functionally, overexpression of VIM-AS1 decreased the sensitivity to enzalutamide treatment and enhanced the proliferation of LNCaP cells in vitro, whereas knockdown of VIM-AS1 increased the sensitivity to enzalutamide treatment and reduced the proliferation of C4-2 cells in vitro and in vivo. Mechanistically, 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) was identified as one of the direct downstream targets of VIM-AS1, and VIM-AS1 promoted HMGCS1 expression by enhancing HMGCS1 mRNA stability through a VIM-AS1/insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2)/HMGCS1 RNA-protein complex. Rescue assays indicated that knockdown of HMGCS1 expression ameliorated the increase in proliferation and enzalutamide resistance of prostate cancer cells induced by VIM-AS1 overexpression. Overall, the present study determined the roles and mechanism of the VIM-AS1/IGF2BP2/HMGCS1 axis in regulating proliferation and enzalutamide sensitivity of prostate cancer cells and suggested that VIM-AS1 may serve as a novel therapeutic target for the treatment of patients with CRPC.

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“…The study on colorectal cancer revealed that LncRNA LINRIS enhanced the stability of IGF2BP2, which increased the binding of IGF2BP2 to m 6 A-modified MYC [ 35 ]. Recent studies showed that IGF2BP2 promotes GC progression by targeting IGF1R and SIRT1 mRNAs and found that there are m 6 A modification sites on IGF1R and SIRT1 genes through bioinformatics analysis, so it is speculated that this promotion of IGF2BP2 may be mediated through m 6 A modification [ 36 , 37 ]. However, it is still unknown whether an m 6 A modification on HMGA1 mRNA was absolutely necessary for IGF2BP2 to regulate its expression.…”

Section: Discussionmentioning

confidence: 99%

IGF2BP2 Promotes Epithelial to Mesenchymal Transition and Metastasis through Stabilizing HMGA1 mRNA in Gastric Cancer

Ouyang

Li³

et al. 2022

Cancers

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As an RNA-binding protein, insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is involved in enhancing the progression of a few malignant tumors by recognizing N6-methyladenosine on targeted RNA. However, the specific effects of IGF2BP2 on gastric cancer (GC) and the underlying mechanisms remain unclear. In this study, the expression level of IGF2BP2 was evaluated by analyzing data from a public database and performing immunohistochemical staining with GC specimens. The effect of IGF2BP2 on GC cell metastasis was investigated by Transwell assays and animal studies. RNA immunoprecipitation (RIP) was performed to identify potential mRNA bound to IGF2BP2. The levels of these identified RNAs were measured by RT-PCR, while corresponding proteins were quantified via Western blot. It was revealed that IGF2BP2 expression in GC tissues was significantly upregulated, and its overexpression was significantly associated with worse survival in GC patients. The aberrant expression of IGF2BP2 was demonstrated to promote the invasion and metastasis of GC cells by both in vivo and in vitro experiments. In subsequent experiments, it was then verified that by directly interacting with HMGA1 mRNA, IGF2BP2 augmented its stability and thus increased its expression. The knocking down of IGF2BP2 could significantly decrease the migration and invasion of GC cells, which could be reversed by increasing HMGA1 expression. Additionally, both in vitro and in vivo epithelial–mesenchymal transition (EMT) of GC cells were enhanced by IGF2BP2/HMGA1 axis. In conclusion, it was proven in our study that the IGF2BP2/HMGA1/EMT axis contributed to GC metastasis, suggesting its potential as a novel predictive and therapeutic biomarker for GC.

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N⁶-methyladenosine (m⁶A) reader IGF2BP2 promotes gastric cancer progression via targeting SIRT1

Cited by 18 publications

References 27 publications

METTL7B serves as a prognostic biomarker and promotes metastasis of lung adenocarcinoma cells

METTL7B serves as a prognostic biomarker and promotes metastasis of lung adenocarcinoma cells

VIM‑AS1 promotes proliferation and drives enzalutamide resistance in prostate cancer via IGF2BP2‑mediated HMGCS1 mRNA stabilization

IGF2BP2 Promotes Epithelial to Mesenchymal Transition and Metastasis through Stabilizing HMGA1 mRNA in Gastric Cancer

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N6-methyladenosine (m6A) reader IGF2BP2 promotes gastric cancer progression via targeting SIRT1

Cited by 18 publications

References 27 publications

METTL7B serves as a prognostic biomarker and promotes metastasis of lung adenocarcinoma cells

METTL7B serves as a prognostic biomarker and promotes metastasis of lung adenocarcinoma cells

VIM‑AS1 promotes proliferation and drives enzalutamide resistance in prostate cancer via IGF2BP2‑mediated HMGCS1 mRNA stabilization

IGF2BP2 Promotes Epithelial to Mesenchymal Transition and Metastasis through Stabilizing HMGA1 mRNA in Gastric Cancer

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N⁶-methyladenosine (m⁶A) reader IGF2BP2 promotes gastric cancer progression via targeting SIRT1