MYC-activated RNA N6-methyladenosine reader IGF2BP3 promotes cell proliferation and metastasis in nasopharyngeal carcinoma

Du, Mengnan; Peng, Yi; Yang, Li; Sun, Wenlu; Zhu, Hongguang; Wu, Jing; Wu, Lirong; He, Xia

doi:10.1038/s41420-022-00844-6

Cited by 41 publications

(32 citation statements)

References 35 publications

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“…Thus, m 6 A readers play important roles in m 6 A writers or erasers-mediated the stability of targets mRNA. Moreover, MYC-activated IGF2BP3 increase m 6 A-modified level of KPNA2, thereby promoting cell proliferation and metastasis nasopharyngeal carcinoma 181 . Alternatively, IGF2BPs also can stabilize mRNAs in an m 6 A-independent manner.…”

Section: The Role Of Igf2bps As M 6 a Reader In Ca...mentioning

confidence: 99%

The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m⁶A readers in cancer

Sun¹,

Cao²,

Du³

et al. 2022

Int. J. Biol. Sci.

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RNA can be modified by over 170 types of distinct chemical modifications, and the most abundant internal modification of mRNA in eukaryotes is N6-methyladenosine (m 6 A). The m 6 A modification accelerates mRNA process, including mRNA splicing, translation, transcript stability, export and decay. m 6 A RNA modification is installed by methyltransferase-like proteins (writers), and potentially removed by demethylases (erasers), and this process is recognized by m 6 A-binding proteins (readers). Notably, alterations of m 6 A-modified proteins (writers, erasers and readers) are involved in the tumorigenesis, progression and metastasis. Importantly, the fate of m 6 A-methylated mRNA is mediated mostly through m 6 A readers, and among these readers, insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) are unique RNA-binding proteins (RBPs) that stabilize their targets mRNA via m 6 A modification. In this review, we update the writers, erasers and readers, and their cross-talks in m 6 A modification, and briefly discuss the oncogenic role of IGF2BPs in cancer. Most importantly, we mainly review the up-to-date knowledges of IGF2BPs (IGF2BP1/2/3) as m 6 A readers in an m 6 A-modified manner in cancer progression.

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Section: The Role Of Igf2bps As M 6 a Reader In Ca...mentioning

confidence: 99%

The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m⁶A readers in cancer

Sun¹,

Cao²,

Du³

et al. 2022

Int. J. Biol. Sci.

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“…As an RNA binding protein, IGF2BP3 was reported to bind mRNA and ncRNAs and regulate target gene functions [40,41]. We therefore identify circRNAs that bound IGF2BP3.…”

Section: Circarid1a Interacts With Igf2bp3 Protein In Gcmentioning

confidence: 99%

CircARID1A binds to IGF2BP3 in gastric cancer and promotes cancer proliferation by forming a circARID1A-IGF2BP3-SLC7A5 RNA–protein ternary complex

Yang

Huang

et al. 2022

J Exp Clin Cancer Res

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Background Gastric cancer (GC) is one of the most common malignant tumors in China. Circular RNAs (circRNAs) are novel non-coding RNAs with important regulatory roles in cancer progression. IGF2BP3 has been found to play oncogenic roles in various cancers including GC, while the exact mechanism of IGF2BP3 is largely unknown. Methods The expression of IGF2BP3 in GC was evaluated by Western Blot and bioinformatics analysis. CircRNA expression profiles were screened via IGF2BP3 RIP-seq in GC. Sanger sequencing, RNase R digestion, nucleo-plasmic separation and RNA-FISH assays were used to detect the existence and expression of circARID1A. RNA ISH assay was employed to test the expression of circARID1A in paraffin-embedded GC tissues. Moreover, the function of circARID1A on cellular proliferation was assessed by CCK-8, plate colony formation, EdU assays and GC xenograft mouse model in vivo. Furthermore, the location or binding of circARID1A, IGF2BP3 protein and SLC7A5 in GC was evaluated by RNA-FISH/IF or RNA pull-down assays. Results We identified a novel circRNA, circARID1A, that can bind to IGF2BP3 protein. CircARID1A was significantly upregulated in GC tissues compared with noncancerous tissues and positively correlated with tumor length, tumor volume, and TNM stage. CircARID1A knockdown inhibited the proliferation of GC cells in vitro and in vivo and circARID1A played an important role in the oncogenic function of IGF2BP3. Mechanistically, circARID1A served as a scaffold to facilitate the interaction between IGF2BP3 and SLC7A5 mRNA, finally increasing SLC7A5 mRNA stability. Additionally, circARID1A was able to directly bind SLC7A5 mRNA through complementary base-pairing and then formed the circARID1A-IGF2BP3-SLC7A5 RNA–protein ternary complex and promoted the proliferation of GC via regulating AKT/mTOR pathway. Conclusions Altogether, our data suggest that circARID1A is involved in the function of IGF2BP3 and GC proliferation, and the circARID1A-IGF2BP3-SLC7A5 axis has the potential to serve as a novel therapeutic target for GC.

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“…The m6A regulators regulated the m6A methylation in MYC, affecting the stability and translation efficiency of MYC, and then regulated the expression of MYC, which was an important mechanism for the occurrence and development of cancers ( Wu et al, 2021 ; Zheng et al, 2022 ). The m6A regulators of METTL3/5, FTO, IGF2BP1/2/3, YTHDF2 ( Einstein et al, 2021 ; Iaiza et al, 2021 ; Yang et al, 2021 ; Chen et al, 2022 ; Du et al, 2022 ; Hu et al, 2022 ; Huang et al, 2022 ; Liu et al, 2022 ; Luo and Lin, 2022 ), and so on had been proven to modulate the mechanism. In our study, compared with the healthy control, MYC mRNA levels were lower in both NAFL and NASH, while no differences were found between NAFL and NASH.…”

Section: Discussionmentioning

confidence: 99%

New roles of N6-methyladenosine methylation system regulating the occurrence of non-alcoholic fatty liver disease with N6-methyladenosine-modified MYC

Cheng

Zhang

et al. 2022

Front. Pharmacol.

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Non-alcoholic fatty liver disease (NAFLD) has become a major chronic disease in contemporary society, affected by N6-methyladenosine (m6A) RNA methylation, one of the most common RNA modifications. Compared with healthy control, m6A RNA methyltransferase 3 (METTL3) and METTL14 increased, while Wilms tumor 1-associated protein (WTAP) and RNA-binding motif protein 15 (RBM15) decreased significantly in NAFLD, and the m6A demethylases fat mass and obesity-associated protein (FTO) elevated. Meanwhile, the m6A binding proteins, YT521-B homology (YTH) domain-containing 1 (YTHDC1), YTHDC2, insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), heterogeneous nuclear ribonucleoprotein C (HNRNPC), and HNRNPA2B1 were decreased, while eukaryotic translation initiation factor 3 subunit H (EIF3H) was increased significantly. All these changes of m6A regulators had significant differences between healthy control and NAFLD, but no differences between the NAFL and NASH group. The expression level of RBM15, HNRNPC, and HNRNPA2B1 were related to body fat index. RBM15, YTHDC2, HNRNPC, HNRNPA2B1, and EIF3H were related to steatosis. Also, KIAA1429 and YTH domain family 1 (YTHDF1) were related to lobular inflammation. Taken together, m6A regulators were involved in the occurrence of NAFLD. More importantly, abnormal MYC was determined as a key link to m6A regulation of NAFLD. The higher MYC mRNA level was accompanied by higher HDL cholesterol and unsaturated fatty acid proportions, as well as lower fat mass, glucose, and transaminase. Taken together, dysregulation of m6A methylation caused steatosis and fibrosis, affecting the occurrence of NAFLD, and MYC might be its potential target.

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MYC-activated RNA N6-methyladenosine reader IGF2BP3 promotes cell proliferation and metastasis in nasopharyngeal carcinoma

Cited by 41 publications

References 35 publications

The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m⁶A readers in cancer

The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m⁶A readers in cancer

CircARID1A binds to IGF2BP3 in gastric cancer and promotes cancer proliferation by forming a circARID1A-IGF2BP3-SLC7A5 RNA–protein ternary complex

New roles of N6-methyladenosine methylation system regulating the occurrence of non-alcoholic fatty liver disease with N6-methyladenosine-modified MYC

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MYC-activated RNA N6-methyladenosine reader IGF2BP3 promotes cell proliferation and metastasis in nasopharyngeal carcinoma

Cited by 41 publications

References 35 publications

The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m6A readers in cancer

The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m6A readers in cancer

CircARID1A binds to IGF2BP3 in gastric cancer and promotes cancer proliferation by forming a circARID1A-IGF2BP3-SLC7A5 RNA–protein ternary complex

New roles of N6-methyladenosine methylation system regulating the occurrence of non-alcoholic fatty liver disease with N6-methyladenosine-modified MYC

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The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m⁶A readers in cancer

The role of Insulin-like growth factor 2 mRNA-binding proteins (IGF2BPs) as m⁶A readers in cancer