The role of N6-methyladenosine (m6A) modification in the regulation of circRNAs

Zhang, Lele; Hou, Chaofeng; Chen, Chen; Guo, Yaxin; Yuan, Weitang; Yin, Dengke; Wang, Zhibin; Sun, Zhenqiang

doi:10.1186/s12943-020-01224-3

Cited by 226 publications

(186 citation statements)

References 111 publications

(171 reference statements)

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“…As a primary component of the m6A methyltransferase complex, KIAA1429 has recently been demonstrated to promote HCC progression [11,12]. More importantly, growing evidence suggested that the biogenesis and function of circRNAs could be regulated by m6A modi cation and m6A regulated-circRNAs may provide potential therapeutic targets [17,18]. In our present work, we identi ed circDLC1 as a novel KIAA1429-regulated circRNA, which was clinically relevant to favorable prognosis of HCC patients.…”

Section: Discussionmentioning

confidence: 63%

“…The main function of circRNAs in tumor is sponging microRNAs (miRNAs), encoding protein or binding protein (14)(15)(16). Interestingly, more recent studies revealed that methyltransferase-like-3 (METTL3), core complex of methyltransferase, is involved in circRNA biogenesis and function by regulating m6A modi cation (17,18). Thus, the speci c roles of KIAA1429 in mediating circRNAs pathway are urgently needed to explore.…”

Section: Introductionmentioning

confidence: 99%

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Circular RNA circDLC1 Inhibits MMP1-Mediated Liver Cancer Progression via Interaction with HuR

Liu

Lan

et al. 2020

Preprint

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Background: N6-methyladenosine (m6A) modification has been demonstrated to be closely related to cancer progression. KIAA1429, a key component of the m6A methyltransferase complex, has recently been reported to promote hepatocellular carcinoma (HCC) progression by regulating the m6A methylation. However, the involvement of circular RNAs (circRNAs) in KIAA1429-mediated HCC progression is still unknown.Methods: RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation sequencing (m6A-seq) were utilized to identify KIAA1429-regulated circRNAs. The effects of circDLC1 on proliferation and metastasis of hepatoma cells were examined in vitro and in vivo. RT-qPCR was used to measure the expression of circDLC1 in HCC tissues and hepatoma cells. RNA FISH, RIP assays and biotin-labeled RNA pull-down were used to investigate the downstream effector of circDLC1. The downstream targets of circDLC1 were identified using RNA-seq.Results: Our data demonstrated that circDLC1 was downregulated in HCC tissues and closely relevant to favorable prognosis. Overexpression of circDLC1 inhibited the proliferation and motility of hepatoma cells in vitro and in vivo, while silencing of circDLC1 played the opposite role. Mechanistic investigations revealed that circDLC1 could bind to RNA-binding protein HuR, which subsequently reduced the interaction between HuR and MMP1 mRNAs, thus inhibited the expression of MMP1, finally contributed to inhibition of HCC progression.Conclusion: Our work suggests that circDLC1, a downstream target of KIAA1429, is a promising prognostic marker for HCC patients, and the circDLC1-HuR-MMP1 axis may serve as a potential therapeutic target for HCC treatment.

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Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Circular RNA circDLC1 Inhibits MMP1-Mediated Liver Cancer Progression via Interaction with HuR

Liu

Lan

et al. 2020

Preprint

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“…Increasing evidence suggests that m6A modification is misregulated in human cancers and may be ideal targets of cancer therapy (Barbieri and Kouzarides, 2020). The m6A modification affects the pathogenesis of multiple diseases and cancers, not only by affecting coding RNAs but also by affecting non-coding RNAs, such as microRNAs, lncRNAs and circRNAs (Fazi and Fatica, 2019;Zhang et al, 2020).…”

Section: M6a Processes and Their Functionsmentioning

confidence: 99%

“…The m6A modification influences the downstream pathways by regulating the fate of an RNA transcript, processing, splicing, degradation, or translation, whether mRNA or non-coding RNA( Fazi and Fatica, 2019 ; Zhang et al, 2020 ). It plays an important role in various biological processes at different levels of the m6A modification of RNA, such as circadian clock ( Fustin et al, 2013 , 2018 ; Zhong et al, 2018 ), DNA damage response ( Xiang et al, 2017 ; Zlotorynski, 2017 ), neural function regulation ( Poeck et al, 2016 ; Zhang F. et al, 2017 ), drosophila sex determination ( Haussmann et al, 2016 ; Poeck et al, 2016 ), and embryonic development ( Kwon et al, 2019 ).…”

Section: M6a Processes and Their Functionsmentioning

confidence: 99%

Regulation of N6-Methyladenosine in the Differentiation of Cancer Stem Cells and Their Fate

Liu

Chen

et al. 2020

Front. Cell Dev. Biol.

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N6-methyladenosine (m6A) is one of the most common internal RNA modifications in eukaryotes. It is a dynamic and reversible process that requires an orchestrated participation of methyltransferase, demethylase, and methylated binding protein. m6A modification can affect RNA degradation, translation, and microRNA processing. m6A plays an important role in the regulation of various processes in living organisms. In addition to being involved in normal physiological processes such as sperm development, immunity, fat differentiation, cell development, and differentiation, it is also involved in tumor progression and stem cell differentiation. Curiously enough, cancer stem cells, a rare group of cells present in malignant tumors, retain the characteristics of stem cells and play an important role in the survival, proliferation, metastasis, and recurrence of cancers. Recently, studies demonstrated that m6A participates in the self-renewal and pluripotent regulation of these stem cells. However, considering that multiple targets of m6A are involved in different physiological processes, the exact role of m6A in cancer progression remains controversial. This article focuses on the mechanism of m6A and its effects on the differentiation of cancer stem cells, to provide a basis for elucidating the tumorigenesis mechanisms and exploring new potential therapeutic approaches.

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“…The circGSK3B was highly expressed in HCC tissues, and positively associated with HCC tumor size and vascular invasion. Most circRNAs are formed in the nucleus, however, m 6 A modification promotes the cytoplasmic output of circRNAs (38). Thus, the regulation mechanism of circGSK3B cytoplasmic output including m 6 A modification needs to be further studied.…”

Section: Discussionmentioning

confidence: 99%

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The role of N6-methyladenosine (m6A) modification in the regulation of circRNAs

Cited by 226 publications

References 111 publications

Circular RNA circDLC1 Inhibits MMP1-Mediated Liver Cancer Progression via Interaction with HuR

Circular RNA circDLC1 Inhibits MMP1-Mediated Liver Cancer Progression via Interaction with HuR

Regulation of N6-Methyladenosine in the Differentiation of Cancer Stem Cells and Their Fate

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