Recent advances in crosstalk between N6-methyladenosine (m6A) modification and circular RNAs in cancer

Huang, Xin; Guo, Haoyu; Wang, Lutong; Yang, Lingkai; Shao, Zhimin; Zhang, Weiyue

doi:10.1016/j.omtn.2022.01.013

Cited by 26 publications

(13 citation statements)

References 73 publications

(112 reference statements)

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“…Our findings are consistent with those of previous studies, indicating the regulatory effect of circRNAs on m6A modifications. [ 49 ] Moreover, m6A‐seq and RNA‐seq identified SOCS2‐mediated activation of the JAK‐STAT signaling pathway by interfering with ALKBH5 expression. Abnormal regulation of the JAK‐STAT pathway participates in the pathogenesis of various malignant tumors.…”

Section: Discussionmentioning

confidence: 99%

Smoking‐Induced M2‐TAMs, via circEML4 in EVs, Promote the Progression of NSCLC through ALKBH5‐Regulated m6A Modification of SOCS2 in NSCLC Cells

et al. 2023

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Lung cancer is a commonly diagnosed disease worldwide, with non-small cell lung cancers (NSCLCs) accounting for ≈ 85% of cases. Cigarette smoke is an environmental exposure promoting progression of NSCLC, but its role is poorly understood. This study reports that smoking-induced accumulation of M2-type tumor-associated macrophages (M2-TAMs) surrounding NSCLC tissues promotes malignancy. Specifically, extracellular vesicles (EVs) from cigarette smoke extract (CSE)-induced M2 macrophages promoted malignancy of NSCLC cells in vitro and in vivo. circEML4 in EVs from CSE-induced M2 macrophages is transported to NSCLC cells, where it reduced the distribution of ALKBH5 in the nucleus by interacting with Human AlkB homolog H5 (ALKBH5), resulting in elevated N6-methyladenosine (m6A) modifications. m6A-seq and RNA-seq revealed suppressor of cytokine signaling 2 (SOCS2)-mediated activation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway by regulating m6A modification of SOCS2 via ALKBH5. Down-regulation of circEML4 in EVs from CSE-induced M2 macrophages reversed EVs-enhanced tumorigenicity and metastasis in NSCLC cells. Furthermore, this study found that smoking patients showed an increase in circEML4-positive M2-TAMs. These results indicate that smoking-induced M2-TAMs via circEML4 in EVs promote the NSCLC progression through ALKBH5-regulated m6A modification of SOCS2. This study also reveals that circEML4 in EVs from TAMs acts as a diagnostic biomarker for NSCLC, especially for patients with smoking history.

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Section: Discussionmentioning

confidence: 99%

Smoking‐Induced M2‐TAMs, via circEML4 in EVs, Promote the Progression of NSCLC through ALKBH5‐Regulated m6A Modification of SOCS2 in NSCLC Cells

et al. 2023

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“…m6 A plays a crucial role in regulation of circle RNA [ 32 ]. We predicted m6 A sites of circ-CCT3, and RNA immunoprecipitation showed that ALKBH5 and METTL3 can bind to circ-CCT3.…”

Section: Discussionmentioning

confidence: 99%

m ⁶ A-modification regulated circ-CCT3 acts as the sponge of miR-378a-3p to promote hepatocellular carcinoma progression

Liu

Jiang

et al. 2023

Epigenetics

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Background: Circular RNA (circRNA) plays a critical role in tumour progression. Circ-CCT3, a particularly abundant circRNA, was proposed to be involved in tumorigenesis. However, the role of circ-CCT3 in hepatocellular carcinoma remains elusive. Methods: Here, circ-CCT3 (a circRNA derived from exons 3, 4 and 5 of the CCT3 gene, hsa_circ_0004680) was identified by circRNA microarray and validated by qRT-PCR. RNA immunoprecipitation (RIP) was performed to confirm the binding between ALKBH5 along with METTL3 and circ-CCT3. Methylated RNA Immunoprecipitation (MeRIP) was used to detect the N6-methyladenosine (m 2 A) levels of circ-CCT3. CircRNAs in vivo precipitation, luciferase reporter assay, biotin-coupled microRNA capture, and fluorescence in situ hybridization were conducted to assess the interaction between circ-CCT3 and miR-378a-3p. The functions of circ-CCT3 in HCC were evaluated both in vitro and in vivo. Results: We demonstrated that circ-CCT3 was highly expressed in HCC which indicated the poor prognosis. Circ-CCT3 expression served as an independent risk factor for overall survival in patients with HCC. Knocking-down of circ-CCT3 inhibited the proliferation, invasion and migration of HCC cells, and angiogenesis of HUVEC. Mechanistically, ALKBH5 and METTL3 could bind and regulate m A-modification of circ-CCT3. Further, circ-CCT3 upregulated the expression of FLT-1 by sponging miR-378a-3p. Conclusions: Circ-CCT3 was significantly up-regulated in HCC and promoted liver cancer development via miR-378a-3p-FLT1 axis. It was also found that circ-CCT3 was under m A-modification mediated by ALKBH5 and METTL3. Our study highlights circ-CCT3 as a potential therapeutic target of HCC treatment, which provides a novel understanding on mechanisms of circRNAs in HCC progression.

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“…N 6 -methyladenosine (m 6 A) modification can promote the translation of circRNAs into small peptides and this process can be carried out in a way that does not rely on the 5' cap (120). M 6 A modification is an epigenetic modification that widely exists in circRNAs, and plays an important role in regulating gene expression, splicing, RNA editing, RNA stability and controlling mRNA longevity and degradation (121,122). However, most circRNAs originate from the back splicing of exons, which may cause the corresponding mRNA level to decrease.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Emerging landscape of circFNDC3B and its role in human malignancies

et al. 2023

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In recent years, more attention has been paid to expanding the abundance of Circular RNAs (circRNAs), while the circRNAs that have been found to have significant functions have not been studied in different diseases. CircFNDC3B is one of the most researched circRNAs generated from fibronectin type III domain-containing protein 3B (FNDC3B) gene. Accumulating researches have reported the multiple functions of circFNDC3B in different cancer types and other non-neoplastic diseases, and predicted that circFNDC3B might be a potential biomarker. Notably, circFNDC3B can play roles in different diseases by binding to various microRNAs (miRNAs), binding to RNA-binding proteins (RBPs), or encoding functional peptides. This paper systematically summarizes the biogenesis and function of circRNAs, reviews and discusses the roles and molecular mechanisms of circFNDC3B and its target genes in different cancers and non-neoplastic diseases, which will do favor to broaden our comprehension of the function of circRNAs and facilitate subsequent research on circFNDC3B.

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Recent advances in crosstalk between N6-methyladenosine (m6A) modification and circular RNAs in cancer

Cited by 26 publications

References 73 publications

Smoking‐Induced M2‐TAMs, via circEML4 in EVs, Promote the Progression of NSCLC through ALKBH5‐Regulated m6A Modification of SOCS2 in NSCLC Cells

Smoking‐Induced M2‐TAMs, via circEML4 in EVs, Promote the Progression of NSCLC through ALKBH5‐Regulated m6A Modification of SOCS2 in NSCLC Cells

m ⁶ A-modification regulated circ-CCT3 acts as the sponge of miR-378a-3p to promote hepatocellular carcinoma progression

Emerging landscape of circFNDC3B and its role in human malignancies

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Recent advances in crosstalk between N6-methyladenosine (m6A) modification and circular RNAs in cancer

Cited by 26 publications

References 73 publications

Smoking‐Induced M2‐TAMs, via circEML4 in EVs, Promote the Progression of NSCLC through ALKBH5‐Regulated m6A Modification of SOCS2 in NSCLC Cells

Smoking‐Induced M2‐TAMs, via circEML4 in EVs, Promote the Progression of NSCLC through ALKBH5‐Regulated m6A Modification of SOCS2 in NSCLC Cells

m 6 A-modification regulated circ-CCT3 acts as the sponge of miR-378a-3p to promote hepatocellular carcinoma progression

Emerging landscape of circFNDC3B and its role in human malignancies

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m ⁶ A-modification regulated circ-CCT3 acts as the sponge of miR-378a-3p to promote hepatocellular carcinoma progression