ALKBH5/YTHDF2‐mediated m6A modification of circAFF2 enhances radiosensitivity of colorectal cancer by inhibiting Cullin neddylation

Shao, Yingjie; Liu, Zhenhua; Song, Xing; Sun, Rui; Zhou, You; Zhang, Dachuan; Sun, Hongtao; Huang, Junchao; Wu, Chenxi; Gu, Wenjiang; Zheng, Xiao; Jiang, Jingting

doi:10.1002/ctm2.1318

Cited by 20 publications

(3 citation statements)

References 47 publications

(149 reference statements)

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“…It has been shown that circRNAs containing m6A residues can be translated into protein by non-cap-dependent structures [26]. m6Amodified circRNA might be recognized by the YTHDF2 [27], in which the open reading framework (ORF) may be verified for the translational capability of the circRNA. Several effects of the peptide/protein from circRNA translation have been identified [28].…”

Section: Association Of M6a and Ncrnas With Various Liver Diseasesmentioning

confidence: 99%

Circular RNAs, Noncoding RNAs, and N6-methyladenosine Involved in the Development of MAFLD

Nakashima,

Suga,

Ikeda

et al. 2024

ncRNA

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Noncoding RNAs (ncRNAs), including circular RNAs (circRNAs) and N6-methyladenosine (m6A), have been shown to play a critical role in the development of various diseases including obesity and metabolic disorder-associated fatty liver disease (MAFLD). Obesity is a chronic disease caused by excessive fat accumulation in the body, which has recently become more prevalent and is the foremost risk factor for MAFLD. Causes of obesity may involve the interaction of genetic, behavioral, and social factors. m6A RNA methylation might add a novel inspiration for understanding the development of obesity and MAFLD with post-transcriptional regulation of gene expression. In particular, circRNAs, microRNAs (miRNAs), and m6A might be implicated in the progression of MAFLD. Interestingly, m6A modification can modulate the translation, degradation, and other functions of ncRNAs. miRNAs/circRNAs can also modulate m6A modifications by affecting writers, erasers, and readers. In turn, ncRNAs could modulate the expression of m6A regulators in different ways. However, there is limited evidence on how these ncRNAs and m6A interact to affect the promotion of liver diseases. It seems that m6A can occur in DNA, RNA, and proteins that may be associated with several biological properties. This study provides a mechanistic understanding of the association of m6A modification and ncRNAs with liver diseases, especially for MAFLD. Comprehension of the association between m6A modification and ncRNAs may contribute to the development of treatment tactics for MAFLD.

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Section: Association Of M6a and Ncrnas With Various Liver Diseasesmentioning

confidence: 99%

Circular RNAs, Noncoding RNAs, and N6-methyladenosine Involved in the Development of MAFLD

Nakashima,

Suga,

Ikeda

et al. 2024

ncRNA

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“…m 6 A methylation can be induced by radiotherapy. Shao and colleagues reported that IR (4 Gy) significantly increased the m 6 A levels in several colorectal cancer cells, probably due to the reduced m 6 A eraser ALKBH5 after IR ( Shao et al, 2023 ). A recent report noted that IR increases m 6 A reader YTHDF2 in MDSCs both in vitro (4 Gy) and in vivo (one dose of 20 Gy) ( Wang et al, 2022 , 2023a ).…”

Section: The Crucial Signaling Pathways Activated By Ir or Ir+immune ...mentioning

confidence: 99%

Radiotherapy and immunology

Wang,

Lynch,

Pitroda

et al. 2024

Journal of Experimental Medicine

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The majority of cancer patients receive radiotherapy during the course of treatment, delivered with curative intent for local tumor control or as part of a multimodality regimen aimed at eliminating distant metastasis. A major focus of research has been DNA damage; however, in the past two decades, emphasis has shifted to the important role the immune system plays in radiotherapy-induced anti-tumor effects. Radiotherapy reprograms the tumor microenvironment, triggering DNA and RNA sensing cascades that activate innate immunity and ultimately enhance adaptive immunity. In opposition, radiotherapy also induces suppression of anti-tumor immunity, including recruitment of regulatory T cells, myeloid-derived suppressor cells, and suppressive macrophages. The balance of pro- and anti-tumor immunity is regulated in part by radiotherapy-induced chemokines and cytokines. Microbiota can also influence radiotherapy outcomes and is under clinical investigation. Blockade of the PD-1/PD-L1 axis and CTLA-4 has been extensively investigated in combination with radiotherapy; we include a review of clinical trials involving inhibition of these immune checkpoints and radiotherapy.

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“…MLN4924 emerges as a novel radiosensitizer, augmenting the sensitivity of CRC to radiotherapy ( 53 ). In addition, the interaction between circAFF2 and cullin-associated and neddylation-dissociated protein 1 (CAND1) facilitates the binding of CAND1 to cullin5, suppressing cullin5 neddylation and consequently enhancing radiosensitivity in CRC ( 54 ).…”

Section: Overview Of Neddylationmentioning

confidence: 99%

Advancements in colorectal cancer research: Unveiling the cellular and molecular mechanisms of neddylation (Review)

Wang,

Li,

et al. 2024

Int J Oncol

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Neddylation, akin to ubiquitination, represents a post-translational modification of proteins wherein neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) is modified on the substrate protein through a series of reactions. Neddylation plays a pivotal role in the growth and proliferation of animal cells. In colorectal cancer (CRC), it predominantly contributes to the proliferation, metastasis and survival of tumor cells, decreasing overall patient survival. The strategic manipulation of the NEDD8-mediated neddylation pathway holds immense therapeutic promise in terms of the potential to modulate the growth of tumors by regulating diverse biological responses within cancer cells, such as DNA damage response and apoptosis, among others. MLN4924 is an inhibitor of NEDD8, and its combined use with platinum drugs and irinotecan, as well as cycle inhibitors and NEDD activating enzyme inhibitors screened by drug repurposing, has been found to exert promising antitumor effects. The present review summarizes the recent progress made in the understanding of the role of NEDD8 in the advancement of CRC, suggesting that NEDD8 is a promising anti-CRC target.

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ALKBH5/YTHDF2‐mediated m6A modification of circAFF2 enhances radiosensitivity of colorectal cancer by inhibiting Cullin neddylation

Cited by 20 publications

References 47 publications

Circular RNAs, Noncoding RNAs, and N6-methyladenosine Involved in the Development of MAFLD

Circular RNAs, Noncoding RNAs, and N6-methyladenosine Involved in the Development of MAFLD

Radiotherapy and immunology

Advancements in colorectal cancer research: Unveiling the cellular and molecular mechanisms of neddylation (Review)

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