ALYREF mediates RNA m5C modification to promote hepatocellular carcinoma progression

Xue, Chen; Gu, Xinyu; Zheng, Qiuxian; Shi, Qingmiao; Yuan, Xin; Su, Yuanshuai; Jia, Junjun; Jiang, Jianwen; Lu, Juan; Li, Lanjuan

doi:10.1038/s41392-023-01395-7

Cited by 24 publications

(16 citation statements)

References 5 publications

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“…To address the underlying mechanism of the effect of ALYREF on HCC progression, we combined the data from RNA-seq, m 5 C-seq and iCLIP-seq to establish the gene set overlaps to narrow down the scope of downstream targets. Although the previous study has reported the genes which are modi ed by ALYREF-mediated RNA m 5 C modi cation by sequencing [12], but the ALYREF-m 5 C-targets were not fully characterized. So, m 5 Cassociated candidate genes speci cally involved in HCC deserve further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…Bioinformatics analyses have revealed that ALYREF expression was closely associated with the poor prognosis of patients with HCC [11]. A recent study showed that ALYREF mediates RNA m 5 C modi cation to promote hepatocellular carcinoma progression [12]. However, the precise molecular mechanisms of ALYREF-mediated RNA m 5 C modi cation in HCC development are yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

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ALYREF facilitates the proliferation of hepatocellular carcinoma via MAZ-mediated p53-dependent cell cycle promotion

Ma,

Liu,

Rong

et al. 2023

Preprint

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Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, with poor prognosis and high mortality. Increasing evidence suggests that m5C binding protein ALYREF plays an important role in HCC progression. However, further research is required to understand its mechanism.The mechanism of ALYREF in HCC was investigated through combined RNA-seq, m5C-seq, and iCLIP-seq to identify potential target genes. Moreover, RT-qPCR, m5C dot blot assay, RNA immunoprecipitation, methylated RNA immuno-precipitation, dual-luciferase reporter assay, and RNA decay assay were used to confirm the mechanism.We identified 8 candidate genes which are modified by ALYREF-mediated RNA m5C modification. Moreover, we found that the content of MAZ modified by m5C was regulated by the methyltransferase NSUN2, and ALYREF could bind to the m5C site of MAZ mRNA and increase its stability. Additionally, we found that knockdown MAZ could inhibit HCC proliferation and reduce the promoting effect of ALYREF overexpression on HCC cell growth in vitro and in vivo. ALYREF and MAZ have a positive correlation; the higher the expression of ALYREF and MAZ, the lower the overall survival rate. Moreover, MAZ could bind to the p53 promoter and suppress the expression of p53, then mediate cell cycle promotion. Therefore, ALYREF promotes tumor growth by binding to the m5C site of MAZ mRNA, increasing its stability, and suppressing p53 via MAZ to regulate the cycle, which facilitates the proliferation of HCC. Overall, our study revealed that ALYREF contributes to HCC proliferation through the MAZ-mediated p53-dependent cell cycle, and the co-expression of ALYREF and MAZ in clinical samples may serve as an effective prognostic indicator for HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ALYREF facilitates the proliferation of hepatocellular carcinoma via MAZ-mediated p53-dependent cell cycle promotion

Ma,

Liu,

Rong

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…In vitro and in vivo studies have identifiedthe RNA methyltransferase NSUN2 as primarily enzyme catalyzing m5C production in mRNAs, with m5C specifically recognized by the mRNA export adaptor ALYREF [ 46 ]. Recent research has linked ALYREF to the development of various tumors, including bladder cancer [ 47 , 48 ], breast cancer [ 49 ], neuroblastoma [ 50 ], hepatocellular carcinoma [ 51 , 52 ], glioblastoma [ 53 ], and non-small cell lung cancer [ 54 ]. These findings underscore the gene’s critical role in human cancer.…”

Section: Discussionmentioning

confidence: 99%

Pan-cancer analysis of RNA 5-methylcytosine reader (ALYREF)

YE,

TUO,

CHEN

et al. 2024

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The increasing interest in RNA modifications has significantly advanced epigenomic and epitranscriptomic technologies. This study focuses on the immuno-oncological impact of ALYREF in human cancer through a pancancer analysis, enhancing understanding of this gene's role in cancer. We observed differential ALYREF expression between tumor and normal samples, correlating strongly with prognosis in various cancers, particularly kidney renal papillary cell carcinoma (KIRP) and liver hepatocellular carcinoma (LIHC). ALYREF showed a negative correlation with most tumor-infiltrating cells in lung squamous cell carcinoma (LUSC) and lymphoid neoplasm diffuse large Bcell lymphoma (DLBC), while positive correlations were noted in LIHC, kidney chromophobe (KICH), mesothelioma (MESO), KIRP, pheochromocytoma and paraganglioma (PARD), and glioma (GBMLGG). Additionally, ALYREF expression was closely associated with tumor heterogeneity, stemness indices, and a high mutation rate in TP53 across these cancers. In conclusion, ALYREF may serve as an oncogenic biomarker in numerous cancers, meriting further research attention.

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“…The identified m5C methylation recognition proteins of eukaryotic mRNAs include Aly/REF export factor (ALYREF) ( 41 ), Fragile X mental retardation protein (FMRP) ( 42 ), Y-box binding protein (YBX)1, and YBX2 ( 43 ). ALYREF and FMRP are predominantly present in the nucleus, whereas YBX1 and YBX2 are in the cytoplasm ( 34 ).…”

Section: Biological Functions Of M5c Methylationmentioning

confidence: 99%

RNA m5C methylation modification: a potential therapeutic target for SARS-CoV-2-associated myocarditis

Xiong,

Li,

Qian

et al. 2024

Front. Immunol.

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The Corona Virus Disease (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has quickly spread worldwide and resulted in significant morbidity and mortality. Although most infections are mild, some patients can also develop severe and fatal myocarditis. In eukaryotic RNAs, 5-methylcytosine (m5C) is a common kind of post-transcriptional modification, which is involved in regulating various biological processes (such as RNA export, translation, and stability maintenance). With the rapid development of m5C modification detection technology, studies related to viral m5C modification are ever-increasing. These studies have revealed that m5C modification plays an important role in various stages of viral replication, including transcription and translation. According to recent studies, m5C methylation modification can regulate SARS-CoV-2 infection by modulating innate immune signaling pathways. However, the specific role of m5C modification in SARS-CoV-2-induced myocarditis remains unclear. Therefore, this review aims to provide insights into the molecular mechanisms of m5C methylation in SARS-CoV-2 infection. Moreover, the regulatory role of NSUN2 in viral infection and host innate immune response was also highlighted. This review may provide new directions for developing therapeutic strategies for SARS-CoV-2-associated myocarditis.

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ALYREF mediates RNA m5C modification to promote hepatocellular carcinoma progression

Cited by 24 publications

References 5 publications

ALYREF facilitates the proliferation of hepatocellular carcinoma via MAZ-mediated p53-dependent cell cycle promotion

ALYREF facilitates the proliferation of hepatocellular carcinoma via MAZ-mediated p53-dependent cell cycle promotion

Pan-cancer analysis of RNA 5-methylcytosine reader (ALYREF)

RNA m5C methylation modification: a potential therapeutic target for SARS-CoV-2-associated myocarditis

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