ALYREF associated with immune infiltration is a prognostic biomarker in hepatocellular carcinoma

Wang, Zhenzhen; Tao, Meng; Yang, Mingya; Wang, Wei; Zhang, Yan; Liu, Yu; Han, An-Qi; Wu, Jin; Wang, Huixiao; Qian, Bo; Zhu, Lingjun

doi:10.1016/j.tranon.2022.101441

Cited by 10 publications

(9 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

YE,

TUO,

CHEN

et al. 2024

View full text Add to dashboard Cite

show abstract

“…Dysregulation of ALYREF can mediate alterations in the biological function of a variety of tumors. A recent study has found that expression of ALYREF is related to the prognosis of LIHC patients and participated in the immune regulation of LIHC 16 , 17 , suggesting an important role for LIHC microenvironment. In addition, ALYREF promotes regional lymph node metastasis in oral squamous cell carcinoma and enhances cell proliferation in bladder cancer 15 , 40 .…”

Section: Discussionmentioning

confidence: 99%

ALYREF-mediated RNA 5-Methylcytosine modification Promotes Hepatocellular Carcinoma Progression Via Stabilizing EGFR mRNA and pSTAT3 activation

Nulali,

Zhang,

Long

et al. 2024

Int. J. Biol. Sci.

View full text Add to dashboard Cite

5-Methylcytosine (m5C) is one of the most ubiquitous modifications of mRNA and contributes to cancer pathogenesis. Aly/REF export factor (ALYREF), an m5C reader, is associated with the prognosis of liver hepatocellular carcinoma (LIHC). However, the effects of ALYREF on the progression of LIHC and the underlying molecular mechanisms remains elusive. Through an analysis of an online database and 3 independent LIHC cohorts, we found that ALYREF was markedly elevated in human liver cancer tissues and was significantly correlated with LIHC clinicopathological parameters, including Ki67 + cell rate, high-grade TNM stage, and poor prognosis. Several experiments were conducted to investigate the molecular basis and functional role of ALYREF-related progression in this study. ALYREF could enhance LIHC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro and tumor formation in vivo . Mechanistically, ALYREF promoted the progression of human LIHC through EGFR pathways. Furthermore, ALYREF could directly bind to the m5C modification site of EGFR 3' untranslated region (3' UTR) to stabilize EGFR mRNA. Collectively, ALYREF played a crucial oncogenic role in LIHC via the stabilization of EGFR mRNA and subsequent activation of the STAT3 signaling pathway. Our results may help to elucidate the potential mechanisms of ALYREF-induced m5C modification in the progression of human LIHC.

show abstract

“…The disorder of 5-methylcytidine (m 5 C) modi cation on RNA is closely related to the occurrence and development of various cancers [17][18][19]. Studies have detected the expression levels of thirteen m 5 C regulators and found that ALYREF expression is signi cantly higher in HCC tumors [20,21]. ALYREF is an m 5 C-binding protein that recognizes m 5 C-modi ed mRNAs and in uences their stability [22].…”

Section: Discussionmentioning

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

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.

show abstract

ALYREF associated with immune infiltration is a prognostic biomarker in hepatocellular carcinoma

Cited by 10 publications

References 37 publications

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

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

ALYREF-mediated RNA 5-Methylcytosine modification Promotes Hepatocellular Carcinoma Progression Via Stabilizing EGFR mRNA and pSTAT3 activation

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

Contact Info

Product

Resources

About