YTH domain family: potential prognostic targets and immune-associated biomarkers in hepatocellular carcinoma

Liu, Miaomiao; Zhao, Zijin; Cai, Yuan; Peng, Bi; Liang, Qiuju; Yan, Yuanliang; Xu, Zhijie

doi:10.18632/aging.203674

Cited by 16 publications

(11 citation statements)

References 41 publications

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“…Hepatocellular carcinoma is a fatal cancer featured with insidious onset, fast and invasive growth, high malignancy, high recurrence, and high mortality rate. 24 Globally, HCC is the sixth major cause of cancer-associated death. 2 Meanwhile, many HCC patients are of short survival time due to metastasis and early relapse after surgical resection.…”

Section: Discussionmentioning

confidence: 99%

Sortilin 1 regulates hepatocellular carcinoma progression by activating the PI3K/AKT signaling

Wang

Zhou

et al. 2022

Hum Exp Toxicol

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Background Sortilin 1 (SORT1) has been reported as an oncogene in several human tumors. Nonetheless, the biological functions of SORT1 in hepatocellular carcinoma (HCC) remain poorly understood. Methods Western blotting was employed for the determination of protein expression. Hepatocellular carcinoma cell viability, apoptosis, migration, and invasion were measured via CCK-8, flow cytometry, wound healing, and Transwell assays. Results Sortilin 1 was upregulated in HCC and closely associated with unsatisfactory outcomes of HCC patients. Furthermore, in vitro and in vivo assays revealed that SORT1 knockdown significantly diminished HCC cell proliferation and metastasis but accelerated HCC cell apoptosis; moreover, SORT1 depletion also restrained the growth of xenografted HCC tumors. Mechanistically, SORT1 activated PI3K/AKT signaling in HCC cells, thereby promoting the malignant behaviors of HCC cells. Conclusion This study demonstrated that SORT1 might promote HCC progression by activating PI3K/AKT signaling, indicating that SORT1 might be a promising target and biomarker for HCC treatment and prognosis.

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Section: Discussionmentioning

confidence: 99%

Sortilin 1 regulates hepatocellular carcinoma progression by activating the PI3K/AKT signaling

Wang

Zhou

et al. 2022

Hum Exp Toxicol

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“…The roles of m1A regulators in HCC also had been investigated in previous studies. The expression levels of readers, including YTHDF1, YTHDF2, and YTHDF3, are reported to upregulate in HCC tissues compared with adjacent tissues, and a positive correlation was detected between immune cell infiltration and the expression levels of YTHDF1, YTHDF2, and YTHDF3, revealing the functional roles of m1A regulators in modulating the infiltration of immune cells in HCC tissues [ 25 ]. As for erasers, consistent with our results, Wang et al reported an elevated ALKBH3 expression in HCC compared with adjuvant non-tumorous tissues, and found that patients with high ALKBH3 expression level displayed poor prognosis and the knockdown of ALKBH3 inhibits tumor cells proliferation, indicating the functional role of m1A modification in promoting cell cycle [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

m1A methylation modification patterns and metabolic characteristics in hepatocellular carcinoma

Tong

Wang

2022

BMC Gastroenterol

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Background The dysregulation of RNA methylation has been demonstrated to contribute to tumorigenicity and progression in recent years. However, the alteration of N1-methyladenosine (m1A) methylation and its role in hepatocellular carcinoma (HCC) remain unclear. Methods We systematically investigated the modification patterns of 10 m1A regulators in HCC samples and evaluated the metabolic characteristics of each pattern. A scoring system named the m1Ascore was developed using principal component analysis. The clinical value of the m1Ascore in risk stratification and drug screening was further explored. Results Three m1A modification patterns with distinct metabolic characteristics were identified, corresponding to the metabolism-high, metabolism-intermediate and metabolism-excluded phenotypes. Patients were divided into high- or low-m1Ascore groups, and a significant survival difference was observed. External validation confirmed the prognostic value of the m1Ascore. A nomogram incorporating the m1Ascore and other clinicopathological factors was constructed and had good performance for predicting survival. Two agents, mitoxantrone and doxorubicin, were determined to be potential therapeutic drugs for the high-risk group. Conclusion This study provided novel insights into m1A modification and metabolic heterogeneity in cancer, promoted risk stratification in the clinic from the perspective of m1A modification, and further guided individual treatment strategies.

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“…Although research on the mechanism of action of YTHDC2 in OA is limited, studies on the effect of m6a-related genes on immune cells in lung cancer showed that most of the YTH family members, especially YTHDC2, are signi cantly associated with in ltration of CD4 + T cells, CD8 + T cells, macrophages, and neutrophils. Furthermore, YTHDC2 is a promising biomarker and potential therapeutic target for lung cancer detection 36,37 . Based on our study results, YTHDC2 may affect cartilage tissues through lymphocyte stimulation-related pro-in ammatory factors.…”

Section: Discussionmentioning

confidence: 99%

Exploring the relationship between cartilage-associated m6a gene and osteoarthritis development based on bioinformatics and machine learning

Shi

Chen

2022

Preprint

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Purpose:This study aimed to analyze the expression of n6-methyladenosine (m6a)-related genes in osteoarthritis (OA), the relationship between m6a signature genes and clinical morbidity, and the correlation between m6a gene immune cells by using bioinformatics and random forest tree methods. Methods:OA-related microarrays were obtained from the GEO database. The m6a-related genes were extracted, and their differential gene expression was analyzed using R software. Appropriate gene screening methods were selected to obtain m6a disease signature genes; m6a clinical prediction models were established; decision curve analysis (DCA) was applied to verify the model’s accuracy. Typing was performed according to m6a expression, and genetic differences between typing and differences in immune infiltration were analyzed. The correlation between the differential genes and immune cells was also analyzed. Finally, the m6a differential genes were analyzed using Metascape. Results:Random forest tree screening was used to obtain the following m6a disease signature genes for cartilage in OA: METTL3, CBLL1, YTHDC1, YTHDC2, YTHDF1, and FMR1. A strong correlation was found between the expression of disease-characterizing genes and clinical disease incidence, which was higher when the total score was between 200 and 230. Based on the m6a gene expression in cartilage, the samples were divided into groups A and B, and METTL3, FMR1, and YTHDC2 had significant genetic differences in the two groups. Among the immune cells, activated CD4T, activated dendritic, natural killer T, and plasma cells were significantly different in the two groups. A significant correlation was found between the high expression of immune cells and the three m6a genes in group B. Metascape functional pathway analysis revealed that OA is mainly related to cell development, differentiation, morphological changes, chemotaxis, and inflammatory response, mainly involving the FRA pathway. Conclusion: The expression of m6a disease-characterizing genes is significantly correlated with the clinical incidence of OA, and the abnormal expression of m6a-related genes in OA cartilage is an important factor that may cause cartilage damage mainly by affecting immune cells, thus releasing relevant pro-inflammatory factors causing damage to chondrocytes.

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YTH domain family: potential prognostic targets and immune-associated biomarkers in hepatocellular carcinoma

Cited by 16 publications

References 41 publications

Sortilin 1 regulates hepatocellular carcinoma progression by activating the PI3K/AKT signaling

Sortilin 1 regulates hepatocellular carcinoma progression by activating the PI3K/AKT signaling

m1A methylation modification patterns and metabolic characteristics in hepatocellular carcinoma

Exploring the relationship between cartilage-associated m6a gene and osteoarthritis development based on bioinformatics and machine learning

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