Methylation of RILP in lung cancer promotes tumor cell proliferation and invasion

Lin, Jianbo; Zhuo, Yi; Yin, Yinhe; Qiu, Linbin; Li, Xu; Lai, Fan-Cai

doi:10.1007/s11010-020-03950-0

Cited by 13 publications

(9 citation statements)

References 30 publications

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“…Accumulating studies suggest that lysosomes are involved in tumorigenesis, drug resistance, and cancer therapy for various cancers, including prostate cancer [39], lung cancer [40], and BRCA [41]. Lysosomes manipulate growth factor signaling and provide nutrition in BRCA, therefore play a crucial role [42,43].…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Identification of Lysosome-related Biomarkers for Predicting Prognosis and Immunotherapeutic Response in Breast Cancer

Zhang

Wang

Duan

et al. 2023

Preprint

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Background Breast cancer (BRCA) is one of the most frequent malignant tumors in women worldwide. Lysosomes are known to regulate tumor cell proliferation by manipulating growth factor signaling and providing nutrition. However, the role of lysosomes and lysosome-related genes (LRGs) in BRCA is yet unclear. Therefore, this study aimed to identify the lysosomal-related biomarkers for predicting the prognosis and immunotherapeutic response of BRCA. Results Based on the expression of 15 prognostic LRGs, BRCA cases were divided into two subtypes with significantly different overall survival (OS). In all, 537 differentially expressed lysosome-related genes (DELRGs) were identified and they were significantly enriched in the PI3K-Akt signaling pathway, protein digestion and absorption, and regulation of actin cytoskeleton. Then, the risk model was constructed based on five biomarkers, namely, QPRT, EIF4EBP1, IGJ, UGDH, and IL1R1. The Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves revealed that the risk model could accurately predict the prognosis of BRCA cases, and age, stage, and risk score were regarded as independent prognostic indicators. According to Gene set enrichment analysis (GSEA), the risk model might be related to the cell cycle, cytokine receptor interaction, and ATP synthesis coupled electron transport pathways. Moreover, the risk score showed significant positive correlation with CTLA4, while negative correlation with PD1. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) indicated the expression levels of EIF4EBP1 and UGDH were significantly higher in BRCA tissue compared with normal samples. Conclusion We identified two BRCA subtypes based on LRGs and constructed a risk model using five biomarkers. These findings may provide a theoretical basis and reference value for research and treatment in the direction of lysosomes in BRCA.

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Identification of Lysosome-related Biomarkers for Predicting Prognosis and Immunotherapeutic Response in Breast Cancer

Zhang

Wang

Duan

et al. 2023

Preprint

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“…DNA methylation is the most common epigenetic modification mechanism and may contribute to a variety of tumors by inhibiting normal cell senescence and differentiation [41,42]. Many studies have shown that abnormal DNA methylation plays a crucial role in the malignant transformation and progression of LUAD [43][44][45]. To explore the mechanism of ANGPTL4 overexpression, we analyzed the relationship between the methylation and expression levels of ANGPTL4 in LUAD.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of ANGPTL4 in Lung Adenocarcinoma: A Meta-Analysis Based on Integrated TCGA and GEO Databases

Yang

Liu

Gao

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Lung adenocarcinoma (LUAD) is a common malignant tumor with a poor prognosis. Recent studies have found that angiopoietin-like 4 (ANGPTL4) is abnormally expressed in many tumors, so it can serve as a potential prognostic marker and therapeutic target. However, its prognostic value in LUAD remains unclear. We downloaded RNA sequence data for LUAD from The Cancer Genome Atlas (TCGA) database, methylation data from the University of California Santa Cruz genome database, and clinical information. R software (version 4.1.1) was applied to analyze the ANGPTL4 expression in LUAD and nontumor samples, and the correlation with clinical characteristics to assess its prognostic and diagnostic value. In addition, we analyzed the relationship between the ANGPTL4 expression and methylation levels. Tumor IMmune Estimation Resource (TIMER) tool was taken for immune infiltration analysis, and two Gene Expression Omnibus (GEO) datasets were combined for meta-analysis. Finally, differentially expressed genes (DEGs) related to ANGPTL4 were analyzed to clarify its function. As shown in our results, ANGPTL4 was upregulated in LUAD and was an independent risk factor for the diagnosis and prognosis of LUAD. The general methylation level and eight ANGPTL4 methylation sites were significantly negatively correlated with the ANGPTL4 expression. Furthermore, we found that B cell infiltration was negatively correlated with ANGPTL4 expression and was an independent risk factor. Meta-analysis showed that the high expression of ANGPTL4 was closely associated with a poor prognosis. 153 DEGs, including the matrix metalloproteinase family, the chemokines subfamily, and the collagen family, were correlated with ANGPTL4. In this study, we found that ANGPTL4 was significantly elevated in LUAD and was closely associated with the development and poor prognosis of LUAD, suggesting that ANGPTL4 may be a prognostic biomarker and a potential therapeutic target for LUAD.

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“…Moreover, it has been demonstrated that lysosome-related drugs may be linked to chemosensitizers and immunomodulators in cancer chemotherapy, and can enhance immune response by reversing the chelation of drugs in lysosome, thus playing a role in inhibiting lung cancer cells [26] . Notably, demethylation treatment can enhance the expression of lysosomes in lung cancer cells, possibly facilitating the development of lysosomal targeting or demethylation drugs for lung cancer treatment [14] . Besides, autophagy inhibitors can serve as potential antitumor drugs through inhibiting autophagy lysosome fusion [27] .…”

Section: Discussionmentioning

confidence: 99%

“…Jin et al [13] found that RNA methyltransferase METTL3 mediated m6A modification can promote mRNA translation to increase the resistance of lung cancer to tumor treatment and metastasis. Lung epichek, a 6-marker panel methylation-based plasma test, has shown strong performance in lung cancer prediction and detection of high proportions of early stage NSCLC and SCLC, while significantly improving predictive accuracy when combined with the established risk factors [14] .…”

Section: Introductionmentioning

confidence: 99%

Microarray analysis of genes with differential expression of m6A methylation in lung cancer

Zhang

et al. 2021

Bioscience Reports

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Purpose: N6-methyladenosine (m6A) is among the most abundant mRNA modifications in eukaryote. The aim of this study was to investigate function of m6A mRNA methylation in lung cancer and the underlying mechanism. Methods: Microarray analysis was performed to detect the differences in RNA expression between cancerous and adjacent non-cancerous tissue samples. The target mRNAs were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Hierarchical clustering of RNAs was conducted to identify distinct m6A methylation or expression patterns between the samples. Results: In this study, some differentially expressed genes (DEGs) of mRNAs were identified, including up-regulated SPP1 and down-regulated pRB. Functional enrichment analysis revealed that while differential hypermethylation was related to cell cycle, intracellular part and protein binding, the main pathway involved herpes simplex virus 1 infection related to down-regulated AKT, Araf1 and BCL2A1. In the meantime, sexual reproduction, cohesin complex and portein C-terminus binding was functionally linked to differential hypomethylation, while fluid shear stress and atherosclerosis were identified as the main pathways related to up-regulated GST and CNP. Conclusions: We showed that lung cancer development involved differential expression of SPP1 and pRB mRNA, as well as m6A mRNA methylation in AKT, APAF1, BCL2A1, GST and CNP genes.

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Methylation of RILP in lung cancer promotes tumor cell proliferation and invasion

Cited by 13 publications

References 30 publications

WITHDRAWN: Identification of Lysosome-related Biomarkers for Predicting Prognosis and Immunotherapeutic Response in Breast Cancer

WITHDRAWN: Identification of Lysosome-related Biomarkers for Predicting Prognosis and Immunotherapeutic Response in Breast Cancer

Prognostic Significance of ANGPTL4 in Lung Adenocarcinoma: A Meta-Analysis Based on Integrated TCGA and GEO Databases

Microarray analysis of genes with differential expression of m6A methylation in lung cancer

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