The impact of the RASSF1C and PIWIL1 on DNA methylation: the identification of GMIP as a tumor suppressor

Amaar, Yousef G.; Reeves, Mark E.

doi:10.18632/oncotarget.27795

Cited by 10 publications

(6 citation statements)

References 40 publications

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“…Lin – CD24 –/low CD44 + or ALDH + cell subpopulations have been well-validated as CSCs in human breast cancer tumors ( Al-Hajj et al, 2003 ; Ginestier et al, 2007 ), which are characterized by self-renewal, differentiation, and have the strong capability to regenerate tumors after transplantation in vivo . The aberrant expression of PIWI proteins and piRNAs in breast CSCs have been recently reported ( Amaar and Reeves, 2020 ; Lü et al, 2020 ). The regulation of CSC expansion by piR-016658 and piR-016975 was demonstrated in our previous study ( Lü et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

piRNA-823 Is Involved in Cancer Stem Cell Regulation Through Altering DNA Methylation in Association With Luminal Breast Cancer

Ding

Wang

et al. 2021

Front. Cell Dev. Biol.

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Cancer stem cells (CSCs) are believed to be the main source of cancer relapse and metastasis. PIWI-interacting small non-coding RNAs (piRNAs) have been recently recognized to be relevant to cancer biology. Whether and how piRNAs regulate human CSCs remain unknown. Herein, upregulation of piR-823 was identified in tested luminal breast cancer cells, especially in the luminal subtype of breast CSCs. Enforced expression or targeted knockdown of piR-823 demonstrated its oncogenic function in regulating cell proliferation and colony formation in MCF-7 and T-47D breast cancer cells. In addition, piR-823 induced ALDH (+) breast CSC subpopulation promoted the expression of stem cell markers including OCT4, SOX2, KLF4, NANOG, and hTERT, and increased mammosphere formation. Tail vein injection of magnetic nanoparticles carrying anti-piR-823 into the mammary gland of tumor-burdened mice significantly inhibited tumor growth in vivo. DNA methyltransferases (DNMTs) including DNMT1, DNMT3A, and DNMT3B were demonstrated to be the downstream genes of piR-823, which regulate gene expression by maintaining DNA methylation. piR-823 increased the expression of DNMTs, promoted DNA methylation of gene adenomatous polyposis coli (APC), thereby activating Wnt signaling and inducing cancer cell stemness in the luminal subtype of breast cancer cells. The current study not only revealed a novel mechanism through which piRNAs contribute to tumorigenesis in breast cancer by regulating CSCs, but also provided a therapeutic strategy using non-coding genomes in the suppression of human breast cancer.

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Section: Introductionmentioning

confidence: 99%

piRNA-823 Is Involved in Cancer Stem Cell Regulation Through Altering DNA Methylation in Association With Luminal Breast Cancer

Ding

Wang

et al. 2021

Front. Cell Dev. Biol.

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“…GMIP is a protein coding gene that encodes ARHGAP family of Rho/Rac/Cdc42-like GTPase activating proteins. In lung cancer, overexpression of GMIP was associated with longer survival; in the null mice model with a xenografted tumor of A549 cells, GMIP treatment has once been proved to induce autophagy and reduce tumor growth ( Hsin et al, 2011 ; Amaar and Reeves, 2020 ). IFI16 modulates p53 function and inhibits cell growth in the Ras/Raf signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

A New Prognostic Risk Score: Based on the Analysis of Autophagy-Related Genes and Renal Cell Carcinoma

Guan

et al. 2022

Front. Genet.

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Introduction: Clear cell renal cell carcinoma (ccRCC) patients suffer from its high recurrence and metastasis rate, and a new prognostic risk score to predict individuals with high possibility of recurrence or metastasis is in urgent need. Autophagy has been found to have a dual influence on tumorigenesis. In this study we aim to analyze autophagy related genes (ATGs) and ccRCC patients and find a new prognostic risk score. Method: Analyzing differential expression genes (DEGs) in TCGA-KIRC dataset, and took intersection with ATGs. Through lasso, univariate, and multivariate cox regression, DEGs were chosen, and the coefficients and expression levels of them were components constructing the formula of risk score. We analyzed mRNA expression of DEGs in tumor and normal tissue in ONCOMINE database and TCGA-KIRC dataset. The Human Protein Atlas (HPA) was used to analyze protein levels of DEGs. The protein-protein interaction (PPI) network was examined in STRING and visualized in cytoscape. Functional enrichment analysis was performed in RStudio. To prove the ability and practicibility of risk score, we analyzed univariate and multivariate cox regression, Kaplan-Meier curve (K-M curve), risk factor association diagram, receiver operating characteristic curve (ROC curve) of survival and nomogram, and the performance of nomogram was evaluated by calibration curve. Then we further explored functional enrichment related to risk groups through Gene Set Enrichment Analysis (GSEA), weighted gene co-expression network analysis (WGCNA), and Metascape database. At last, we investigated immune cell infiltration of DEGs and two risk groups through TIMER database and “Cibersort” algorithm.Result: We identified 7 DEGs (BIRC5, CAPS, CLDN7, CLVS1, GMIP, IFI16, and TCIRG1) as components of construction of risk score. All 7 DEGs were differently expressed in ccRCC and normal tissue according to ONCOMINE database and TCGA-KIRC dataset. Functional enrichment analysis indicated DEGs, and their most associated genes were shown to be abundant in autophagy-related pathways and played roles in tumorigenesis and progression processes. A serious analysis proved that this risk score is independent from the risk signature of ccRCC patients.Conclusion: The risk score constructed by 7 DEGs had the ability of predicting prognosis of ccRCC patients and was conducive to the identification of novel prognostic molecular markers. However, further experiment is still needed to verify its ability and practicability.

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“…Wu’s study indicates that the overexpression of LV-has-piR-011186 binding with a particular sequence recruits DNA and histone-methylating proteins to the CDKN2 promoter gene, leading to the result of the promotion of cell proliferation, as well as the inhibition of cell apoptosis in U937 leukemia cells [ 93 ]. In lung cancer, RASSF1C, a major member of the RASSF1 gene family [ 115 , 116 ], can encourage the expression of PIWIL1, as well as the modulation of piRNA’s expression [ 117 ]. This research presents us the RASSF1C/PIWIL1/piRNA axis, modulating the Gem Interacting Protein (GMIP) mRNA expression by DNA methylation in lung cancer, and thus affecting the migration of cancer cells.…”

Section: Epigenetic Regulatory Mechanism Of Piwi/pirnas In Human Cancersmentioning

confidence: 99%

The epigenetic regulatory mechanism of PIWI/piRNAs in human cancers

et al. 2023

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PIWI proteins have a strong correlation with PIWI-interacting RNAs (piRNAs), which are significant in development and reproduction of organisms. Recently, emerging evidences have indicated that apart from the reproductive function, PIWI/piRNAs with abnormal expression, also involve greatly in varieties of human cancers. Moreover, human PIWI proteins are usually expressed only in germ cells and hardly in somatic cells, so the abnormal expression of PIWI proteins in different types of cancer offer a promising opportunity for precision medicine. In this review, we discussed current researches about the biogenesis of piRNA, its epigenetic regulatory mechanisms in human cancers, such as N6-methyladenosine (m6A) methylation, histone modifications, DNA methylation and RNA interference, providing novel insights into the markers for clinical diagnosis, treatment and prognosis in human cancers.

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The impact of the RASSF1C and PIWIL1 on DNA methylation: the identification of GMIP as a tumor suppressor

Cited by 10 publications

References 40 publications

piRNA-823 Is Involved in Cancer Stem Cell Regulation Through Altering DNA Methylation in Association With Luminal Breast Cancer

piRNA-823 Is Involved in Cancer Stem Cell Regulation Through Altering DNA Methylation in Association With Luminal Breast Cancer

A New Prognostic Risk Score: Based on the Analysis of Autophagy-Related Genes and Renal Cell Carcinoma

The epigenetic regulatory mechanism of PIWI/piRNAs in human cancers

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