Novel miRNA genes deregulated by aberrant methylation in ovarian carcinoma are involved in metastasis

Логинов, В. И.; Пронина, И. В.; Burdennyy, A. M.; Филиппова, Е. А.; Kazubskaya, T. P.; Kushlinsky, D. N.; Уткин, Д. О.; Ходырев, Д. С.; Kushlinskii, N. E.; Dmitriev, Alexey A.; Брага, Э. А.

doi:10.1016/j.gene.2018.04.005

Cited by 58 publications

(38 citation statements)

References 52 publications

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“…DNA methylation is reported to lead to gene silencing via inhibiting gene transcription, which has become the most studied epigenetic mechanism [7]. Accumulated studies have showed that aberrant methylation of gene promoter regions is associated with occurrence, progression, and metastasis of several tumors, including ovarian carcinoma [8], gastric cancer [9] and so on. The profile of gene promoter methylation in TGCT was reported by several studies [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

A network-based approach to identify DNA methylation and its involved molecular pathways in testicular germ cell tumors

Cao

Tang

et al. 2019

J. Cancer

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Background : Testicular germ cell tumors (TGCT) is the most common testicular malignancy threaten young male reproductive health. This study aimed to identify aberrantly methylated-differentially expressed genes and pathways in TGCT by comprehensive bioinformatics analysis. Methods : Data of gene expression microarrays (GSE3218, GSE18155) and gene methylation microarrays (GSE72444) were collected from GEO database. Integrated analysis acquired aberrantly methylated-genes. Functional and pathway enrichment analysis were performed using DAVID database. Protein-protein interaction (PPI) network was constructed by STRING and App Mcode was used for module analysis. GEPIA platform and DiseaseMeth database were used for confirming the expression and methylation levels of hub genes. Finally, Human Protein Atlas database was performed to evaluate the prognostic significance. Results : Totally 604 hypomethylation-high expression and 147 hypermethylation-low genes were identified. The high expressed genes were enriched in biological processes of cell proliferation and migration. The top 8 hub genes of PPI network were GAPDH, VEGFA, PTPRC, RIPK4, MMP9, CSF1R, KRAS and FN1. After validation in GEPIA platform, all hub genes were elevated in TGCT tissues. Only MMP9, CSF1R and PTPRC showed hypomethylation-high expression status, which predicted the poor outcome of TGCT patients. Conclusion : Our study indicated possible aberrantly methylated-differentially expressed genes and pathways in TGCT by bioinformatics analysis, which may provide novel insights for unraveling pathogenesis of TGCT.

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Section: Introductionmentioning

confidence: 99%

A network-based approach to identify DNA methylation and its involved molecular pathways in testicular germ cell tumors

Cao

Tang

et al. 2019

J. Cancer

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“…However, inconsistent findings have also been reported. For example, miR-124-3p, miR-148a-3p, miR-203a, and miR-375 were detected exhibiting differential expression in EOC specimens with both downregulation and upregulation [ 114 , 116 , 117 , 118 , 119 ]. Several other miRNAs listed in Table 1 have also been shown to be either up- or down-regulated in different studies.…”

Section: Dysregulation Of Mirna Expression In Ovarian Cancermentioning

confidence: 99%

The Role of microRNAs in Epithelial Ovarian Cancer Metastasis

Nguyen

Yue

et al. 2020

IJMS

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Epithelial ovarian cancer (EOC) is the deadliest gynecological cancer, and the major cause of death is mainly attributed to metastasis. MicroRNAs (miRNAs) are a group of small non-coding RNAs that exert important regulatory functions in many biological processes through their effects on regulating gene expression. In most cases, miRNAs interact with the 3′ UTRs of target mRNAs to induce their degradation and suppress their translation. Aberrant expression of miRNAs has been detected in EOC tumors and/or the biological fluids of EOC patients. Such dysregulation occurs as the result of alterations in DNA copy numbers, epigenetic regulation, and miRNA biogenesis. Many studies have demonstrated that miRNAs can promote or suppress events related to EOC metastasis, such as cell migration, invasion, epithelial-to-mesenchymal transition, and interaction with the tumor microenvironment. In this review, we provide a brief overview of miRNA biogenesis and highlight some key events and regulations related to EOC metastasis. We summarize current knowledge on how miRNAs are dysregulated, focusing on those that have been reported to regulate metastasis. Furthermore, we discuss the role of miRNAs in promoting and inhibiting EOC metastasis. Finally, we point out some limitations of current findings and suggest future research directions in the field.

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“…Most deaths from ovarian cancer are attributed to distant metastasis. Metastasis, which is a multistep process, allows tumor cell diffuse from the primary sites to distant tissues [1,2]. Increasing investigations have demonstrated that the loss of cancer suppressors and the upregulation of oncogenes are associated with cancer cell metastasis [3,4].…”

Section: Introductionmentioning

confidence: 99%

Tumor-suppressor miRNA-27b-5p regulates the growth and metastatic behaviors of ovarian carcinoma cells by targeting CXCL1

Liu

Jing

Liu

et al. 2020

Preprint

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BackgroundMicroRNAs (miRNAs) play crucial functions in the progression of ovarian cancer. MicroRNA-27b-5p (miR-27b-5p) has been identified as a cancer-associated miRNA. Nevertheless, the expression profile of miR-27b-5p and its functions in ovarian cancer are unexplored.MethodsqRT-PCR and western blot analysis were used to detect the levels of miR-27b-5p and C-X-C motif chemokine ligand 1 (CXCL1). The impact of miR-27b-5p on ovarian cancer cells proliferation, migration and invasion in vitro were investigated using Cell Counting Kit-8 (CCK8), wound healing and Transwell, respectively. The expression of matrix metalloprotein-2/9 (MMP-2/9) were measured using immunofluorescence staining. Bioinformatics and luciferase reporter analysis were used to predict the target of miR-27b-5p. The growth of ovarian cancer cells in vivo was evaluated using transplanted tumor model.ResultsHere, we demonstrated that miR-27b-5p was downregulated in ovarian carcinoma cells and clinical specimens. Higher expression of miR-27b-5p was associated with an unfavorable overall survival in patients with ovarian cancer. Upregulation of miR-27b-5p decreased the viability, migration ability and invasion capacity of SKOV3 and OVCAR3 cell. MiR-27b-5p also inhibited the growth of SKOV3 cell in nude mice. Additionally, we verified that CXCL1 was a target of miR-27b-5p in ovarian carcinoma cells. Restoring the expression of CXCL1 abolished the inhibitory impacts of miR-27b-5p in ovarian cancer carcinoma cells.ConclusionThis research revealed that miR-27b-5p restrained the progression of ovarian carcinoma possibly via targeting CXCL1.

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Novel miRNA genes deregulated by aberrant methylation in ovarian carcinoma are involved in metastasis

Cited by 58 publications

References 52 publications

A network-based approach to identify DNA methylation and its involved molecular pathways in testicular germ cell tumors

A network-based approach to identify DNA methylation and its involved molecular pathways in testicular germ cell tumors

The Role of microRNAs in Epithelial Ovarian Cancer Metastasis

Tumor-suppressor miRNA-27b-5p regulates the growth and metastatic behaviors of ovarian carcinoma cells by targeting CXCL1

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