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MiR-137 is a tumor suppressor in endometrial cancer and is repressed by DNA hypermethylation.

ABSTRACT: Endometrial cancer is the most common gynecological cancer in the United States. We wanted to identify epigenetic aberrations involving microRNAs (miRNAs), whose genes become hypermethylated in endometrial primary tumors. By integrating known miRNA sequences from the miRNA database (miRBase) with DNA methylation data from methyl-CpG-capture sequencing, we identified 111 differentially methylated regions (DMRs) associated with CpG islands (CGIs) and miRNAs. Among them, 22 DMRs related to 29 miRNAs and within 8?kb of CGIs were hypermethylated in endometrial tumors but not in normal endometrium. miR-137 was further validated in additional endometrial primary tumors. Hypermethylation of miR-137 was found in both endometrioid and serous endometrial cancer (P?

SUBMITTER: Zhang W

PROVIDER: S-EPMC6214735 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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miR-137 is a tumor suppressor in endometrial cancer and is repressed by DNA hypermethylation.

Zhang Wei W Chen Jo-Hsin JH Shan Tianjiao T Aguilera-Barrantes Irene I Wang Li-Shu LS Huang Tim Hui-Ming TH Rader Janet S JS Sheng Xiugui X Huang Yi-Wen YW

Laboratory investigation; a journal of technical methods and pathology 20180628 11

Endometrial cancer is the most common gynecological cancer in the United States. We wanted to identify epigenetic aberrations involving microRNAs (miRNAs), whose genes become hypermethylated in endometrial primary tumors. By integrating known miRNA sequences from the miRNA database (miRBase) with DNA methylation data from methyl-CpG-capture sequencing, we identified 111 differentially methylated regions (DMRs) associated with CpG islands (CGIs) and miRNAs. Among them, 22 DMRs related to 29 miRNA ...[more]

PMID: 29955087

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Tumor-suppressor role of miR-139-5p in endometrial cancer.

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Project description:Epigenetic changes play significant roles in cancer development. UHRF1, an epigenetic regulator, has been shown to be overexpressed and to coordinate tumor suppressor gene (TSG) silencing in several cancers. In a previous study, we found that UHRF1 promoted gastric cancer (GC) invasion and metastasis. However, the role and underlying mechanism of UHRF1 in GC carcinogenesis remain largely unknown. In the present study, we investigated UHRF1 expression and function in GC proliferation and explored its downstream regulatory mechanism. The results demonstrated that UHRF1 overexpression was an independent and significant predictor of GC prognosis. Downregulation of UHRF1 suppressed GC proliferation and growth in vitro and in vivo, and UHRF1 upregulation showed opposite effects. Furthermore, downregulation of UHRF1 reactivated 7 TSGs, including CDX2, CDKN2A, RUNX3, FOXO4, PPARG, BRCA1 and PML, via promoter demethylation. These results provide insight into the GC proliferation process, and suggest that targeting UHRF1 represents a new therapeutic approach to block GC development.

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Hepatitis B virus X protein inhibits tumor suppressor miR-205 through inducing hypermethylation of miR-205 promoter to enhance carcinogenesis.

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