DNA methyltransferase3a expression is an independent poor prognostic indicator in gastric cancer

Cao, Xueyuan; Ma, Haiying; Shang, Yue; Jin, Meishan; Kong, Fei; Jia, Zhifang; Cao, Donghui; Wang, Yinping; Suo, Jian; Jiang, Jing

doi:10.3748/wjg.v20.i25.8201

Cited by 40 publications

(31 citation statements)

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“…3C and D revealed the expression profile of the DNMTs similar to IHC results. Substantial research has shown that DNA methylation appears in the cancerous and para-cancerous tissues (30), these data are in agreement with our present study.…”

Section: Expression Of Dnmts Is Significantly Upregulated In Para-carsupporting

confidence: 94%

Expression of DNA methyltransferases and target microRNAs in human tissue samples related to sporadic colorectal cancer

et al. 2016

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Abstract. Tissue microenvironment functions as a pivotal mediator in colorectal carcinogenesis, and its alteration can cause some important cellular responses including epigenetic events. The present study examined histologically altered tissue structure, DNA methyltransferases (DNMTs) and their corresponding expression of target microRNAs (miRNA). Tissues resected by surgery were from primary colorectal carcinoma. These samples were from three locations: and were ≥10, 5 and ≤2 cm away from the proximal lesion of colon cancer, and marked as no. 1, no. 2 and no. 3, respectively. Histological alteration was assessed by H&E staining, expression of DNMT1, DNMT3A, and DNMT3B was detected by immunohistochemistry and western blotting, microarray chip was used to screen distinguishable miRNAs and miRNAs targeting DNMTs whose validation assay was performed by quantitative real-time polymerase chain reaction (qRT-PCR). Our results revealed that normal crypt structure was shown in no. 1, while many aberrant crypt foci appeared in no. 3. Significant upregulation of DNMT1, DNMT3A, and DNMT3B expression was found in para-carcinoma tissues, compared with the histopathologically unchanged tissues (P<0.05), furthermore, distinguishable expression profiling was observed of target miRNAs in tissues with different distance. Our results provide additional insights for future research of colorectal carcinogenesis by introducing the tissue microenvironment.

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Section: Expression Of Dnmts Is Significantly Upregulated In Para-carsupporting

confidence: 94%

Expression of DNA methyltransferases and target microRNAs in human tissue samples related to sporadic colorectal cancer

et al. 2016

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“…As important DNMTs for de novo methylation [16,17], DNMT3A and 3B have been found to be overexpressed in various tumors including GBM [18][19][20][21], and responsible for the epigenetic silencing of multiple tumor suppressor genes [22]. Although it has been accepted that miR-29s could restore the expression of tumor suppressors by silencing DNMT3A/3B [4,18,[23][24][25][26], the real mechanisms are still controversial.…”

Section: Discussionmentioning

confidence: 97%

miR-29s inhibit the malignant behavior of U87MG glioblastoma cell line by targeting DNMT3A and 3B

Sun

Shi

et al. 2015

Neuroscience Letters

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“…Hypermethylation is responsible for the silencing of TSGs involved in tumorigenesis (19,20). DNMT3A, like other DNMT family members, is involved in tumorigenesis, differentiation and metastasis (21,22), but the correlation between DNMT3A and NSCLCs remains largely unknown. In the last ten years, miRNAs have been noted to play a significant role in the initiation and progression of NSCLCs (23,24).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-101 suppresses progression of lung cancer through the PTEN/AKT signaling pathway by targeting DNA methyltransferase 3A

et al. 2016

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It is well established that transcriptional silencing of critical tumor suppressor genes by DNA methylation is a fundamental process in the initiation of lung cancer. However, the involvement of microRNAs (miRNAs) in restoring abnormal DNA methylation patterns in lung cancer is not well understood. Therefore, and since miRNA-101 is complementary to the 3′-untranslated region of DNA methyltransferase 3A (DNMT3A), we investigated whether miRNA-101 could restore normal DNA methylation patterns in lung cancer cell lines. Bioinformatics has indicated that DNMT3A is a major target of miR-101. In addition, the overexpression of miR-101 downregulates DNMT3A. Using a methylation-specific polymerase chain reaction assay, we demonstrated that methylation of the phosphatase and tensin homolog (PTEN) promoter was reduced in A549 cells transfected with miR-101, but not in the transfected control. Furthermore, overexpression of miR-101 and silencing of DNMT3A suppressed lung cell proliferation and S/G2 transition, and increased apoptosis through the PTEN/AKT pathway in vitro. Furthermore, we observed the opposite phenomenon in A549 cells transfected with a miR-101 inhibitor. Subsequent investigation revealed that overexpression of miR-101 significantly inhibited the tumorigenicity of A549 cells in a nude mouse xenograft model. These results demonstrate that miR-101 affects lung cancer progression through the PTEN/AKT signaling pathway by targeting DNMT3A in lung cells, suggesting that miR-101 may be a novel potential therapeutic strategy in lung cancer treatment.

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DNA methyltransferase3a expression is an independent poor prognostic indicator in gastric cancer

Abstract: The results suggest that expression of DNMT3a is an independent poor prognostic indicator in gastric cancer. DNMT3a might play an important role in gastric carcinogenesis.

Cited by 40 publications

References 0 publications

Expression of DNA methyltransferases and target microRNAs in human tissue samples related to sporadic colorectal cancer

Expression of DNA methyltransferases and target microRNAs in human tissue samples related to sporadic colorectal cancer

miR-29s inhibit the malignant behavior of U87MG glioblastoma cell line by targeting DNMT3A and 3B

MicroRNA-101 suppresses progression of lung cancer through the PTEN/AKT signaling pathway by targeting DNA methyltransferase 3A

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