Deregulation of DNMT1, DNMT3B and miR-29s in Burkitt lymphoma suggests novel contribution for disease pathogenesis

Robaina, Marcela Cristina; Mazzoccoli, Luciano; Arruda, Viviane Oliveira; Reis, Flaviana Ruade de Souza; Apa, Alexandre Gustavo; Rezende, Lídia Maria Magalhães de; Klumb, Claudete Esteves

doi:10.1016/j.yexmp.2015.03.006

Cited by 63 publications

(45 citation statements)

References 67 publications

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“…Dysregulation of the miR-200 family has increasingly been noted in various types of cancer, including breast cancer. Accumulating data show that promoter hypermethylation mediated by DNMT OE is an important epigenetic regulatory mechanism of abnormal miR expression (44,45). In melanoma, a significant decrease in miR-200a expression modulated by DNA hypermethylation was observed at CpG promoter sites (46).…”

Section: Discussionmentioning

confidence: 99%

FEN1 mediates miR‐200a methylation and promotes breast cancer cell growthviaMET and EGFR signaling

Zeng

Zhao

et al. 2019

FASEB j.

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Flap endonuclease 1 (FEN1) is recognized as a pivotal factor in DNA replication, long‐patch excision repair, and telomere maintenance. Excessive FEN1 expression has been reported to be closely associated with cancer progression, but the specific mechanism has not yet been explored. In the present study, we demonstrated that FEN1 promoted breast cancer cell proliferation via an epigenetic mechanism of FEN1‐mediated up‐regulation of DNA methyltransferase (DNMT)1 and DNMT3a. FEN1 was proved to interact with DNMT3a through proliferating cell nuclear antigen (PCNA) to suppress microRNA (miR)‐200a‐5p expression mediated by methylation. Furthermore, miR‐200a‐5p was identified to repress breast cancer cell proliferation by inhibiting the expression of its target genes, hepatocyte growth factor (MET), and epidermal growth factor receptor (EGFR). Overall, our data surprisingly demonstrate that FEN1 promotes breast cancer cell growth via the formation of FENl/PCNA/DNMT3a complex to inhibit miR‐200a expression by DNMT‐mediated methylation and to recover the target genes expression of miR‐200a, MET, and EGFR. The novel epigenetic mechanism of FEN1 on proliferation promotion provides a significant clue that FEN1 might serve as a predictive biomarker and therapeutic target for breast cancer.—Zeng, X., Qu, X., Zhao, C., Xu, L., Hou, K., Liu, Y., Zhang, N., Feng, J., Shi, S., Zhang, L., Xiao, J., Guo, Z., Teng, Y., Che, X. FEN1 mediates miR‐200a methylation and promotes breast cancer cell growth via MET and EGFR signaling. FASEB J. 33, 10717–10730 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

FEN1 mediates miR‐200a methylation and promotes breast cancer cell growthviaMET and EGFR signaling

Zeng

Zhao

et al. 2019

FASEB j.

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“…DNMT1 maintains methylation during DNA replication and repair, while the function of DNMT2 is not yet clear (47). Several studies have shown that abnormal DNA methylation is closely related to tumorigenesis and that the expression of DNMTs in cancerous tissues is increased (48,49). However, histone methylation and DNA methylation were initially thought to be two separate gene silencing systems.…”

Section: Discussionmentioning

confidence: 99%

Role of HOTAIR in the diagnosis and prognosis of acute leukemia

et al. 2016

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HOX antisense intergenic RNA (HOTAIR), a long non-coding RNA, plays an important role in the development of many types of cancers. Its function in acute leukemia (AL), however, has not been examined. The present study investigated the role of HOTAIR and its downstream genes in AL, and determined whether it could act as a molecular marker for prediction of leukemia development and prognosis. Real-time quantitative PCR was used to examine the expression of each gene in the HOTAIR signaling pathway in AL patients. The relationship between expression of HOTAIR and downstream genes and AL prognosis was analyzed. Expression of HOTAIR in patients with acute monocytic leukemia (M5) was increased as compared to controls (P<0.05). Compared to patients with low HOTAIR expression, overall survival and event-free survival of patients with high HOTAIR expression was significantly reduced. In addition, the expression of downstream genes in the HOTAIR signaling pathway including EZH2, LSD1, DNMT3A and DNMT3B was significantly increased in AL patients, and showed a significant positive correlation with high expression of HOTAIR (P<0.05). In conclusion, HOTAIR was closely related with a poor prognosis in AL patients. It may be involved in the development of leukemia by mediating methylation of DNA and histones.

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“…studies have shown that some of microRNAs, including miR29b, are able to directly target DNMT3B and induce hypomethylation and retrieve the initial state of tumor suppressor genes in acute myeloid leukemia and Burkitt's lymphoma. 32,33 In the present study, we examined the effects of miR-339 and miR-766 expressing lentiviruses on HCT116 and SW480 colon cancer cell lines, along with HUVEC as a representative of a normal cell. Selection of these microRNAs was based on the prediction of intriguing complementarity to 3 0 UTR region of DNMT3B gene.…”

Section: Discussionmentioning

confidence: 99%

MiR-339 and especially miR-766 reactivate the expression of tumor suppressor genes in colorectal cancer cell lines through DNA methyltransferase 3B gene inhibition

Afgar

Fard-Esfahani

Mehrtash

et al. 2016

Cancer Biology & Therapy

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It is observed that upregulation of DNMT3B enzyme in some cancers, including colon cancer, could lead to silencing of tumor suppressor genes. MiR-339 and miR-766 have been predicted to target 3 0 UTR of DNMT3B gene. Luciferase reporter assay validated that individual and co-transfection of miR-766 and miR-339 into the HEK293T cell reduced luciferase activity to 26% § 0.41%, 43% § 0.42 and 64% § 0.52%, respectively, compared to the control (P < 0.05). Furthermore, transduction of miR-339 and miR-766 expressing viruses into colon cancer cell lines (SW480 and HCT116) decreased DNMT3B expression (1.5, 3-fold) and (3, 4-fold), respectively. In addition, DNA methylation of some tumor suppressor genes decreased. Expression of these genes such as SFRP1 (2 and 1.6-fold), SFRP2 (0.07 and 4-fold), WIF1 (0.05 and 4-fold), and DKK2 (2 and 4-fold) increased in SW-339 and SW-766 cell lines; besides, expression increments for these genes in HCT-339 and HCT-766 cell lines were (2.8, 4-fold), (0.005, 1.5-fold), (1.7 and 3-fold) and (0.04, 1.7-fold), respectively. Also, while in SW-766, cell proliferation reduced to 2.8% and 21.7% after 24 and 48 hours, respectively, SW-339 showed no reduced proliferation. Meanwhile, HCT-766 and HCT-339 showed (3.5%, 12.8%) and (18.8%, 33.9%) reduced proliferation after 24 and 48 hours, respectively. Finally, targeting DNMT3B by these miRs, decreased methylation of tumor suppressor genes such as SFRP1, SFRP2, WIF1 and DKK2 in the mentioned cell lines, and returned the expression of these tumor suppressor genes which can contribute to lethal effect on colon cancer cells and reducing tumorigenicity of these cells.

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Deregulation of DNMT1, DNMT3B and miR-29s in Burkitt lymphoma suggests novel contribution for disease pathogenesis

Cited by 63 publications

References 67 publications

FEN1 mediates miR‐200a methylation and promotes breast cancer cell growthviaMET and EGFR signaling

FEN1 mediates miR‐200a methylation and promotes breast cancer cell growthviaMET and EGFR signaling

Role of HOTAIR in the diagnosis and prognosis of acute leukemia

MiR-339 and especially miR-766 reactivate the expression of tumor suppressor genes in colorectal cancer cell lines through DNA methyltransferase 3B gene inhibition

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