microRNA-7 Suppresses the Invasive Potential of Breast Cancer Cells and Sensitizes Cells to DNA Damages by Targeting Histone Methyltransferase SET8

Yu, Na; Huangyang, Peiwei; Yang, Xiaohan; Han, Xiao; Yan, Ruorong; Jia, Hong-Ti; Shang, Yongfeng; Sun, Luyang

doi:10.1074/jbc.m113.475657

Cited by 46 publications

(38 citation statements)

References 51 publications

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“…SET8 also called PR-Set7/9, KMT5A or SETD8, is one of the SET domain-containing methyltransferases that specifically targets histone H4 lysine 20 (H4K20) for monomethylation, and which exerts diverse biological processes, including activation or silencing of gene transcription (35,36), maintaining chromosome structure and stability (37,38), regulating the cell cycle and preventing premature chromatin compaction in the S phase (39,40), and rescuing and degrading DNA damage (41,42). Yu et al found that miR-7 suppressed the invasive potential of breast cancer cells by targeting SET8 (43). However, the role of SET8 in cervical cancer metastasis and how the expression of SET8 is regulated are poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA XLOC_006390 promotes cervical cancer proliferation and metastasis through the regulation of SET domain containing 8

Luan

Wang

2017

Oncology Reports

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The long non-coding RNA (lncRNA) XLOC_006390 is increased in various human cancer tissues and it plays important roles in cell growth and migration. However, the role of lncRNA XLOC_006390 in the progression and metastasis of cervical cancer has not been evaluated and remains unclear. In the present study, we hypothesized that lncRNA XLOC_006390 is also increased in cervical cancer, and upregulation of lncRNA XLOC_006390 contributes to cervical cancer metastasis. The expression of lncRNA XLOC_006390 in cervical cancer tissues and cell lines was analyzed using quantitative reverse-transcription-polymerase chain reaction (qRT-PCR). RNA interference approach and an overexpression system were used to investigate the cellular functions of XLOC_006390 and SET domain containing 8 (SET8). Cell Counting Kit-8 (CCK-8) assay was performed to detect cell proliferation. Cell migration and invasion abilities were evaluated by Transwell assays. Western blotting and immunofluorescence were performed to detect SET8 protein expression. The results revealed that XLOC_006390 was increased in cervical cancer tissues. Patients with high XLOC_006390 expression were associated with FIGO stages III and IV (P=0.0170), lymphatic metastasis (P=0.0078) and distant metastasis (P=0.0025). Furthermore, SET8 was also increased in cervical cancer tissues and its expression was positively associated with XLOC_006390, and XLOC_006390 regulated SET8 expression. In addition, knockdown or overexpression of XLOC_006390 and SET8 expression suppressed or promoted cervical cancer cell proliferation, migration and invasion in vitro, respectively. In conclusion, our data suggest that lncRNA XLOC_006390 promotes cervical cancer cell growth and metastasis through the regulation of SET8, at least partly, which indicate the critical roles of XLOC_006390 and SET8 in cervical cancer progression and metastasis.

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Section: Discussionmentioning

confidence: 99%

Long non-coding RNA XLOC_006390 promotes cervical cancer proliferation and metastasis through the regulation of SET domain containing 8

Luan

Wang

2017

Oncology Reports

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“…Setd8 and H4K20me1 are also thought to be transcriptional regulators (7,15,(17)(18)(19)(20)(21)(22)(23)(24)(25); however, in contrast to some of the better-characterized histone modifications (e.g., histone H3 lysine 4 methylation), the influence of this epigenetic pathway on gene expression has not been clearly defined. Disruption of the Setd8/H4K20me1 pathway has been associated with a number of human cancers, including leukemia (26)(27)(28)(29)(30), highlighting the relevance of this pathway to human health and disease.…”

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confidence: 99%

Histone Methyltransferase Setd8 Represses Gata2 Expression and Regulates Erythroid Maturation

Malik

Getman

Steiner

2015

Molecular and Cellular Biology

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Setd8 is the sole histone methyltransferase in mammals capable of monomethylating histone H4 lysine 20 (H4K20me1). Setd8 is expressed at significantly higher levels in erythroid cells than any other cell or tissue type, suggesting that Setd8 has an erythroidcell-specific function. To test this hypothesis, stable Setd8 knockdown was established in extensively self-renewing erythroblasts (ESREs), a well-characterized, nontransformed model of erythroid maturation. Knockdown of Setd8 resulted in impaired erythroid maturation characterized by a delay in hemoglobin accumulation, larger mean cell area, persistent ckit expression, incomplete nuclear condensation, and lower rates of enucleation. Setd8 knockdown did not alter ESRE proliferation or viability or result in accumulation of DNA damage. Global gene expression analyses following Setd8 knockdown demonstrated that in erythroid cells, Setd8 functions primarily as a repressor. Most notably, Gata2 expression was significantly higher in knockdown cells than in control cells and Gata2 knockdown rescued some of the maturation impairments associated with Setd8 disruption. Setd8 occupies critical regulatory elements in the Gata2 locus, and knockdown of Setd8 resulted in loss of H4K20me1 and gain of H4 acetylation at the Gata2 1S promoter. These results suggest that Setd8 is an important regulator of erythroid maturation that works in part through repression of Gata2 expression.

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“…In our analysis, we observed that hsa_circ_0001946, also known as CDR1as, is differentially regulated in early stage breast tumors. Overexpression of CDR1as decoys miR-7 with its 73 binding sites causing tumor promotion through epithelialto-mesenchymal transition, invasion and metastasis [29][30][31] . Oncogenic potential of CDR1as through miR-7 sponging has been shown in gastric cancer and carcinoma of liver, esophagus and lung 19,[32][33][34] .…”

Section: Discussionmentioning

confidence: 99%

RNA sequencing identifies dysregulated circular RNAs in early-stage breast cancer

Arvinden

Kuha

Meenakumari

et al. 2018

Preprint

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Background: Breast cancer is a major cause of cancer related death in women worldwide.Molecular diagnostic markers that are detectable in early-stage breast cancer can aid in effective clinical intervention. Circular RNAs are a recently identified group of non-coding RNA with potential role in cancer development and progression. In this study, we aimed to identify circular RNAs specific for early stage breast cancer. Method: Circular RNA expression profile was analyzed in early-stage breast cancer tissues (N=5), matched normal counterparts (N=5) and absolute normal samples (N=5) by RNA-sequencing that enables a comprehensive analysis of RNA expression across the transcriptome. Two different algorithms, find_circ and DCC were used to identify the differentially expressed circular RNAs. Results: A total of 58 and 87 circular RNAs were found to be differentially expressed by find_circ and DCC algorithms, respectively, among which 26 circular RNAs were common. Hsa_circ_0001946 (CDR1-as) was found to be upregulated in early stage breast cancer along with other novel circular RNAs (hsa_circ_0008225, hsa_circ_0007766, hsa_circ_0016601). We also found that a few of the identified circular RNAs harbor microRNA binding sites which can lead to microRNA sponging activity and pre-microRNA sequences which can generate mature microRNAs. The identified circular RNAs that are differentially regulated in early stage breast cancer can be of potential diagnostic/prognostic importance. Conclusion: Circular RNA are differentially expressed in the early-stage breast cancer with potential application in early diagnosis and prognosis. The differentially expressed circular RNA can sequester microRNA and can act as microRNA precursor as well.Keywords circular RNA; non-coding RNA; breast cancer; circRNA-microRNA interaction; circRNA as miRNA precursor

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microRNA-7 Suppresses the Invasive Potential of Breast Cancer Cells and Sensitizes Cells to DNA Damages by Targeting Histone Methyltransferase SET8

Cited by 46 publications

References 51 publications

Long non-coding RNA XLOC_006390 promotes cervical cancer proliferation and metastasis through the regulation of SET domain containing 8

Long non-coding RNA XLOC_006390 promotes cervical cancer proliferation and metastasis through the regulation of SET domain containing 8

Histone Methyltransferase Setd8 Represses Gata2 Expression and Regulates Erythroid Maturation

RNA sequencing identifies dysregulated circular RNAs in early-stage breast cancer

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