A SUV39H1-low chromatin state characterises and promotes migratory properties of cervical cancer cells

Rodrigues, Calvin; Pattabiraman, Chitra; Vijaykumar, Anjali; Arora, Reety; Narayana, Suma Mysore; Kumar, Rekha V.; Notani, Dimple; Varga‐Weisz, Patrick; Krishna, Sudhir

doi:10.1016/j.yexcr.2019.02.010

Cited by 14 publications

(7 citation statements)

References 30 publications

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“…To better understand how HAC mis-segregation develops over time following H3K9me3 depletion, we analyzed a time-course of tethering, focusing on centromeric proteins. We used JMJD2D K9Low cells, which present robust centromere activity that is comparable to that seen in JMJD2D K9Hi , while allowing us to study centromere behavior in an H3K9me3-low environment similar to that present in some cancer cells ( Nizialek et al, 2016 ; Rodrigues et al, 2019 ; Slee et al, 2011 ).…”

Section: Resultsmentioning

confidence: 99%

H3K9me3 maintenance on a human artificial chromosome is required for segregation but not centromere epigenetic memory

Martins

Cisneros-Soberanis

Pesenti

et al. 2020

Journal of Cell Science

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Most eukaryotic centromeres are located within heterochromatic regions. Paradoxically, heterochromatin can also antagonize de novo centromere formation, and some centromeres lack it altogether. In order to investigate the importance of heterochromatin at centromeres, we used epigenetic engineering of a synthetic alphoidtetO human artificial chromosome (HAC), to which chimeric proteins can be targeted. By tethering the JMJD2D demethylase (also known as KDM4D), we removed heterochromatin mark H3K9me3 (histone 3 lysine 9 trimethylation) specifically from the HAC centromere. This caused no short-term defects, but long-term tethering reduced HAC centromere protein levels and triggered HAC mis-segregation. However, centromeric CENP-A was maintained at a reduced level. Furthermore, HAC centromere function was compatible with an alternative low-H3K9me3, high-H3K27me3 chromatin signature, as long as residual levels of H3K9me3 remained. When JMJD2D was released from the HAC, H3K9me3 levels recovered over several days back to initial levels along with CENP-A and CENP-C centromere levels, and mitotic segregation fidelity. Our results suggest that a minimal level of heterochromatin is required to stabilize mitotic centromere function but not for maintaining centromere epigenetic memory, and that a homeostatic pathway maintains heterochromatin at centromeres.This article has an associated First Person interview with the first authors of the paper.

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Section: Resultsmentioning

confidence: 99%

H3K9me3 maintenance on a human artificial chromosome is required for segregation but not centromere epigenetic memory

Martins

Cisneros-Soberanis

Pesenti

et al. 2020

Journal of Cell Science

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“…BMP4 expression has been shown to be negatively regulated by Smad9 [17]. Further evidence has suggested that SUV39H1 exerts a suppressive effect on Smad9 expression [16]. Moreover, the expression of BMP4 is higher in NSCLC tumors than that in paired adjacent non-tumor tissues [24].…”

Section: Discussionmentioning

confidence: 99%

“…SUV39H1 has been reported to inhibit the expression of Smad9 [16], which has been shown to suppress the expression of BMP4 [17]. Moreover, BMP4 has been documented to promote the initiation of NSCLC [18] and is highly expressed in NSCLC tumor tissues [24].…”

Section: Suv39h1 Regulates the Expression Of Smad9/bmp4 In Vitromentioning

confidence: 99%

“…A recent study has shown that silencing SUV39H1 led to elevated NSCLC cell proliferation, migration, and survival [15]. On the other hand, reduced expression of SUV39H1 is associated with upregulation of Smad9 [16], a negative regulator of bone morphogenetic protein 4 (BMP4) [17]. Notably, recent evidence has suggested that BMP4 promotes the tumorigenesis of NSCLC [18].…”

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confidence: 99%

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Reduction of miR-744 delivered by NSCLC cell-derived extracellular vesicles upregulates SUV39H1 to promote NSCLC progression via activation of the Smad9/BMP9 axis

Gao

Tian

et al. 2021

J Transl Med

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Background Non-small cell lung cancer (NSCLC) is a common type of lung cancer. Extracellular vehicles (EVs) are nano-sized particles containing proteins, lipids, and miRNAs secreted by various cells, which play important roles in the development of lung cancer by regulating a wide range of signaling pathways. This study focused on elucidating a potential mechanism by which EVs promote the development of NSCLC. Methods Expression levels of miR-744, SUV39H1, Smad9, and BMP4 in clinical tissue samples of NSCLC patients and cell lines were quantified by RT-qPCR and/or western blot analysis. The interaction between SUV39H1 and miR-744 was identified by dual-luciferase reporter assay. miR-744, SUV39H1, and BMP4 expression levels were modulated in A549 and H460 cells, in order to evaluate their effects on cell proliferation, colony formation and cell cycle. A NSCLC xenograft mouse model was used to verify the in vitro findings. NSCLC cell-derived EVs and normal bronchial epithelial cell-derived EVs were isolated and their roles in NSCLC development were evaluated in vivo and in vitro. Results miR-744 expression was lower in cancer cell-derived derived EVs than in normal lung epithelial cell-derived EVs. Reduced miR-744 expression in EVs upregulated SUV39H1 in NSCLC cells and further increased BMP4 levels to promote NSCLC development. BMP4 was upregulated in NSCLC cells upon suppression of Smad9 mediated by SUV39H1. Reduced miR-744 expression transferred from cancer cell-derived EVs into NSCLC cells enhanced cancer development. Conclusion Overall, our findings unveiled a mechanism whereby miR-744 delivered by NSCLC-derived EVs upregulated SUV39H1, activating the Smad9/BMP9 axis and thus promoted cancer development.

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“…In malignant brain glioma, tumors can be suppressed by repressive targets of SUV39H1 [33] . However, in cervical cancer, the weak chromatin state of SUV39H1 promotes cell migration; thus, SUV39H1 might be a novel and critical target for epigenetic therapies [34] . In our study, we found that SUV39H1 expression was higher in DLBCL than in other kinds of solid tumors regardless of the tissue or cell type by searching the GEPIA and CCLE databases and verifying our results pathologically.…”

Section: Discussionmentioning

confidence: 99%

Clinical expression and prognosis of SUV39H1 in diffuse large B-cell lymphoma

Zhang¹,

Wen²,

Lei³

et al. 2021

Preprint

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Background: Epigenetic regulation plays vital roles in the oncogenesis and treatment of diffuse large B-cell lymphoma (DLBCL). The H3K9me3-specific histone methyltransferase SUV39H1 is an epigenetic gene that promotes the progression of a variety of malignancies. However, the roles of SUV39H1 in DLBCL remain unclear.Methods: Initially, the Oncomine, Cancer Cell Line Encyclopedia (CCLE), UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) databases were searched to explore the expression of SUV39H1 in DLBCL. The clinical parameters and pathological sections of 61 successive patients, including 47 cases of DLBCL and 14 cases of reactive lymphoid hyperplasia, were collected from January 2019 to November 2020. Immunohistochemistry was conducted to verify the results of the database search. Finally, relevant parameters and pathological results were combined to analyze the expression of SUV39H1.Results: We found that the expression of SUV39H1 in DLBCL tissues was higher than that in normal and other cancer tissues (P<0.05) in database and immunohistochemistry analyses. Among the analyzed clinical parameters, only tumor size was closely associated with SUV39H1 (P=0.037), suggesting that patients with high SUV39H1 expression are less likely to develop tumors over 7.5 cm in size. Regarding survival, the group with high SUV39H1 expression had a lower survival rate than the group with low SUV39H1 expression in terms of 10-year disease-free survival (DFS) according to the database analyses (P=0.035). However, SUV39H1 was revealed as an independent predictor of overall survival (OS) and progression-free survival (PFS) in patients from both databases and our hospital (P>0.05).Conclusion: SUV39H1 expression is higher in DLBCL tissues than in normal and other cancer tissues, indicating that DLBCL patients may not develop bulky tumors over follow-up and suggesting that SUV39H1 might serve not only as a predictive factor in the clinic but also as a target for the epigenetic therapy of DLBCL.

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A SUV39H1-low chromatin state characterises and promotes migratory properties of cervical cancer cells

Cited by 14 publications

References 30 publications

H3K9me3 maintenance on a human artificial chromosome is required for segregation but not centromere epigenetic memory

H3K9me3 maintenance on a human artificial chromosome is required for segregation but not centromere epigenetic memory

Reduction of miR-744 delivered by NSCLC cell-derived extracellular vesicles upregulates SUV39H1 to promote NSCLC progression via activation of the Smad9/BMP9 axis

Clinical expression and prognosis of SUV39H1 in diffuse large B-cell lymphoma

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