CCNE1 and BRD4 co-amplification in high-grade serous ovarian cancer is associated with poor clinical outcomes

Petersen, Shariska; Wilson, Andrew J.; Hirst, Jeff; Roby, Katherine F.; Fadare, Oluwole; Crispens, Marta A.; Beeghly–Fadiel, Alicia; Khabele, Dineo

doi:10.1016/j.ygyno.2020.01.038

“…BRD4 was regulated by circ_0007841/miR-338-3p axis in MM cells. High expression of BRD4 promoted the progression of high-grade serous ovarian cancer [34]. Besides, BRD4 was found to be a target of H19/miR-152-3p axis to promote the progression of MM [21].…”

Section: Discussionmentioning

confidence: 96%

Circ_0007841 promotes the progression of multiple myeloma through targeting miR-338-3p/BRD4 signaling cascade

Wang

¹

,

Lin

²

,

Song

³

et al. 2020

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Background: The pathogenesis of multiple myeloma (MM) is not completely known. Uncovering the potential mechanism of MM initiation and progression is essential for identifying novel diagnostic and therapeutic targets. Herein, we explored the function and the working mechanism of circular RNA circ_0007841 in MM progression. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the expression of circ_0007841, microRNA-338-3p (miR-338-3p) and bromodomain containing 4 (BRD4). Cell proliferation ability was analyzed through cell counting kit-8 (CCK8) assay, colony formation assay and flow cytometry. Transwell assays were conducted to measure the migration and invasion abilities of MM cells. Cell apoptosis was also assessed by flow cytometry. The interaction between miR-338-3p and circ_0007841 or BRD4 was confirmed by dual-luciferase reporter assay and RNA-pull down assay. Results: Circ_0007841 was highly expressed in bone marrow (BM)-derived plasma cells of MM patients and MM cell lines than that in healthy volunteers and normal plasma cell line nPCs. Circ_0007841 promoted the proliferation, cell cycle and metastasis and impeded the apoptosis of MM cells. miR-338-3p was a direct target of circ_0007841 in MM cells and circ_0007841 accelerated the progression of MM through targeting miR-338-3p. BRD4 could directly bind to miR-338-3p in MM cells and miR-338-3p exerted an anti-tumor role through targeting BRD4. Circ_0007841 promoted the activation of PI3K/AKT signaling via miR-338-3p/BRD4 axis. Exosomes generated from mesenchymal stromal cells (MSCs) elevated the malignant behaviors of MM cells via circ_0007841. Conclusion: Circ_0007841 acted as an oncogene to promote the proliferation, cell cycle and motility and restrain the apoptosis of MM cells through sequestering miR-338-3p to up-regulate the expression of BRD4.

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“…High expression of BRD4 promoted the progression of high-grade serous ovarian cancer [34]. Besides, BRD4 was found to be a target of H19/miR-152-3p axis to promote the progression of MM [21].…”

Section: Discussionmentioning

confidence: 96%

Circ_0007841 promotes the progression of multiple myeloma through targeting miR-338-3p/BRD4 signaling cascade

Wang

¹

,

Lin

²

,

Song

³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: The pathogenesis of multiple myeloma (MM) is not completely known. Uncovering the potential mechanism of MM initiation and progression is essential for identifying novel diagnostic and therapeutic targets. Herein, we explored the function and the working mechanism of circular RNA circ_0007841 in MM progression. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the expression of circ_0007841, microRNA-338-3p (miR-338-3p) and bromodomain containing 4 (BRD4). Cell proliferation ability was analyzed through cell counting kit-8 (CCK8) assay, colony formation assay and flow cytometry. Transwell assays were conducted to measure the migration and invasion abilities of MM cells. Cell apoptosis was also assessed by flow cytometry. The interaction between miR-338-3p and circ_0007841 or BRD4 was confirmed by dual-luciferase reporter assay and RNA-pull down assay. Results: Circ_0007841 was highly expressed in bone marrow (BM)-derived plasma cells of MM patients and MM cell lines than that in healthy volunteers and normal plasma cell line nPCs. Circ_0007841 promoted the proliferation, cell cycle and metastasis and impeded the apoptosis of MM cells. miR-338-3p was a direct target of circ_0007841 in MM cells and circ_0007841 accelerated the progression of MM through targeting miR-338-3p. BRD4 could directly bind to miR-338-3p in MM cells and miR-338-3p exerted an anti-tumor role through targeting BRD4. Circ_0007841 promoted the activation of PI3K/AKT signaling via miR-338-3p/BRD4 axis. Exosomes generated from mesenchymal stromal cells (MSCs) elevated the malignant behaviors of MM cells via circ_0007841. Conclusion: Circ_0007841 acted as an oncogene to promote the proliferation, cell cycle and motility and restrain the apoptosis of MM cells through sequestering miR-338-3p to up-regulate the expression of BRD4.

show abstract

“…BRD4 was regulated by circ_0007841/miR-338-3p axis in MM cells. High expression of BRD4 promoted the progression of high-grade serous ovarian cancer [34].…”

Section: Discussionmentioning

confidence: 99%

Circ_0007841 promotes the progression of multiple myeloma via miR-338-3p/BRD4 axis

Wang

¹

,

Lin

²

,

Song

³

et al. 2020

Preprint

0

View full text Add to dashboard Cite

Background The pathogenesis of multiple myeloma (MM) is not completely known. Herein, we explored the function and the working mechanism of circular RNA circ_0007841 in MM progression. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect the expression of circ_0007841, microRNA-338-3p (miR-338-3p) and bromodomain containing 4 (BRD4). The proliferation and metastasis of MM cells were examined by cell counting kit-8 (CCK8) assay and transwell assays. Flow cytometry was conducted to assess the cell cycle and the apoptosis of MM cells. The targets of circ_0007841 and miR-338-3p were predicted by circinteractome and targetscan softwares, and these predictions were confirmed by dual-luciferase reporter assay and RNA-pull down assay. The protein levels of BRD4, phosphorylated-phosphatidylinositol 3-kinase (p-PI3K), PI3K, p-AKT serine/threonine kinase (p-AKT) and AKT were measured by Western blot assay. Exosomes were extracted using Exosome isolation kit. Results Circ_0007841 was highly expressed in bone marrow (BM)-derived plasma cells of MM patients and MM cells than that in healthy volunteers and normal plasma cells nPCs. Circ_0007841 promoted the proliferation, cell cycle and metastasis and impeded the apoptosis of MM cells. MiR-338-3p was a direct target of circ_0007841 in MM cells. Circ_0007841 accelerated the progression of MM through targeting miR-338-3p. BRD4 could directly bind to miR-338-3p in MM cells. MiR-338-3p exerted an anti-tumor role through targeting BRD4. Circ_0007841 promoted the activation of PI3K/AKT signaling via miR-338-3p/BRD4 axis. Exosomes generated from mesenchymal stromal cells (MSCs) elevated the malignant behaviors of MM cells via circ_0007841. Conclusion Circ_0007841 acted as an oncogene to promote the proliferation, cell cycle and motility and restrain the apoptosis of MM cells through sequestering miR-338-3p to up-regulate the expression of BRD4.

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CCNE1 and BRD4 co-amplification in high-grade serous ovarian cancer is associated with poor clinical outcomes

Cited by 39 publications

References 30 publications

Circ_0007841 promotes the progression of multiple myeloma through targeting miR-338-3p/BRD4 signaling cascade

Circ_0007841 promotes the progression of multiple myeloma through targeting miR-338-3p/BRD4 signaling cascade

Circ_0007841 promotes the progression of multiple myeloma through targeting miR-338-3p/BRD4 signaling cascade

Circ_0007841 promotes the progression of multiple myeloma via miR-338-3p/BRD4 axis

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