circASXL1-1 regulates BAP1 deubiquitinase activity in leukemia

Jadhav, Shweta; Nishi, Kumari; Ng, Larry; Tan, Pei Fang; Yeo-Teh, Nicole Shu Ling; Goh, Yufen; Fam, Wee Nih; Tng, Jia Qi; Tian, Johann Shane; Koh, Bryan T. H.; Chun, Chan Ming; Wang, Wilson; Chng, Wee Joo; Fullwood, Melissa J.; Guccione, Ernesto; Karnani, Neerja; Tenen, Daniel G.; Jha, Sudhakar

doi:10.3324/haematol.2019.225961

Cited by 9 publications

(7 citation statements)

References 15 publications

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“…CircRNAs are closely related to myeloid malignancies. For example, circRNA-DLEU2 inhibits miR-496 and upregulates PRKACB expression, thus accelerating AML progression [ 18 ]; a circRNA derived from MYBL2 promotes FMS-like tyrosine kinase-3 translation by increasing polypyrimidine tract binding protein 1 expression, leading to a poor prognosis [ 19 ]; circASXL1-1-mediated regulation of BAP1 deubiquitinase activity might be a promising therapeutic option for myeloid leukaemia [ 20 ]. Our previous studies also confirmed that circRNAs may play an important role in regulating intercellular crosstalk in EMI, and we also found that PLXNB2 predicted a poor prognosis of patients with AML and might be involved in EMI regulation [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

A circular RNA derived from PLXNB2 as a valuable predictor of the prognosis of patients with acute myeloid leukaemia

Wang

Bian

et al. 2021

J Transl Med

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Background As a common haematological malignancy, acute myeloid leukaemia (AML), particularly with extramedullary infiltration (EMI), often results in a high mortality rate and poor prognosis. Circular RNAs (circRNAs) regulate biological and pathogenic processes, suggesting a potential role in AML. We have previously described the overall alterations in circRNAs and their regulatory networks between patients with AML presenting with and without EMI. This study aims to find new prognostic and therapeutic targets potentially associated with AML. Methods qRT-PCR was performed on samples from 40 patients with AML and 15 healthy controls. The possibility of using circPLXNB2 (circRNA derived from PLXNB2) as a diagnostic and prognostic biomarker for AML was analysed with multiple statistical methods. In vitro, the function of circPLXNB2 was studied by lentivirus transfection, CCK-8 assays, flow cytometry, and Transwell experiments. Western blotting and qRT-PCR were performed to detect the expression of related proteins and genes. The distribution of circPLXNB2 in cells was observed using RNA fluorescence in situ hybridization (RNA-FISH). We also investigated the role of circPLXNB2 by establishing AML xenograft models in NOD/SCID mice. Results By analysing the results of qRT-PCR detection of clinical samples, the expression of the circPLXNB2 and PLXNB2 mRNAs were significantly increased in patients with AML, more specifically in patients with AML presenting with EMI. High circPLXNB2 expression was associated with an obviously shorter overall survival and leukaemia-free survival of patients with AML. The circPLXNB2 expression was positively correlated with PLXNB2 mRNA expression, as evidenced by Pearson’s correlation analysis. RNA-FISH revealed that circPLXNB2 is mainly located in the nucleus. In vitro and in vivo, circPLXNB2 promoted cell proliferation and migration and inhibited apoptosis. Notably, circPLXNB2 also increased the expression of PLXNB2, BCL2 and cyclin D1, and reduced the expression of BAX. Conclusion In summary, we validated the high expression of circPLXNB2 and PLXNB2 in patients with AML. Elevated circPLXNB2 levels were associated with poor clinical outcomes in patients with AML. Importantly, circPLXNB2 accelerated tumour growth and progression, possibly by regulating PLXNB2 expression. Our study highlights the potential of circPLXNB2 as a new prognostic predictor and therapeutic target for AML in the future.

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Section: Introductionmentioning

confidence: 99%

A circular RNA derived from PLXNB2 as a valuable predictor of the prognosis of patients with acute myeloid leukaemia

Wang

Bian

et al. 2021

J Transl Med

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“…Jadhav et al identified circASXL1-1 and circASXL1-2 from the SXL1 gene locus in the THP-1 leukemic cell line, which were also expressed in various cell lines. Furthermore, this study suggested that circASXL1-1 possibly changed the activity of the PR-BUB complex by physically associating with BAP1 and might influence the differentiation of HSCs in the myeloid lineage [105]. Overall, HSCs have shown promising clinical applications, targeting circRNAs of HSCs may contribute to a better treatment of hematologic diseases.…”

Section: Circrnas In Hematopoietic Stem Cellsmentioning

confidence: 77%

Circular RNAs in stem cells: from basic research to clinical implications

Yang

et al. 2022

Bioscience Reports

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Circular RNAs (circRNAs) are a special class of endogenous RNAs with a wide variety of pathophysiological functions via diverse mechanisms, including transcription, miRNA sponge, protein sponge/decoy, and translation. Stem cells are pluripotent cells with unique properties of self-renewal and differentiation. Dysregulated circRNAs identified in various stem cell types can affect stem cell self-renewal and differentiation potential by manipulating stemness. However, the emerging roles of circRNAs in stem cells remain largely unknown. This review summarizes the major functions and mechanisms of action of circRNAs in stem cell biology and disease progression. We also highlight circRNAs-mediated common pathways in diverse stem cell types and discuss their diagnostic significance with respect to stem cell-based therapy.

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“…CircASXL1, located in chr20:30954186-30956926 and formed by exons 2 and 3 of ASXL1, has been revealed to have correlation with both tumor stage and lymph node invasion in bladder cancer [ 37 ]. In leukemia, the low expression of circASXL1 repressed the growth of THP-1 monocytes [ 38 ]. These data suggested the oncogenic role of circASXL1 in cancer malignant progression.…”

Section: Discussionmentioning

confidence: 99%

“…These results also suggested that circASXL1 acted as a tumor promoter in CRC. As reported early, ASXL1, circASXL1 patient, has been reported to be negatively correlated with lymph node metastasis of CRC [ 38 ], and to inhibit CRC cell proliferation through acting as a target of miR-3187-3p [ 39 ], which was opposite to the function of circASXL1. Additionally, Li et al revealed that exon–intron circRNAs, located in cell nucleus, modulated their parental transcript in a cis-acting way [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

CircASXL1 knockdown represses the progression of colorectal cancer by downregulating GRIK3 expression by sponging miR-1205

Fang

Zhang

2021

World J Surg Onc

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Background Colorectal cancer (CRC) is a common aggressive tumor that poses a heavy burden to human health. An increasing number of studies have reported that circular RNA (circRNA) is involved in the progression of CRC. In this study, the special profiles of circASXL1 (circ_0001136) in CRC progression were revealed. Methods The expression of circASXL1, microRNA-1205 (miR-1205), and glutamate ionotropic receptor kainate type subunit 3 (GRIK3) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression was determined by Western blot or immunohistochemistry. Cell colony-forming ability was investigated by colony formation assay. Cell cycle and apoptosis were demonstrated using cell-cycle and cell-apoptosis analysis assays, respectively. Cell migration and invasion were detected by wound-healing and transwell migration and invasion assays, respectively. The binding sites between miR-1205 and circASXL1 or GRIK3 were predicted by circBank or miRDB online database, and identified by dual-luciferase reporter assay. The impact of circASXL1 on tumor formation in vivo was investigated by in vivo tumor formation assay. Results CircASXL1 and GRIK3 expression were apparently upregulated, and miR-1205 expression was downregulated in CRC tissues and cells relative to control groups. CircASXL1 knockdown inhibited cell colony-forming ability, migration and invasion, whereas induced cell arrest at G0/G1 phase and cell apoptosis in CRC cells; however, these effects were attenuated by miR-1205 inhibitor. Additionally, circASXL1 acted as a sponge for miR-1205, and miR-1205 was associated with GRIK3. Furthermore, circASXL1 silencing hindered tumor formation by upregulating miR-1205 and downregulating GRIK3 expression. Conclusion CircASXL1 acted an oncogenic role in CRC malignant progression via inducing GRIK3 through sponging miR-1205. Our findings provide a theoretical basis for studying circASXL1-directed therapy for CRC.

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circASXL1-1 regulates BAP1 deubiquitinase activity in leukemia

Cited by 9 publications

References 15 publications

A circular RNA derived from PLXNB2 as a valuable predictor of the prognosis of patients with acute myeloid leukaemia

A circular RNA derived from PLXNB2 as a valuable predictor of the prognosis of patients with acute myeloid leukaemia

Circular RNAs in stem cells: from basic research to clinical implications

CircASXL1 knockdown represses the progression of colorectal cancer by downregulating GRIK3 expression by sponging miR-1205

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