Circular RNAs in acute myeloid leukemia

AbstractAlthough mechanistic studies clarifying the molecular underpinnings of AML have facilitated the development of several novel targeted therapeutics, most AML patients still relapse. Thus, overcoming the inherent and acquired resistance to current therapies remains an unsolved clinical problem. While current diagnostic modalities are primarily defined by gross morphology, cytogenetics, and to an extent, by deep targeted gene sequencing, there is an ongoing demand to identify newer diagnostic, therapeutic and prognostic biomarkers for AML. Recent interest in exploring the role of circular RNA (circRNA) in elucidating AML biology and therapy resistance has been promising. This review discerns the circular RNAs’ evolving role on the same scientific premise and attempts to identify its potential in managing AML.

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Hsa_circ_0026628 promotes the development of colorectal cancer by targeting SP1 to activate the Wnt/β-catenin pathway

Cell Death and Disease ◽

10.1038/s41419-021-03794-6 ◽

2021 ◽

Vol 12 (9) ◽

Author(s):

Xuexiu Zhang ◽

Jianning Yao ◽

Haoling Shi ◽

Bing Gao ◽

Haining Zhou ◽

...

Keyword(s):

Colorectal Cancer ◽

Transcription Factor ◽

Circular Rna ◽

Luciferase Reporter ◽

Circular Rnas ◽

Transcriptional Level ◽

Sp1 Transcription Factor ◽

Reporter Assays ◽

Sphere Formation

AbstractCircular RNAs (circRNAs) have been reported to play crucial roles in the progression of various cancers, including colorectal cancer (CRC). SP1 (Sp1 transcription factor) is a well-recognized oncogene in CRC and is deemed to trigger the Wnt/β-catenin pathway. The present study was designed to investigate the role of circRNAs which shared the same pre-mRNA with SP1 in CRC cells. We identified that hsa_circ_0026628 (circ_0026628), a circular RNA that originated from SP1 pre-mRNA, was upregulated in CRC cells. Sanger sequencing and agarose gel electrophoresis verified the circular characteristic of circ_0026628. Functional assays including CCK-8, colony formation, transwell, immunofluorescence staining, and sphere formation assay revealed the function of circ_0026628. RNA pull-down and mass spectrometry disclosed the proteins interacting with circ_0026628. Mechanistic assays including RIP, RNA pull-down, CoIP, ChIP, and luciferase reporter assays demonstrated the interplays between molecules. The results depicted that circ_0026628 functioned as a contributor to CRC cell proliferation, migration, EMT, and stemness. Mechanistically, circ_0026628 served as the endogenous sponge of miR-346 and FUS to elevate SP1 expression at the post-transcriptional level, thus strengthening the interaction between SP1 and β-catenin to activate the Wnt/β-catenin pathway. In turn, the downstream gene of Wnt/β-catenin signaling, SOX2 (SRY-box transcription factor 2), transcriptionally activated SP1 and therefore boosted circ_0026628 level. On the whole, SOX2-induced circ_0026628 sponged miR-346 and recruited FUS protein to augment SP1, triggering the downstream Wnt/β-catenin pathway to facilitate CRC progression.

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Circular RNA hsa_circ_0043280 inhibits cervical cancer tumor growth and metastasis via miR-203a-3p/PAQR3 axis

Cell Death and Disease ◽

10.1038/s41419-021-04193-7 ◽

2021 ◽

Vol 12 (10) ◽

Author(s):

Chunyu Zhang ◽

Pan Liu ◽

Jiaming Huang ◽

Yuandong Liao ◽

Chaoyun Pan ◽

...

Keyword(s):

Cervical Cancer ◽

Tumor Growth ◽

Poor Prognosis ◽

Prognostic Biomarker ◽

Circular Rna ◽

Circular Rnas ◽

Inhibit Tumor Growth ◽

Cancer Tumor ◽

Tumor Growth And Metastasis

AbstractCircular RNAs (circRNAs) are known to act as key regulators in a variety of malignancies. However, the role of circRNAs in cervical cancer (CCa) remains largely unknown. Herein, we demonstrated that a circRNA derived from the TADA2A gene (hsa_circ_0043280) was significantly downregulated in CCa and that this reduction in expression was correlated with a poor prognosis. Furthermore, our results demonstrated that hsa_circ_0043280 functions as a tumor suppressor to inhibit tumor growth and metastasis in CCa. Mechanistically, hsa_circ_0043280 competitively sponges miR-203a-3p and prevents miR-203a-3p from reducing the levels of PAQR3. Collectively, our results demonstrate that hsa_circ_0043280 plays a pivotal role in the development and metastasis of CCa, thus suggesting that hsa_circ_0043280 has significant potential as a prognostic biomarker and a therapeutic target for CCa.

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The role of exosomes and MYC in therapy resistance of acute myeloid leukemia: Challenges and opportunities

Molecular Aspects of Medicine ◽

10.1016/j.mam.2019.10.001 ◽

2019 ◽

Vol 70 ◽

pp. 21-32 ◽

Cited By ~ 6

Author(s):

Nithya Mudgapalli ◽

Palanisamy Nallasamy ◽

Haritha Chava ◽

Srinivas Chava ◽

Anup S. Pathania ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Therapy Resistance ◽

Challenges And Opportunities ◽

Acute Myeloid

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Circular RNA Expression: Its Potential Regulation and Function in Abdominal Aortic Aneurysms

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/9934951 ◽

2021 ◽

Vol 2021 ◽

pp. 1-21

Author(s):

Yanshuo Han ◽

Hao Zhang ◽

Ce Bian ◽

Chen Chen ◽

Simei Tu ◽

...

Keyword(s):

Molecular Mechanisms ◽

Human Life ◽

Abdominal Aortic Aneurysms ◽

Circular Rna ◽

Aortic Aneurysms ◽

Current Evidence ◽

Circular Rnas ◽

Regulatory Pathways ◽

Abdominal Aortic

Abdominal aortic aneurysms (AAAs) have posed a great threat to human life, and the necessity of its monitoring and treatment is decided by symptomatology and/or the aneurysm size. Accumulating evidence suggests that circular RNAs (circRNAs) contribute a part to the pathogenesis of AAAs. circRNAs are novel single-stranded RNAs with a closed loop structure and high stability, having become the candidate biomarkers for numerous kinds of human disorders. Besides, circRNAs act as molecular “sponge” in organisms, capable of regulating the transcription level. Here, we characterize that the molecular mechanisms underlying the role of circRNAs in AAA development were further elucidated. In the present work, studies on the biosynthesis, bibliometrics, and mechanisms of action of circRNAs were aims comprehensively reviewed, the role of circRNAs in the AAA pathogenic mechanism was illustrated, and their potential in diagnosing AAAs was examined. Moreover, the current evidence about the effects of circRNAs on AAA development through modulating endothelial cells (ECs), macrophages, and vascular smooth muscle cells (VSMCs) was summarized. Through thorough investigation, the molecular mechanisms underlying the role of circRNAs in AAA development were further elucidated. The results demonstrated that circRNAs had the application potential in the diagnosis and prevention of AAAs in clinical practice. The study of circRNA regulatory pathways would be of great assistance to the etiologic research of AAAs.

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Identification of circular RNA hsa_circ_0044556 and its effect on the progression of colorectal cancer

10.21203/rs.3.rs-26944/v2 ◽

2020 ◽

Author(s):

Liang Jing ◽

Junhui Wu ◽

Xiaocheng Tang ◽

Min Ma ◽

Fei Long ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Lines ◽

Tumor Stage ◽

Circular Rna ◽

Gene Expression Omnibus ◽

Migration And Invasion ◽

Circular Rnas ◽

Normal Tissues ◽

Node Metastasis

Abstract Background: Circular RNAs (circRNAs) are a novel class of noncoding RNAs. Increasing evidence indicates that circRNAs play an important role in the occurrence and development of tumors. However, the role of circRNA hsa_circ_0044556 in the progression of colorectal cancer (CRC) remains unclear. Methods: First, we searched for differentially expressed circRNAs using a circRNA microarray in paired CRC and adjacent normal tissues. The circRNA hsa_circ_0044556 was screened out from the existing CRC circRNA microarray in the Gene Expression Omnibus database and our microarray. The clinical significance of hsa_circ_0044556 expression level in CRC patients was then investigated. Finally, the functions of the targets of this circRNA were determined in CRC cell lines.Results:Hsa_circ_0044556 was highly expressed in CRC patients and was positively correlated with tumor stage and lymph node metastasis. In CRC cell lines, the proliferation, migration, and invasion of cancer cells were inhibited by knocking down hsa_circ_0044556 expression.Conclusion: Hsa_circ_0044556 promoted the progression of CRC. It is possible that hsa_circ_0044556 will become a novel biomarker or therapeutic target for CRC.

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Circular RNA hsa_circ_0081343 promotes trophoblast cell migration and invasion and inhibits trophoblast apoptosis by regulating miR-210-5p/DLX3 axis

10.21203/rs.3.rs-361692/v1 ◽

2021 ◽

Author(s):

Jiansheng Xie ◽

Hui Wang ◽

Caiqun Luo ◽

Xiaoxia Wu ◽

Jianming Zhang ◽

...

Keyword(s):

Luciferase Activity ◽

Circular Rna ◽

Extravillous Trophoblast ◽

Migration And Invasion ◽

Circular Rnas ◽

Protein Levels ◽

Apoptosis Protein ◽

Luciferase Activity Assay ◽

Rna Immunoprecipitation

Abstract Background: Various circular RNAs (circRNAs) are dysregulated in the placenta of fetal growth restriction fetuses, but their role and regulatory mechanisms have not been fully elucidated. Herein, we aimed to elucidate the role of hsa_circ_0081343 in regulating the migration, invasion, and apoptosis in the human extravillous trophoblast HTR-8 cells.Methods: circRNA and miRNA levels were examined using quantitative real-time PCR (RT-PCR). Overexpression plasmid constructs and siRNA were used to overexpress and knockdown hsa_circ_0081343, respectively. Transwell assay and flow cytometry analysis were performed to evaluate the effect of hsa_circ_0081343 or miR-210-5p on migration, invasion, and apoptosis. Protein levels were analyzed using western blot. Dual luciferase activity assay and anti-AGO2 RNA immunoprecipitation (RIP) assays were performed to identify the relationship between miR-210-5p and hsa_circ_0081343.Results: Hsa_circ_0081343 expression was significantly downregulated in 37 FGR placental tissues as compared to healthy placental control tissues. Hsa_circ_0081343 overexpression possibly inhibits apoptosis by downregulating the expression of cleaved caspase 3 and caspase 9 and alleviates the migration and invasion of HTR-8 cells by inducing the expression of MMP2 and MMP9. The dual luciferase activity and anti-AGO2 RIP assay results showed that hsa_circ_0081343 binds to miR-210-5p. miR-210-5p overexpression eliminated the effect of hsa_circ_0081343 overexpression in HTR-8 cells. Finally, DLX3 was identified as a direct target of miR-210-5p. Conclusions: Hsa_circ_0081343 regulates the migration, invasion, and apoptosis of HTR-8 cells via the hsa-miR-210-5p/DLX3 axis. Thus, hsa_circ_0081343 plays a key role in the etiology and pathogenesis of FGR implicating its importance as a novel candidate for targeted FGR therapy.

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Role of Differentially Expressed Proteins in Acquired Resistance to Cdk4/6 Inhibitor in Breast Cancer

10.21203/rs.3.rs-556331/v1 ◽

2021 ◽

Author(s):

Binayak Kumar ◽

Peeyush Prasad ◽

Ragini Singh ◽

Ram Krishana Sahu ◽

Ashutosh Singh ◽

...

Keyword(s):

Breast Cancer ◽

Drug Targets ◽

Acquired Resistance ◽

Therapy Resistance ◽

Resistant Cell ◽

Molecular Signature ◽

Mcf 7 ◽

Resistant Cells

Abstract CDK4/6 inhibitors (Abemaciclib, Ab and Palbociclib, Pb) stop the G1-phase in cell-cycle being used to cure advanced stage of breast cancer (BC). Acquired resistance is a major challenge in BC therapy. The molecular signature of the therapy resistance for Ab and Pb drugs in BC should be explored. Here, we developed Ab/Pb-resistant cell-models and explored the molecular changes. Drug’s resistance cells were developed in MCF-7 cells by continuous drug treatment and it was confirmed by MTT-assay, PI-staining-microscopy, and real-time-qPCR. Global proteome profiling done by Labelled-free-Proteome-Orbitrap-Fusion-MS-MS technique. Bioinformatics tools used to analyse the proteome data. Ab-resistant and Pb-resistant MCF-7 cells showed increased tolerance for the respective drug. The BCL-2 and MCL-1 survival genes were up-regulated, while the apoptosis genes BAD, BAX, CASP-3 and PARP-1were down-regulated in the resistant cells. Expression of the MDR-1, ABCG2, ESR-1, CDK4, CDK6, and Cyclin-D1 genes were increased in both resistance cells. For proteomics, 237 and 239 proteins were expressed differently in the resistant Ab and Pb cells, respectively. The NUDT5, PEPD, ABAT, ATP1B1, GGCT, and SELENBP1 proteins were down-regulated and the SBSN, HSD17B10, CD9, PDIA3, PSMB4, SLC2A1, and VTN proteins were up-regulated in Ab-resistant cells. The NUDT5, PEPD, and GGCT proteins were down-regulated, while CD47, HIST1H2BN, LMNA, VTN, PSMB5, HBB, PSMA7, FLNB, PRDX4, VDAC1, GOT2, HSPA5, SERPINH1, EIF4A2, FTH, and VIM proteins were up-regulated in Pb-resistant cells. These proteins are a new set of prognostic markers and drug targets for overcoming the respective drug resistance. However, it is necessary to perform an in vivo or clinical assessment.

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CircMYOF triggers progression and facilitates glycolysis via the VEGFA/PI3K/AKT axis by absorbing miR-4739 in pancreatic ductal adenocarcinoma

Cell Death Discovery ◽

10.1038/s41420-021-00759-8 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Dandan Zheng ◽

Xianxian Huang ◽

Juanfei Peng ◽

Yanyan Zhuang ◽

Yuanhua Li ◽

...

Keyword(s):

Glucose Metabolism ◽

Pancreatic Ductal Adenocarcinoma ◽

Circular Rna ◽

Ductal Adenocarcinoma ◽

Luciferase Reporter ◽

Circular Rnas ◽

Loss Of Function ◽

Competing Endogenous Rna ◽

Rnase R

AbstractEmerging evidence has demonstrated that circular RNAs (circRNAs) take part in the initiation and development of pancreatic ductal adenocarcinoma (PDA), a deadly neoplasm with an extremely low 5-year survival rate. Reprogrammed glucose metabolism is a key feature of tumour development, including PDA. In this research, we evaluated the role of circRNAs in reprogrammed glucose metabolism in PDA. RNA sequencing under various glucose incubation circumstances was performed. A new circMYOF was identified. Sanger sequencing and RNase R treatment confirmed its circular RNA characteristics. Real-time PCR indicated that it was highly expressed in PDA clinical specimens and cell lines. Gain-of- and loss-of-function assays showed that circMYOF induced progression in PDA. Mechanistically, RNA pull-down and luciferase reporter experiments elucidated that circMYOF, as a competing endogenous RNA for miR-4739, facilitated glycolysis via the VEGFA/PI3K/AKT pathway. Taken together, our findings indicate that circMYOF may work as a desirable biomarker and therapeutic target for PDA patients.

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Epigenetic modifications in acute myeloid leukemia: The emerging role of circular RNAs (Review)

International Journal of Oncology ◽

10.3892/ijo.2021.5287 ◽

2021 ◽

Vol 59 (6) ◽

Author(s):

Mohammed Issah ◽

Dansen Wu ◽

Feng Zhang ◽

Weili Zheng ◽

Yanquan Liu ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Epigenetic Modifications ◽

Circular Rnas ◽

Acute Myeloid

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The Regulation of circRNA RNF13/miRNA-1224-5p Axis Promotes the Malignant Evolution in Acute Myeloid Leukemia

BioMed Research International ◽

10.1155/2020/5654380 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Rong Zhang ◽

Yingchun Li ◽

Hongtao Wang ◽

Ke Zhu ◽

Guojun Zhang

Keyword(s):

Cell Cycle ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Circular Rna ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Tenascin C ◽

Qrt Pcr ◽

Acute Myeloid

Objective. To study the biological function of circular RNA RNF13 (circRNF13) in acute myeloid leukemia (AML) and its relationship with prognosis. Methods. We constructed stable AML cell lines with downregulated expression of circRNF13, and then, we explored the effect of downregulation of circRNF13 expression on the proliferation, migration, and invasion through qRT-PCR, MTT curve, colony formation, transwell migration and invasion experiment, cell cycle, apoptosis, Caspase 3/7 assay, and other experiments. We also studied the expression of C-myc and Tenascin-C by qRT-PCR to explore the role of circRNF13. Results. When the expression of circRNF13 was downregulated, the proliferation rate of AML cells decreased significantly, the cell cycle was blocked to G1 phase, and apoptosis rate increased significantly. C-myc related to cell proliferation decreased significantly at RNA level. Furthermore, when the expression of circRNF13 was downregulated, the migration and invasion ability of AML cells was significantly reduced, and the expression of Tenascin-C related to migration and invasion also decreased significantly. The luciferase reporter assay system confirmed that miRNA-1224-5p was the direct target of circRNF13. Conclusion. CircRNF13 inhibited the proliferation, migration, and invasion of AML cells by regulating the expression of miRNA-1224-5p. This study provides some clues for the diagnosis and treatment of AML.

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