scholarly journals LINC00511 exacerbated T-cell acute lymphoblastic leukemia via miR-195-5p/LRRK1 axis

2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Shengli Li ◽  
Wenwen Guo ◽  
Huayun Geng ◽  
Chao Wang ◽  
Shuige Yang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Mediated Effects ◽  
Proliferation And Apoptosis ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Series Of Experiments ◽  
Non Coding Rnas

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is a malignant disease arising from the abnormal proliferation of T lymphocyte in marrow. Long non-coding RNAs (lncRNAs) are one kind of non-coding RNAs (ncRNAs), which were reported to modulate the initiation or progression of diverse cancers. However, the role of LINC00511 in T-ALL was unknown. To figure out the function and mechanism of LINC00511 in T-ALL, a series of experiments were carried out. Based on the experimental results, we discovered that LINC00511 boosted cell proliferation and invasion, but hindered cell apoptosis in T-ALL cells. Besides, based on bio-informatics tool, miR-195-5p was selected for further exploration. Then, miR-195-5p was validated to bind with LINC00511. Hereafter, LRRK1 was testified to serve as a target gene of miR-195-5p. At last, rescue assays suggested that LRRK1 overexpression restored sh-LINC00511#1-mediated effects on cell proliferation and apoptosis. All in all, LINC00511 exacerbated T-ALL progression via miR-195-5p/LRRK1 axis, implying a potential therapeutic clue for the patients with T-ALL.

scholarly journals LINC00221 suppresses the malignancy of children acute lymphoblastic leukemia

2020 ◽  
Vol 40 (5) ◽  
Author(s):  
Man Huang ◽  
Jiajia Zheng ◽  
Yongya Ren ◽  
Jingjing Zhu ◽  
Linbing Kou ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Genetic Alterations ◽  
Ki 67 ◽  
Protein Coding ◽  
Proliferation And Apoptosis ◽  
Rna Immunoprecipitation ◽  
Non Coding Rnas

Abstract As the most common malignant disease in childhood, children acute lymphoblastic leukemia (ALL) is a heterogeneous disease caused by the accumulated genetic alterations. Long non-coding RNAs (lncRNAs) are reported as critical regulators in diseases. GEPIA database indicated that long intergenic non-protein coding RNA 221 (LINC00221) was conspicuously down-regulated in acute myeloid leukemia. However, its expression pattern in ALL has not been revealed. This work was carried out to study the role of LINC00221 in ALL cells. Quantitative real-time PCR (qRT-PCR) quantified LINC00221 expression in ALL cells. The function of LINC00221 in ALL was determined by ki-67 immunofluorescence staining, EdU, TUNEL, JC-1, and caspase-3/8/9 activity assays. RNA pull down and Ago2-RNA immunoprecipitation (RIP) assays investigated the interaction between miR-152-3p and LINC00221 or ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 2 (ATP2A2). Our study revealed the low expression of LINC00221 in ALL cells. Subsequently, LINC00221 was verified to bind with miR-152-3p. Moreover, functional assays pointed out that LINC00221 overexpression posed anti-proliferation and pro-apoptosis effects in ALL cells, and these effects could be separately reversed by miR-152-3p up-regulation. Afterward, LINC00221 was revealed to regulate ATP2A2 expression via sponging miR-152-3p. Additionally, ATP2A2 was verified to involve in regulating LINC00221-mediated ALL cell proliferation and apoptosis. In conclusion, LINC00221 suppressed ALL cell proliferation and boosted ALL cell apoptosis via sponging miR-152-3p to up-regulate ATP2A2.

scholarly journals Oncorequisite role of an aldehyde dehydrogenase in the pathogenesis of T-cell acute lymphoblastic leukemia

Haematologica ◽  
2020 ◽  
pp. haematol.2019.245639
Author(s):  
Chujing Zhang ◽  
Stella Amanda ◽  
Cheng Wang ◽  
Tze King Tan ◽  
Muhammad Zulfaqar Ali ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Aldehyde Dehydrogenase ◽  
Lymphoblastic Leukemia ◽  
Cell Acute Lymphoblastic Leukemia

scholarly journals miR-141-3p and TRAF5 Network Contributes to the Progression of T-Cell Acute Lymphoblastic Leukemia

2019 ◽  
Vol 28 (1_suppl) ◽  
pp. 59S-65S ◽  
Author(s):  
Ruiqing Zhou ◽  
Wenjian Mo ◽  
Shunqing Wang ◽  
Wei Zhou ◽  
Xiaowei Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cell Apoptosis ◽  
Lymphoblastic Leukemia ◽  
Tumor Necrosis Factor Receptor ◽  
Underlying Mechanism ◽  
Vital Role ◽  
Cell Progression ◽  
Cell Acute Lymphoblastic Leukemia

Numerous lines of evidence have shown that microRNAs (miRNAs) play a vital role in regulating the progression in many types of cancers, including T cell acute lymphoblastic leukemia (T-ALL). In this study, the potential underlying mechanism and functional role of miR-141-3p in T-ALL cells were determined. We found that the expression level of miR-141-3p was significantly downregulated, while that of tumor necrosis factor receptor-associated factor 5 (TRAF5) was strongly upregulated in tissues from patients with T-ALL compared with healthy controls. Subsequently, upregulation of miR-141-3p significantly repressed T-ALL cell proliferation and promoted cell apoptosis. Conversely, downregulation of miR-141-3p significantly inhibited cell apoptosis and enhanced T-ALL cell proliferation. We also verified that TRAF5 was the direct target of miR-141-3p in T-ALL cells. Additionally, TRAF5 overexpression significantly repressed cell apoptosis and increased T-ALL cell proliferation. In summary, miR-141-3p regulates T-ALL cell progression by directly targeting TRAF5, and may serve as a potential therapeutic target for T-ALL.

L-arginine depletion by PEG-arginase I, a new potential therapy for acute lymphoblastic leukemia.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6580-6580
Author(s):  
Ofelia Crombet Ramos ◽  
Claudia Hernandez ◽  
Kevin Morrow ◽  
John T. Cole ◽  
Paulo Rodriguez
Keyword(s):  
Cell Proliferation ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
De Novo ◽  
Remission Rate ◽  
Lymphoblastic Leukemia ◽  
Arginase I

6580 Background: Advances in therapies have resulted in an overall complete remission rate of approximately 85% for childhood acute lymphoblastic leukemia (ALL). In contrast, the overall remission rate of adults with leukemia continues to be poor, only about 40% in cases of T cell-ALL (T-ALL). Therefore, it is imperative to generate new therapies that alone or in combination with other treatments could potentially increase the percentages of complete responders or be used to treat the refractory ALL population. Our published results show that a pegylated form of human arginase I (peg-Arg I) prevented T-ALL cell proliferation in vitro and in vivo through the induction of tumor cell apoptosis. Interestingly, the anti-leukemic effects induced by peg-Arg I did not affect the anti-tumor activity of normal T cells, suggesting an anti-tumor specific effect. Our hypothesis states that peg-Arg I has an anti-tumoral effect on B-ALL and T-ALL cells in vitro and that the sensitivity of ALL cells to peg-Arg I depends on their expression of argininosuccinate synthase (ASS) and their ability to produce L-arginine de novo from citrulline. Methods: Malignant T cell proliferation was tested using nonradioactive cell proliferation yellow tretrazolium salt kit. Apoptosis studies were based on the expression of annexin V. Western blot assays were conducted to determine enzymatic expression in different cell lines. Results: The results of our in vitro experiments showed that peg-Arg I had a pro-apoptotic and anti-proliferattive effect on B-ALL cells similar to the one previously seen on T-ALL cells. These effects can be overcome in cell lines able that express ASS and therefore to produce L-arginine de novo. Conclusions: Our results suggest the role of ASS in the ALL-apoptosis induced by peg-Arg-I. Our next steps include: _Understand why ASS-expressing ALL cells do not undergo apoptosis when cultured with peg-Arg-I_Determine the role of ASS in the anti-leukemic effect induced by peg-Arg-I in vivo. Completion of this research is expected to lead to a better understanding of how peg-Arg-I kills ALL cells and could provide the foundation for a novel therapy for ALL patients.

Expanding The TLX1-Regulome In T Cell Acute Lymphoblastic Leukemia Towards Long Non-Coding RNAs

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 813-813
Author(s):  
Kaat Durinck ◽  
Joni Van der Meulen ◽  
Maté Ongenaert ◽  
Pieter-Jan Volders ◽  
Annelynn Wallaert ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Expression Profiles ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Protein Coding ◽  
Chip Sequencing ◽  
Lncrna Expression ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Non Coding Rnas

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive cancer that results from the malignant transformation of T-cell precursors and affects children, adolescents and adults. In T-ALL, genetic lesions in several possible oncogenes and tumor suppressors have been shown to cooperatively contribute to leukemogenesis. The TLX1 (T-cell leukemia homeobox protein-1, HOX11) oncoprotein is aberrantly expressed in in 5-10% of pediatric patients and 30% of adult T-ALL patients due to chromosomal translocations. Although many downstream protein coding targets genes of TLX1 have been identified, the non-coding network downstream of TLX1 remains elusive. In this study we expand the TLX1 regulome towards long non-coding RNAs (lncRNAs). Hereto we measured the transcriptional response of all protein coding genes and 12,000 lncRNAs following TLX1 knock down in the ALL-SIL cell line using a custom designed mRNA/lncRNA expression platform (Agilent). In addition, similar mRNA-lncRNA expression profiles of 64 primary T-ALL patient samples were generated which included five TLX1+ cases. To establish the direct transcriptional TLX1 targets, we generated TLX1 ChIP-sequencing data from ALL-SIL leukemic cells. We confirm direct regulation of previously established protein coding gene targets and de novo TLX1 motif discovery also identified RUNX1 as an important mediator of the global TLX1 transcriptional network (Della Gatta et al., Nature Medicine, 2012). Complementary to these data, our analysis for the first time establishes the TLX1 driven lncRNAome in thymocyte derived leukemic cells. Remarkably, the majority of TLX1 controlled lncRNAs were upregulated suggesting that they may be implicated in the TLX1 driven repression of protein coding gene expression. Finally, pairwise mRNA-lncRNA correlation analysis allowed functional annotation of TLX1 targeted lncRNAs. In conclusion, we present the first landscaping of the genome-wide binding pattern of TLX1 and provide evidence for a previously unestablished role of lncRNAs in the TLX1 regulatory network. Disclosures: No relevant conflicts of interest to declare.

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