Long non‑coding RNA linc00239 promotes malignant behaviors and chemoresistance against doxorubicin partially via activation of the PI3K/Akt/mTOR pathway in acute myeloid leukaemia cells

Yang, Yuting; Dai, Wenshu; Sun, Yingwei; Zhao, Ziyi

doi:10.3892/or.2019.6991

Cited by 22 publications

(32 citation statements)

References 32 publications

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“…Secondly, PTEN plays critical roles in regulating not only hematopoietic stem cell activity through a Niche-dependent mechanism, but also hematopoiesis and leukemogenesis [341][342][343]. Furthermore, TAL1, c-Jun, EZH2, TRIM22, ETV6/RUNX1, miR-7, -22, -26b, -103, -125b, -126, -139-5p, -181c, -193a, -628, and -3142, as well as LncRNA HULC, UCA1, linc00239 and LINC00265 control leukemogenesis, proliferation, apoptosis or chemoresistance via PI3K/AKT pathway [344][345][346][347][348][349][350][351][352][353][354][355][356][357][358][359][360][361][362][363]. Hereafter, PI3K/AKT pathway inhibition is regarded as a therapeutic approach [364,365] followed by the preclinical studies in leukemia cells [366,367] in spite of the upregulated expression of P2RY14 in acute leukemia cells resistant to PI3K/ mTOR inhibition [368].…”

Section: (Nct01002248; Nct01476137; Nct00881946) (Tables 2 and 3)mentioning

confidence: 99%

Role of PI3K/AKT pathway in cancer: the framework of malignant behavior

et al. 2020

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Given that the PI3K/AKT pathway has manifested its compelling influence on multiple cellular process, we further review the roles of hyperactivation of PI3K/AKT pathway in various human cancers. We state the abnormalities of PI3K/AKT pathway in different cancers, which are closely related with tumorigenesis, proliferation, growth, apoptosis, invasion, metastasis, epithelial-mesenchymal transition, stem-like phenotype, immune microenvironment and drug resistance of cancer cells. In addition, we investigated the current clinical trials of inhibitors against PI3K/AKT pathway in cancers and found that the clinical efficacy of these inhibitors as monotherapy has so far been limited despite of the promising preclinical activity, which means combinations of targeted therapy may achieve better efficacies in cancers. In short, we hope to feature PI3K/ AKT pathway in cancers to the clinic and bring the new promising to patients for targeted therapies.

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Section: (Nct01002248; Nct01476137; Nct00881946) (Tables 2 and 3)mentioning

confidence: 99%

Role of PI3K/AKT pathway in cancer: the framework of malignant behavior

et al. 2020

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“…Linc00239 regulates chemoresistance to doxorubicin and exerts a protective effect against apoptotic cell death, promotes cell viability, cell cycle distribution, colony formation and migration. This lncRNA leads to mTOR/AKT activation (90). The overactivation of SOX61 in AML leads to increased cell proliferation and inhibited cell apoptosis in KG-1 cells and THP-1 cell (97).…”

Section: Current Research On Long Non-coding Rnas In Myeloid Malignanmentioning

confidence: 99%

“…Linc00239 is another lncRNA whose increased expression is related to a higher resistance to doxorubicin, as shown by the KG-1 and HL-60 AML cell lines. However, it is involved in the intrinsic resistance to chemotherapy and its expression in acquired chemoresistance was not evaluated (90). HOXA-AS2 is overexpressed in the bone marrow of patients who acquired adriamycin resistance.…”

Section: Long Non-coding Rnas In Myeloid Malignancies—analysis Of Tcgmentioning

confidence: 99%

“…The presence of linc00239 increases chemoresistance to doxorubicin in AML cells partially by preventing doxorubicin-induced apoptotic cell death and is linked to the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. Thus, the inhibition of PI3K/Akt/mTOR using 1 μM NVP-BEZ235 (BEZ) abolished the inhibitory effect of linc00239 on chemosensitivity and the preventative effect on doxorubicin-induced cell death (90). Their use could be implemented in risk stratification and prognosis in the clinic.…”

Section: Long Non-coding Rnas In Myeloid Malignancies—analysis Of Prementioning

confidence: 99%

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Long Non-coding RNAs in Myeloid Malignancies

et al. 2019

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Acute myeloid leukemia (AML) represents 80% of adult leukemias and 15–20% of childhood leukemias. AML are characterized by the presence of 20% blasts or more in the bone marrow, or defining cytogenetic abnormalities. Laboratory diagnoses of myelodysplastic syndromes (MDS) depend on morphological changes based on dysplasia in peripheral blood and bone marrow, including peripheral blood smears, bone marrow aspirate smears, and bone marrow biopsies. As leukemic cells are not functional, the patient develops anemia, neutropenia, and thrombocytopenia, leading to fatigue, recurrent infections, and hemorrhage. The genetic background and associated mutations in AML blasts determine the clinical course of the disease. Over the last decade, non-coding RNAs transcripts that do not codify for proteins but play a role in regulation of functions have been shown to have multiple applications in the diagnosis, prognosis and therapeutic approach of various types of cancers, including myeloid malignancies. After a comprehensive review of current literature, we found reports of multiple long non-coding RNAs (lncRNAs) that can differentiate between AML types and how their exogenous modulation can dramatically change the behavior of AML cells. These lncRNAs include: H19, LINC00877, RP11-84C10, CRINDE, RP11848P1.3, ZNF667-AS1, AC111000.4-202, SFMBT2, LINC02082-201, MEG3, AC009495.2, PVT1, HOTTIP, SNHG5, and CCAT1. In addition, by performing an analysis on available AML data in The Cancer Genome Atlas (TCGA), we found 10 lncRNAs with significantly differential expression between patients in favorable, intermediate/normal, or poor cytogenetic risk categories. These are: DANCR, PRDM16-DT, SNHG6, OIP5-AS1, SNHG16, JPX, FTX, KCNQ1OT1, TP73-AS1, and GAS5. The identification of a molecular signature based on lncRNAs has the potential for have deep clinical significance, as it could potentially help better define the evolution from low-grade MDS to high-grade MDS to AML, changing the course of therapy. This would allow clinicians to provide a more personalized, patient-tailored therapeutic approach, moving from transfusion-based therapy, as is the case for low-grade MDS, to the introduction of azacytidine-based chemotherapy or allogeneic stem cell transplantation, which is the current treatment for high-grade MDS.

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“…23 LncRNA linc00239 was found to be up-regulated in AML patients and two AML cell lines, and overexpressed linc00239 promoted proliferation, colony formation and migration ability of AML cells. 24 Long non-coding RNA zinc finger antisense 1 (ZFAS1) has been reported to be upregulated in the bone marrow of acute leukemia patients and AML cell lines. And researchers validated that the silencing of ZFAS1 blocked the progression of AML by regulating miR-150/ Sp1 and miR-150/Myb pathways.…”

Section: Dovepressmentioning

confidence: 99%

<p>LncRNA TUG1 Regulates Cell Viability and Death by Regulating miR-193a-5p/Rab10 Axis in Acute Myeloid Leukemia</p>

Li¹,

Wang²

2020

OTT

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Background: Acute myeloid leukemia (AML) is a serious threat to human health. Long non-coding RNA (lncRNA) Taurine-Upregulated Gene1 (TUG1) has been reported to participate in the development and progression of several cancers, including AML. Herein, we aimed to investigate the pathognomonic role of TUG1 in AML cells and its potential mechanistic pathway. Methods: Quantitative real-time PCR (qRT-PCR) assay was applied to detect the expression levels of lncRNA TUG1, miR-193a-5p and Rab10 in AML bone marrow and cell lines. The CCK-8 assay was conducted to assess the cell viability of AML HL-60 and NB4 cells and cell apoptotic assay was performed to assess the cell death. Dual-luciferase reporter assay was carried out to clarify the relationships among TUG1, miR-193a-5p and Rab10. Also, the protein level of Rab10 was examined by Western blot assay. Results: LncRNA TUG1 was up-regulated in AML bone marrow and cells. Functional analysis showed that the silencing of TUG1 suppressed cell viability, while promoted cell death in AML HL-60 and NB4 cells. TUG1 targeted miR-193a-5p and negatively regulated miR-193a-5p expression. Overexpressed miR-193a-5p resulted in the decrease of cell viability and the increase in the cell death in AML cells. Restoration experiments proved that TUG1 regulated the cell viability and death of AML cells through regulating the miR-193a-5p/Rab10 axis. Rab10 was a direct target of miR-193a-5p and was inversely regulated by miR-193a-5p. TUG1 regulated the cell viability and death of AML cells through upregulating Rab10. Conclusion: Silencing of lncRNA TUG1 induces a cytotoxic effect on AML cell lines through sponging miR-193a-5p and the suppression of Rab10.

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Long non‑coding RNA linc00239 promotes malignant behaviors and chemoresistance against doxorubicin partially via activation of the PI3K/Akt/mTOR pathway in acute myeloid leukaemia cells

Cited by 22 publications

References 32 publications

Role of PI3K/AKT pathway in cancer: the framework of malignant behavior

Role of PI3K/AKT pathway in cancer: the framework of malignant behavior

Long Non-coding RNAs in Myeloid Malignancies

<p>LncRNA TUG1 Regulates Cell Viability and Death by Regulating miR-193a-5p/Rab10 Axis in Acute Myeloid Leukemia</p>

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