NAALADL2-AS2 functions as a competing endogenous RNA to regulate apoptosis and drug resistance in DLBCL

To explore role of NAALADL2-AS2 as ceRNA in DLBCL. Fluorescence in situ hybridization was used to determine location of NAALADL2-AS2 in cells and to verify its expression in DLBCL tissues. The miRNAs interacting with NAALADL2-AS2 and related regulatory genes were identified by small interfering RNA...

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Main Authors: Xiaoli Xu, Juan Liu, Cheng Fang, Xu Deng, Danxia Zhu, Jingting Jiang, Changping Wu
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Cancer Biology & Therapy
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Online Access:https://www.tandfonline.com/doi/10.1080/15384047.2024.2432690
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author Xiaoli Xu
Juan Liu
Cheng Fang
Xu Deng
Danxia Zhu
Jingting Jiang
Changping Wu
author_facet Xiaoli Xu
Juan Liu
Cheng Fang
Xu Deng
Danxia Zhu
Jingting Jiang
Changping Wu
author_sort Xiaoli Xu
collection DOAJ
description To explore role of NAALADL2-AS2 as ceRNA in DLBCL. Fluorescence in situ hybridization was used to determine location of NAALADL2-AS2 in cells and to verify its expression in DLBCL tissues. The miRNAs interacting with NAALADL2-AS2 and related regulatory genes were identified by small interfering RNA (siRNA) assay, luciferase reporter assay, fluorescent quantitative polymerase chain reaction, western blotting. DLBCL cells transfected with NAALADL2-AS2 siRNA or control siRNA were treated with doxorubicin, rituximab at different concentrations alone or in combination. The growth curves, drug sensitivity changes of cells before and after transfection were detected by MTT assay, ATP-TCA drug sensitivity test. Cell proliferation was detected by BrdU cell proliferation assay, and apoptosis was detected by Annexin V-fluorescein isothiocyanate/propidium iodide staining. The effects and mechanisms of NAALADL2-AS2 on proliferation, apoptosis, drug resistance of DLBCL cells were studied at cellular level. We confirmed expression of NAALADL2-AS2 in both cytoplasm and nuclei of DLBCL cells. Additionally, we observed elevated levels of NAALADL2-AS2 in DLBCL tissues. We discovered that NAALADL2-AS2 functions as ceRNA to inhibit expression of miR-34a, miR-125a, whereas overexpression of NAALADL2-AS2 indirectly upregulates expression of BCL-2. Interfering with NAALADL2-AS2 promoted apoptosis in DLBCL cells, resulting in approximately a 40% increase in sensitivity to doxorubicin and rituximab. In vivo experiments further confirmed that targeting NAALADL2-AS2 effectively suppressed tumor growth, leading to upregulation of miR-34a and miR-125a, downregulation of BCL-2, and enhanced apoptosis in DLBCL cells, which significantly improved their sensitivity to doxorubicin and rituximab by approximately 50%. These results indicate that NAALADL2-AS2/miR-34a, miR-125a/BCL-2 networks hold promise as therapeutic targets for treatment of DLBCL.
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spelling doaj-art-5e15e97e17f14e6f83924508becd3f5a2024-12-13T06:53:24ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762024-12-0125110.1080/15384047.2024.2432690NAALADL2-AS2 functions as a competing endogenous RNA to regulate apoptosis and drug resistance in DLBCLXiaoli Xu0Juan Liu1Cheng Fang2Xu Deng3Danxia Zhu4Jingting Jiang5Changping Wu6Department of Integrated Chinese and Western Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, ChinaDepartment of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, ChinaDepartment of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, ChinaDepartment of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, ChinaDepartment of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, ChinaDepartment of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, ChinaDepartment of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, ChinaTo explore role of NAALADL2-AS2 as ceRNA in DLBCL. Fluorescence in situ hybridization was used to determine location of NAALADL2-AS2 in cells and to verify its expression in DLBCL tissues. The miRNAs interacting with NAALADL2-AS2 and related regulatory genes were identified by small interfering RNA (siRNA) assay, luciferase reporter assay, fluorescent quantitative polymerase chain reaction, western blotting. DLBCL cells transfected with NAALADL2-AS2 siRNA or control siRNA were treated with doxorubicin, rituximab at different concentrations alone or in combination. The growth curves, drug sensitivity changes of cells before and after transfection were detected by MTT assay, ATP-TCA drug sensitivity test. Cell proliferation was detected by BrdU cell proliferation assay, and apoptosis was detected by Annexin V-fluorescein isothiocyanate/propidium iodide staining. The effects and mechanisms of NAALADL2-AS2 on proliferation, apoptosis, drug resistance of DLBCL cells were studied at cellular level. We confirmed expression of NAALADL2-AS2 in both cytoplasm and nuclei of DLBCL cells. Additionally, we observed elevated levels of NAALADL2-AS2 in DLBCL tissues. We discovered that NAALADL2-AS2 functions as ceRNA to inhibit expression of miR-34a, miR-125a, whereas overexpression of NAALADL2-AS2 indirectly upregulates expression of BCL-2. Interfering with NAALADL2-AS2 promoted apoptosis in DLBCL cells, resulting in approximately a 40% increase in sensitivity to doxorubicin and rituximab. In vivo experiments further confirmed that targeting NAALADL2-AS2 effectively suppressed tumor growth, leading to upregulation of miR-34a and miR-125a, downregulation of BCL-2, and enhanced apoptosis in DLBCL cells, which significantly improved their sensitivity to doxorubicin and rituximab by approximately 50%. These results indicate that NAALADL2-AS2/miR-34a, miR-125a/BCL-2 networks hold promise as therapeutic targets for treatment of DLBCL.https://www.tandfonline.com/doi/10.1080/15384047.2024.2432690Diffuse large B-cell lymphomaNAALADL2-AS2competitive endogenous RNAapoptosisdrug resistance
spellingShingle Xiaoli Xu
Juan Liu
Cheng Fang
Xu Deng
Danxia Zhu
Jingting Jiang
Changping Wu
NAALADL2-AS2 functions as a competing endogenous RNA to regulate apoptosis and drug resistance in DLBCL
Cancer Biology & Therapy
Diffuse large B-cell lymphoma
NAALADL2-AS2
competitive endogenous RNA
apoptosis
drug resistance
title NAALADL2-AS2 functions as a competing endogenous RNA to regulate apoptosis and drug resistance in DLBCL
title_full NAALADL2-AS2 functions as a competing endogenous RNA to regulate apoptosis and drug resistance in DLBCL
title_fullStr NAALADL2-AS2 functions as a competing endogenous RNA to regulate apoptosis and drug resistance in DLBCL
title_full_unstemmed NAALADL2-AS2 functions as a competing endogenous RNA to regulate apoptosis and drug resistance in DLBCL
title_short NAALADL2-AS2 functions as a competing endogenous RNA to regulate apoptosis and drug resistance in DLBCL
title_sort naaladl2 as2 functions as a competing endogenous rna to regulate apoptosis and drug resistance in dlbcl
topic Diffuse large B-cell lymphoma
NAALADL2-AS2
competitive endogenous RNA
apoptosis
drug resistance
url https://www.tandfonline.com/doi/10.1080/15384047.2024.2432690
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