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Knockdown of LncRNA DLEU2 Inhibits Cervical Cancer Progression via Targeting miR-128-3p

OBJECTIVE: Cervical cancer is one of the most common female malignancies worldwide and represents a major global health challenge. The fast growth of tumor and high rates of metastasis still lead to a poor prognosis of cervical cancer patients. It is urgent to clarify the mechanism and identify pred...

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Autores principales: Wang, Bofei, Hang, Jing, Li, Weiling, Yuan, Wanqiong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553767/
https://www.ncbi.nlm.nih.gov/pubmed/33116599
http://dx.doi.org/10.2147/OTT.S272292
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author Wang, Bofei
Hang, Jing
Li, Weiling
Yuan, Wanqiong
author_facet Wang, Bofei
Hang, Jing
Li, Weiling
Yuan, Wanqiong
author_sort Wang, Bofei
collection PubMed
description OBJECTIVE: Cervical cancer is one of the most common female malignancies worldwide and represents a major global health challenge. The fast growth of tumor and high rates of metastasis still lead to a poor prognosis of cervical cancer patients. It is urgent to clarify the mechanism and identify predictive biomarkers for the treatment of cervical cancer. Long non-coding RNAs (LncRNAs) have been identified in cervical cancer and are related to malignant phenotypes of cervical cancer cells. However, the roles and mechanism of LncRNA deleted in lymphocytic leukemia (DLEU2) in the tumorigenesis and progression of cervical cancer remain unknown. MATERIALS AND METHODS: qPCR was performed to analyze the expression of DLEU2, Cyclin D1, CDK4, Bax, Bcl2 and mi-128-3p. Western blot was performed to detect the cell cycle hallmarks expression. CCK8 was used to examine cell proliferation. Cellular apoptosis was analyzed by Hoechst 33,258 staining and AV/PI staining with flow cytometry. Cell cycle was analyzed by flow cytometry. The xenograft model in nude mice was used to elucidate the function of DLEU2 in vivo. Bioinformatics analysis and luciferase reporter assay were proceeded to clarify whether miR-128-3p directly binds with lncRNA DLEU2. Pull‑down assay and RNA-binding protein immunoprecipitation assay were used for exploring the relationship between DLEU2 and miR-128-3p. RESULTS: We demonstrated that DLEU2 was upregulated in cervical cancer tumor tissues. Downregulation of DLEU2 inhibited cell proliferation, induced apoptosis and cell cycle arrest at G2/M phase of cervical cancer cells in vitro, and suppressed tumor growth in vivo. Further, LncRNA DLEU2 is one of the targets of miR-128-3p. miR-128-3p inhibitor abrogated the cell proliferation suppressed by knockdown of DLEU2, apoptosis induced by knockdown of DLEU2 and reversed the expression of cell cycle hallmarks regulated by knockdown of DLEU2. CONCLUSION: Taken together, these results suggested knockdown of DLEU2 inhibited cervical cancer progression via targeting miR-128-3p.
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spelling pubmed-75537672020-10-27 Knockdown of LncRNA DLEU2 Inhibits Cervical Cancer Progression via Targeting miR-128-3p Wang, Bofei Hang, Jing Li, Weiling Yuan, Wanqiong Onco Targets Ther Original Research OBJECTIVE: Cervical cancer is one of the most common female malignancies worldwide and represents a major global health challenge. The fast growth of tumor and high rates of metastasis still lead to a poor prognosis of cervical cancer patients. It is urgent to clarify the mechanism and identify predictive biomarkers for the treatment of cervical cancer. Long non-coding RNAs (LncRNAs) have been identified in cervical cancer and are related to malignant phenotypes of cervical cancer cells. However, the roles and mechanism of LncRNA deleted in lymphocytic leukemia (DLEU2) in the tumorigenesis and progression of cervical cancer remain unknown. MATERIALS AND METHODS: qPCR was performed to analyze the expression of DLEU2, Cyclin D1, CDK4, Bax, Bcl2 and mi-128-3p. Western blot was performed to detect the cell cycle hallmarks expression. CCK8 was used to examine cell proliferation. Cellular apoptosis was analyzed by Hoechst 33,258 staining and AV/PI staining with flow cytometry. Cell cycle was analyzed by flow cytometry. The xenograft model in nude mice was used to elucidate the function of DLEU2 in vivo. Bioinformatics analysis and luciferase reporter assay were proceeded to clarify whether miR-128-3p directly binds with lncRNA DLEU2. Pull‑down assay and RNA-binding protein immunoprecipitation assay were used for exploring the relationship between DLEU2 and miR-128-3p. RESULTS: We demonstrated that DLEU2 was upregulated in cervical cancer tumor tissues. Downregulation of DLEU2 inhibited cell proliferation, induced apoptosis and cell cycle arrest at G2/M phase of cervical cancer cells in vitro, and suppressed tumor growth in vivo. Further, LncRNA DLEU2 is one of the targets of miR-128-3p. miR-128-3p inhibitor abrogated the cell proliferation suppressed by knockdown of DLEU2, apoptosis induced by knockdown of DLEU2 and reversed the expression of cell cycle hallmarks regulated by knockdown of DLEU2. CONCLUSION: Taken together, these results suggested knockdown of DLEU2 inhibited cervical cancer progression via targeting miR-128-3p. Dove 2020-10-09 /pmc/articles/PMC7553767/ /pubmed/33116599 http://dx.doi.org/10.2147/OTT.S272292 Text en © 2020 Wang et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Wang, Bofei
Hang, Jing
Li, Weiling
Yuan, Wanqiong
Knockdown of LncRNA DLEU2 Inhibits Cervical Cancer Progression via Targeting miR-128-3p
title Knockdown of LncRNA DLEU2 Inhibits Cervical Cancer Progression via Targeting miR-128-3p
title_full Knockdown of LncRNA DLEU2 Inhibits Cervical Cancer Progression via Targeting miR-128-3p
title_fullStr Knockdown of LncRNA DLEU2 Inhibits Cervical Cancer Progression via Targeting miR-128-3p
title_full_unstemmed Knockdown of LncRNA DLEU2 Inhibits Cervical Cancer Progression via Targeting miR-128-3p
title_short Knockdown of LncRNA DLEU2 Inhibits Cervical Cancer Progression via Targeting miR-128-3p
title_sort knockdown of lncrna dleu2 inhibits cervical cancer progression via targeting mir-128-3p
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553767/
https://www.ncbi.nlm.nih.gov/pubmed/33116599
http://dx.doi.org/10.2147/OTT.S272292
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