Long non-coding RNA CRNDE exacerbates NPC advancement mediated by the miR-545-5p/CCND2 axis

Abstract Background Previous studies indicated CRNDE to have a pivotal part within tumorigenesis. Notwithstanding, precise details on CRNDE activities within NPC are still uncertain. The investigation described in this article served to focus in greater depth on the mechanistics regarding CRNDE, tog...

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Autores principales: Sichen Ge, Chengyi Jiang, Min Li, Zhongqiang Cheng, Xiaojia Feng
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Publicado: BMC 2021
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NPC
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spelling oai:doaj.org-article:552a26aae0d14c97b13baf0193917a452021-12-05T12:23:38ZLong non-coding RNA CRNDE exacerbates NPC advancement mediated by the miR-545-5p/CCND2 axis10.1186/s12935-021-02348-21475-2867https://doaj.org/article/552a26aae0d14c97b13baf0193917a452021-12-01T00:00:00Zhttps://doi.org/10.1186/s12935-021-02348-2https://doaj.org/toc/1475-2867Abstract Background Previous studies indicated CRNDE to have a pivotal part within tumorigenesis. Notwithstanding, precise details on CRNDE activities within NPC are still uncertain. The investigation described in this article served to focus in greater depth on the mechanistics regarding CRNDE, together with all associated regulatory networks, on nasopharyngeal carcinoma (NPC) and its treatment possibilities. Methods Quantitative real-time polymerase chain reaction (RT-qPCR) analyzed CRNDE, miR-545-5p and CCND2 expression within NPCs and representative cell lineages. CCK-8 cell counting-, EdU-, wound-healing-/transwell-assays analyzed cellular proliferation, migrative, together with invasive properties. Apoptosis/cell cycle progression were scrutinized through flow cytometry. Dual-luciferase reporter assays validated CRNDE/miR-545-5p/CCND2 interplay. Proteomic expression of apoptosis-related protein, EMT-related protein and CCND2 protein were evaluated through Western blotting. In addition, Ki67 expression was evaluated through immunohistochemical staining. The effect of CRNDE in vivo was assessed by nude murine xenograft model studies. Results This study demonstrated up-regulated expression of CRNDE and CCND2 within NPC tissues/cell lines. Meanwhile, miR-545-5p was down-regulated. CRNDE knock-down or miR-545-5p over-expression drastically reduced NPC proliferative, migrative and invasive properties, promoted apoptosis/altered cell cycle, and inhibited CCND2 expression. However, miR-545-5p down-regulation had opposing effects. All inhibiting functions generated by CRNDE down-regulation upon NPC progression could be counterbalanced or synergistically exacerbated, depending on miR-545-5p down-regulation or up-regulation, respectively. Multiple-level investigations revealed CRNDE to serve as a sponge for miR-545-5p, and can target CCND2 within NPCs. Conclusions CRNDE increases CCND2 expression by competitive binding with miR-545-5p, thus accelerating the development of NPC. This provides potential therapeutic targets and prognostic markers against NPC.Sichen GeChengyi JiangMin LiZhongqiang ChengXiaojia FengBMCarticleLncRNA CRNDENPCmiR-545-5pCCND2Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282CytologyQH573-671ENCancer Cell International, Vol 21, Iss 1, Pp 1-14 (2021)
institution DOAJ
collection DOAJ
language EN
topic LncRNA CRNDE
NPC
miR-545-5p
CCND2
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Cytology
QH573-671
spellingShingle LncRNA CRNDE
NPC
miR-545-5p
CCND2
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Cytology
QH573-671
Sichen Ge
Chengyi Jiang
Min Li
Zhongqiang Cheng
Xiaojia Feng
Long non-coding RNA CRNDE exacerbates NPC advancement mediated by the miR-545-5p/CCND2 axis
description Abstract Background Previous studies indicated CRNDE to have a pivotal part within tumorigenesis. Notwithstanding, precise details on CRNDE activities within NPC are still uncertain. The investigation described in this article served to focus in greater depth on the mechanistics regarding CRNDE, together with all associated regulatory networks, on nasopharyngeal carcinoma (NPC) and its treatment possibilities. Methods Quantitative real-time polymerase chain reaction (RT-qPCR) analyzed CRNDE, miR-545-5p and CCND2 expression within NPCs and representative cell lineages. CCK-8 cell counting-, EdU-, wound-healing-/transwell-assays analyzed cellular proliferation, migrative, together with invasive properties. Apoptosis/cell cycle progression were scrutinized through flow cytometry. Dual-luciferase reporter assays validated CRNDE/miR-545-5p/CCND2 interplay. Proteomic expression of apoptosis-related protein, EMT-related protein and CCND2 protein were evaluated through Western blotting. In addition, Ki67 expression was evaluated through immunohistochemical staining. The effect of CRNDE in vivo was assessed by nude murine xenograft model studies. Results This study demonstrated up-regulated expression of CRNDE and CCND2 within NPC tissues/cell lines. Meanwhile, miR-545-5p was down-regulated. CRNDE knock-down or miR-545-5p over-expression drastically reduced NPC proliferative, migrative and invasive properties, promoted apoptosis/altered cell cycle, and inhibited CCND2 expression. However, miR-545-5p down-regulation had opposing effects. All inhibiting functions generated by CRNDE down-regulation upon NPC progression could be counterbalanced or synergistically exacerbated, depending on miR-545-5p down-regulation or up-regulation, respectively. Multiple-level investigations revealed CRNDE to serve as a sponge for miR-545-5p, and can target CCND2 within NPCs. Conclusions CRNDE increases CCND2 expression by competitive binding with miR-545-5p, thus accelerating the development of NPC. This provides potential therapeutic targets and prognostic markers against NPC.
format article
author Sichen Ge
Chengyi Jiang
Min Li
Zhongqiang Cheng
Xiaojia Feng
author_facet Sichen Ge
Chengyi Jiang
Min Li
Zhongqiang Cheng
Xiaojia Feng
author_sort Sichen Ge
title Long non-coding RNA CRNDE exacerbates NPC advancement mediated by the miR-545-5p/CCND2 axis
title_short Long non-coding RNA CRNDE exacerbates NPC advancement mediated by the miR-545-5p/CCND2 axis
title_full Long non-coding RNA CRNDE exacerbates NPC advancement mediated by the miR-545-5p/CCND2 axis
title_fullStr Long non-coding RNA CRNDE exacerbates NPC advancement mediated by the miR-545-5p/CCND2 axis
title_full_unstemmed Long non-coding RNA CRNDE exacerbates NPC advancement mediated by the miR-545-5p/CCND2 axis
title_sort long non-coding rna crnde exacerbates npc advancement mediated by the mir-545-5p/ccnd2 axis
publisher BMC
publishDate 2021
url https://doaj.org/article/552a26aae0d14c97b13baf0193917a45
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AT minli longnoncodingrnacrndeexacerbatesnpcadvancementmediatedbythemir5455pccnd2axis
AT zhongqiangcheng longnoncodingrnacrndeexacerbatesnpcadvancementmediatedbythemir5455pccnd2axis
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