ADAMTS9-AS1 Constrains Breast Cancer Cell Invasion and Proliferation via Sequestering miR-301b-3p

Objective: For determination of how ADAMTS9-AS1/miR-301b-3p/TGFBR2/JAK STAT signaling axis modulates progression of breast cancer cells.Methods: Target lncRNA was determined by differential analysis of breast cancer expression data and survival analysis. Differentially expressed miRNAs and target mR...

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Autores principales: Junqing Chen, Ling Cheng, Weibin Zou, Rong Wang, Xiaojia Wang, Zhanhong Chen
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Lenguaje:EN
Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/daa16a7cd153466bb1cd0711e392107e
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spelling oai:doaj.org-article:daa16a7cd153466bb1cd0711e392107e2021-11-30T18:16:58ZADAMTS9-AS1 Constrains Breast Cancer Cell Invasion and Proliferation via Sequestering miR-301b-3p2296-634X10.3389/fcell.2021.719993https://doaj.org/article/daa16a7cd153466bb1cd0711e392107e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.719993/fullhttps://doaj.org/toc/2296-634XObjective: For determination of how ADAMTS9-AS1/miR-301b-3p/TGFBR2/JAK STAT signaling axis modulates progression of breast cancer cells.Methods: Target lncRNA was determined by differential analysis of breast cancer expression data and survival analysis. Differentially expressed miRNAs and target mRNAs that had binding sites with target lncRNA were predicted. GSEA software was used to carry out pathway enrichment analysis for mRNAs. Binding of the researched genes were tested with RNA binding protein immunoprecipitation (RIP). How miR-301b-3p bound TGFBR2 mRNA was tested by dual-luciferase method. Transwell, colony formation, EdU approaches were employed for verification of invasion and proliferation of breast cancer cells in each treatment group.Results: Markedly inactivated ADAMTS9-AS1 in breast cancer pertained to patient’s prognosis. MiR-301b-3p was capable of binding TGFBR2/ADAMTS9-AS1. However, overexpression of ADAMTS9-AS1 stimulated miR-301b-3p binding ADAMTS9-AS1 and repressed miR-301b-3p binding TGFBR2 mRNA. ADAMTS9-AS1 interference enhanced cancer proliferation and invasion, facilitated levels of KI67, PCNA, MMP-9 and MMP-2, and activated the JAK STAT signaling pathway. While silencing miR-301b-3p reversed the effect of ADAMTS9-AS1 interference. In addition, TGFBR2 interference or restraining JAK STAT signaling counteracted the effect of ADAMTS9-AS1.Conclusion: ADAMTS9-AS1 could sequester miR-301b-3p to inhibit progression of breast cancer via TGFBR2/JAK STAT pathway. This study supplies a rationale for incremental apprehension of ADAMTS9-AS1 in breast cancer progression.Junqing ChenJunqing ChenLing ChengWeibin ZouWeibin ZouRong WangRong WangXiaojia WangXiaojia WangZhanhong ChenZhanhong ChenFrontiers Media S.A.articleADAMTS9-AS1miR-301b-3pTGFBR2JAK STAT signaling pathwaybreast cancerBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution DOAJ
collection DOAJ
language EN
topic ADAMTS9-AS1
miR-301b-3p
TGFBR2
JAK STAT signaling pathway
breast cancer
Biology (General)
QH301-705.5
spellingShingle ADAMTS9-AS1
miR-301b-3p
TGFBR2
JAK STAT signaling pathway
breast cancer
Biology (General)
QH301-705.5
Junqing Chen
Junqing Chen
Ling Cheng
Weibin Zou
Weibin Zou
Rong Wang
Rong Wang
Xiaojia Wang
Xiaojia Wang
Zhanhong Chen
Zhanhong Chen
ADAMTS9-AS1 Constrains Breast Cancer Cell Invasion and Proliferation via Sequestering miR-301b-3p
description Objective: For determination of how ADAMTS9-AS1/miR-301b-3p/TGFBR2/JAK STAT signaling axis modulates progression of breast cancer cells.Methods: Target lncRNA was determined by differential analysis of breast cancer expression data and survival analysis. Differentially expressed miRNAs and target mRNAs that had binding sites with target lncRNA were predicted. GSEA software was used to carry out pathway enrichment analysis for mRNAs. Binding of the researched genes were tested with RNA binding protein immunoprecipitation (RIP). How miR-301b-3p bound TGFBR2 mRNA was tested by dual-luciferase method. Transwell, colony formation, EdU approaches were employed for verification of invasion and proliferation of breast cancer cells in each treatment group.Results: Markedly inactivated ADAMTS9-AS1 in breast cancer pertained to patient’s prognosis. MiR-301b-3p was capable of binding TGFBR2/ADAMTS9-AS1. However, overexpression of ADAMTS9-AS1 stimulated miR-301b-3p binding ADAMTS9-AS1 and repressed miR-301b-3p binding TGFBR2 mRNA. ADAMTS9-AS1 interference enhanced cancer proliferation and invasion, facilitated levels of KI67, PCNA, MMP-9 and MMP-2, and activated the JAK STAT signaling pathway. While silencing miR-301b-3p reversed the effect of ADAMTS9-AS1 interference. In addition, TGFBR2 interference or restraining JAK STAT signaling counteracted the effect of ADAMTS9-AS1.Conclusion: ADAMTS9-AS1 could sequester miR-301b-3p to inhibit progression of breast cancer via TGFBR2/JAK STAT pathway. This study supplies a rationale for incremental apprehension of ADAMTS9-AS1 in breast cancer progression.
format article
author Junqing Chen
Junqing Chen
Ling Cheng
Weibin Zou
Weibin Zou
Rong Wang
Rong Wang
Xiaojia Wang
Xiaojia Wang
Zhanhong Chen
Zhanhong Chen
author_facet Junqing Chen
Junqing Chen
Ling Cheng
Weibin Zou
Weibin Zou
Rong Wang
Rong Wang
Xiaojia Wang
Xiaojia Wang
Zhanhong Chen
Zhanhong Chen
author_sort Junqing Chen
title ADAMTS9-AS1 Constrains Breast Cancer Cell Invasion and Proliferation via Sequestering miR-301b-3p
title_short ADAMTS9-AS1 Constrains Breast Cancer Cell Invasion and Proliferation via Sequestering miR-301b-3p
title_full ADAMTS9-AS1 Constrains Breast Cancer Cell Invasion and Proliferation via Sequestering miR-301b-3p
title_fullStr ADAMTS9-AS1 Constrains Breast Cancer Cell Invasion and Proliferation via Sequestering miR-301b-3p
title_full_unstemmed ADAMTS9-AS1 Constrains Breast Cancer Cell Invasion and Proliferation via Sequestering miR-301b-3p
title_sort adamts9-as1 constrains breast cancer cell invasion and proliferation via sequestering mir-301b-3p
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/daa16a7cd153466bb1cd0711e392107e
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