Long Non-coding RNA BTG3-7:1 and JUND Co-regulate C21ORF91 to Promote Triple-Negative Breast Cancer Progress
BackgroundTriple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with poor prognosis. Recently, massive data reveal that long non-coding RNAs (lncRNAs) play important roles in cancer progress. Recently, although the role of lncRNAs in breast cancer has been well documented,...
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Frontiers Media S.A.
2021-01-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2020.605623/full |
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| author | Zheng Dan He Xiujing Luo Ting Zhong Xiaorong Zheng Hong Yang Jiqiao Li Yanchu Jing Jing |
| author_facet | Zheng Dan He Xiujing Luo Ting Zhong Xiaorong Zheng Hong Yang Jiqiao Li Yanchu Jing Jing |
| author_sort | Zheng Dan |
| collection | DOAJ |
| description | BackgroundTriple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with poor prognosis. Recently, massive data reveal that long non-coding RNAs (lncRNAs) play important roles in cancer progress. Recently, although the role of lncRNAs in breast cancer has been well documented, few focused on TNBC. In this study, we aimed to systematically identify functional lncRNAs and to explore its molecular mechanism on TNBC progress.MethodsThe recurrence of lncRNAs and their target genes were validated with TNBC biopsies and cell lines. Total one hundred and thirteen TNBC biopsies, including nineteen patient-matched samples, were collected. The profile of TNBC-related lncRNAs and their target genes were characterized by RNA sequencing (RNA-seq) and bioinformatic analysis. Tumor specific lncRNAs, which also showed biological function correlated with TNBC, were identified as potential candidates; and the target genes, which regulated by the identified lncRNAs, were predicted by the analysis of expression correlation and chromosome colocalization. Cross bioinformatic validation was performed with TNBC independent datasets from the cancer genome atlas (TCGA). The biological functions and molecular mechanism were investigated in TNBC model cell lines by cell colony forming assay, flow cytometry assay, western-blot, RNA Fluorescence in situ Hybridization assay (RNA FISH) and chromatin immunoprecipitation-qPCR (ChIP-qPCR).ResultsAbundant Lnc-BTG3-7:1, which targets gene C21ORF91, was specifically observed in TNBC biopsies and cell lines. Knockdown of Lnc-BTG3-7:1 or C21ORF91 strongly inhibited cell proliferation, promoted cell apoptosis and cell cycle G1-arrested. Meanwhile, investigation of molecular mechanism indicated that Lnc-BTG3-7:1, cooperated with transcription factor JUND, cis-regulated the transcription of C21ORF91 gene, and down-regulation of Lnc-BTG3-7:1/C21ORF91 suppressed GRB2-RAS-RAF-MEK-ERK and GRB2-PI3K-AKT-GSK3β-β-catenin pathways.ConclusionsIn this study, we identified a TNBC specific lncRNA Lnc-BTG3-7:1, which sustained tumor progress. Up-regulation of Lnc-BTG3-7:1 promoted the transcription of oncogene C21ORF91 and activated PI3K-AKT-GSK3β-β-catenin and MAPK pathways. Taken together, our results not only identified a biomarker for diagnosis but also provided a potential therapeutic target against TNBC. |
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| spelling | doaj.art-2b14ac8c14e942d889c3a77cf16f55f02022-12-21T19:51:33ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2021-01-01710.3389/fmolb.2020.605623605623Long Non-coding RNA BTG3-7:1 and JUND Co-regulate C21ORF91 to Promote Triple-Negative Breast Cancer ProgressZheng Dan0He Xiujing1Luo Ting2Zhong Xiaorong3Zheng Hong4Yang Jiqiao5Li Yanchu6Jing Jing7Laboratory of Tumor Targeted and Immune Therapy, Clinical Research Center for Breast, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Tumor Targeted and Immune Therapy, Clinical Research Center for Breast, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Head and Neck Oncology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Head and Neck Oncology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Head and Neck Oncology, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Tumor Targeted and Immune Therapy, Clinical Research Center for Breast, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Tumor Targeted and Immune Therapy, Clinical Research Center for Breast, West China Hospital, Sichuan University, Chengdu, ChinaLaboratory of Tumor Targeted and Immune Therapy, Clinical Research Center for Breast, West China Hospital, Sichuan University, Chengdu, ChinaBackgroundTriple-negative breast cancer (TNBC) is a type of highly invasive breast cancer with poor prognosis. Recently, massive data reveal that long non-coding RNAs (lncRNAs) play important roles in cancer progress. Recently, although the role of lncRNAs in breast cancer has been well documented, few focused on TNBC. In this study, we aimed to systematically identify functional lncRNAs and to explore its molecular mechanism on TNBC progress.MethodsThe recurrence of lncRNAs and their target genes were validated with TNBC biopsies and cell lines. Total one hundred and thirteen TNBC biopsies, including nineteen patient-matched samples, were collected. The profile of TNBC-related lncRNAs and their target genes were characterized by RNA sequencing (RNA-seq) and bioinformatic analysis. Tumor specific lncRNAs, which also showed biological function correlated with TNBC, were identified as potential candidates; and the target genes, which regulated by the identified lncRNAs, were predicted by the analysis of expression correlation and chromosome colocalization. Cross bioinformatic validation was performed with TNBC independent datasets from the cancer genome atlas (TCGA). The biological functions and molecular mechanism were investigated in TNBC model cell lines by cell colony forming assay, flow cytometry assay, western-blot, RNA Fluorescence in situ Hybridization assay (RNA FISH) and chromatin immunoprecipitation-qPCR (ChIP-qPCR).ResultsAbundant Lnc-BTG3-7:1, which targets gene C21ORF91, was specifically observed in TNBC biopsies and cell lines. Knockdown of Lnc-BTG3-7:1 or C21ORF91 strongly inhibited cell proliferation, promoted cell apoptosis and cell cycle G1-arrested. Meanwhile, investigation of molecular mechanism indicated that Lnc-BTG3-7:1, cooperated with transcription factor JUND, cis-regulated the transcription of C21ORF91 gene, and down-regulation of Lnc-BTG3-7:1/C21ORF91 suppressed GRB2-RAS-RAF-MEK-ERK and GRB2-PI3K-AKT-GSK3β-β-catenin pathways.ConclusionsIn this study, we identified a TNBC specific lncRNA Lnc-BTG3-7:1, which sustained tumor progress. Up-regulation of Lnc-BTG3-7:1 promoted the transcription of oncogene C21ORF91 and activated PI3K-AKT-GSK3β-β-catenin and MAPK pathways. Taken together, our results not only identified a biomarker for diagnosis but also provided a potential therapeutic target against TNBC.https://www.frontiersin.org/articles/10.3389/fmolb.2020.605623/fullTriple-negative breast cancerLnc-BTG3-7:1C21ORF91 geneGRB2-RAS-RAF-MEK-ERK pathwayGRB2-PI3K-AKT-GSK3β-β-catenin |
| spellingShingle | Zheng Dan He Xiujing Luo Ting Zhong Xiaorong Zheng Hong Yang Jiqiao Li Yanchu Jing Jing Long Non-coding RNA BTG3-7:1 and JUND Co-regulate C21ORF91 to Promote Triple-Negative Breast Cancer Progress Frontiers in Molecular Biosciences Triple-negative breast cancer Lnc-BTG3-7:1 C21ORF91 gene GRB2-RAS-RAF-MEK-ERK pathway GRB2-PI3K-AKT-GSK3β-β-catenin |
| title | Long Non-coding RNA BTG3-7:1 and JUND Co-regulate C21ORF91 to Promote Triple-Negative Breast Cancer Progress |
| title_full | Long Non-coding RNA BTG3-7:1 and JUND Co-regulate C21ORF91 to Promote Triple-Negative Breast Cancer Progress |
| title_fullStr | Long Non-coding RNA BTG3-7:1 and JUND Co-regulate C21ORF91 to Promote Triple-Negative Breast Cancer Progress |
| title_full_unstemmed | Long Non-coding RNA BTG3-7:1 and JUND Co-regulate C21ORF91 to Promote Triple-Negative Breast Cancer Progress |
| title_short | Long Non-coding RNA BTG3-7:1 and JUND Co-regulate C21ORF91 to Promote Triple-Negative Breast Cancer Progress |
| title_sort | long non coding rna btg3 7 1 and jund co regulate c21orf91 to promote triple negative breast cancer progress |
| topic | Triple-negative breast cancer Lnc-BTG3-7:1 C21ORF91 gene GRB2-RAS-RAF-MEK-ERK pathway GRB2-PI3K-AKT-GSK3β-β-catenin |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2020.605623/full |
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