In‐silico and in‐vitro evidence suggest LINC01405 as a sponge for miR‐29b and miR‐497‐5p, and a potential regulator of Wnt, PI3K, and TGFB signaling pathways in breast carcinoma
Abstract Background Carcinoma of the breast, a prevailing factor in female mortality worldwide, involves dysregulation of lncRNAs and microRNAs. Aim The main goal of this research was to predict and experimentally examine the LINC01405 expression status in breast cancer subtypes, along with investig...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Cancer Reports |
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| Online Access: | https://doi.org/10.1002/cnr2.1972 |
| _version_ | 1797292548129030144 |
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| author | Romina Norouzi Zahra Mohamadzade Rambod Norouzi Radin Norouzi Rezvan Esmaeili Bahram M. Soltani |
| author_facet | Romina Norouzi Zahra Mohamadzade Rambod Norouzi Radin Norouzi Rezvan Esmaeili Bahram M. Soltani |
| author_sort | Romina Norouzi |
| collection | DOAJ |
| description | Abstract Background Carcinoma of the breast, a prevailing factor in female mortality worldwide, involves dysregulation of lncRNAs and microRNAs. Aim The main goal of this research was to predict and experimentally examine the LINC01405 expression status in breast cancer subtypes, along with investigation of its interaction with miR‐29b and miR‐497‐5p that results in regulating PI3‐Kinase, WNT, and TGF‐beta signaling pathways. Methods and Results We performed a meta‐analysis of five GEO datasets, encompassing microarray and RNA‐seq data, to identify differentially expressed genes. The Cancer Genome Atlas transcriptome dataset was also analyzed to determine essential gene modules, associated with different stages of breast cancer by weighted gene co‐expression networks. In addition, networks of drug‐gene interactions were constructed to explore potential treatment options. LINC01405 as a microRNA sponge was chosen and examined. furthermore, downstream target genes were discovered. Experimental validation consisted of plasmid constructs used in cell culture experiments, RT‐qPCR for expression analysis, and cell cycle assays. Our bioinformatics findings showed higher LINC01405 expression in Basal‐like triple‐negative breast carcinoma. In contrast, lower expression in Luminal samples was observed compared with normal samples, which was consistently observed in both breast cancer tissues and cell lines. LINC01405 expression level was correlated with miR‐29b and miR‐497 levels. The MDA‐MB‐231 cell line demonstrated higher LINC01405 expression and lower miR‐29b and miR‐497 expression levels. However, SKBR3 and MCF7 cells had lower LINC01405 expression and higher miR‐29b and miR‐497 levels, suggesting a regulatory role for LINC01405 as a competing endogenous RNA. This was experimentally confirmed when LINC01405 was overexpressed in SKBR3 cells, and the common target genes of miR‐29b and miR‐497 were upregulated. Additionally, LINC01405 upregulation led to the increased cell populations, proliferation, and upregulation of critical cancer‐related genes, including AKT1, AKT3, mTOR, WNT3A, SMAD3, CYCLIN D1, CYCLIN D2, BCL2, and GSK3B. Conclusion We revealed the differential expression of LINC01405 in several types of breast cancer and its role in regulating signaling pathways, potentially via scavenging miRNAs. These findings clarified the role of LINC01405 in breast cancer development and identified potential therapeutic targets. |
| first_indexed | 2024-03-07T19:58:01Z |
| format | Article |
| id | doaj.art-5dd9c16b994a47a0a1f4f662448d6bb8 |
| institution | Directory Open Access Journal |
| issn | 2573-8348 |
| language | English |
| last_indexed | 2024-03-07T19:58:01Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Reports |
| spelling | doaj.art-5dd9c16b994a47a0a1f4f662448d6bb82024-02-28T13:54:58ZengWileyCancer Reports2573-83482024-02-0172n/an/a10.1002/cnr2.1972In‐silico and in‐vitro evidence suggest LINC01405 as a sponge for miR‐29b and miR‐497‐5p, and a potential regulator of Wnt, PI3K, and TGFB signaling pathways in breast carcinomaRomina Norouzi0Zahra Mohamadzade1Rambod Norouzi2Radin Norouzi3Rezvan Esmaeili4Bahram M. Soltani5Molecular Genetics Department, Faculty of Biological Sciences Tarbiat Modares University Tehran IranMolecular Genetics Department, Faculty of Biological Sciences Tarbiat Modares University Tehran IranMolecular Biosciences Department Autonomous University of Madrid Madrid SpainBiology Department Kharazmi University Tehran IranGenetics Department, Center for Breast Cancer Research Motamed Cancer Institute Tehran IranMolecular Genetics Department, Faculty of Biological Sciences Tarbiat Modares University Tehran IranAbstract Background Carcinoma of the breast, a prevailing factor in female mortality worldwide, involves dysregulation of lncRNAs and microRNAs. Aim The main goal of this research was to predict and experimentally examine the LINC01405 expression status in breast cancer subtypes, along with investigation of its interaction with miR‐29b and miR‐497‐5p that results in regulating PI3‐Kinase, WNT, and TGF‐beta signaling pathways. Methods and Results We performed a meta‐analysis of five GEO datasets, encompassing microarray and RNA‐seq data, to identify differentially expressed genes. The Cancer Genome Atlas transcriptome dataset was also analyzed to determine essential gene modules, associated with different stages of breast cancer by weighted gene co‐expression networks. In addition, networks of drug‐gene interactions were constructed to explore potential treatment options. LINC01405 as a microRNA sponge was chosen and examined. furthermore, downstream target genes were discovered. Experimental validation consisted of plasmid constructs used in cell culture experiments, RT‐qPCR for expression analysis, and cell cycle assays. Our bioinformatics findings showed higher LINC01405 expression in Basal‐like triple‐negative breast carcinoma. In contrast, lower expression in Luminal samples was observed compared with normal samples, which was consistently observed in both breast cancer tissues and cell lines. LINC01405 expression level was correlated with miR‐29b and miR‐497 levels. The MDA‐MB‐231 cell line demonstrated higher LINC01405 expression and lower miR‐29b and miR‐497 expression levels. However, SKBR3 and MCF7 cells had lower LINC01405 expression and higher miR‐29b and miR‐497 levels, suggesting a regulatory role for LINC01405 as a competing endogenous RNA. This was experimentally confirmed when LINC01405 was overexpressed in SKBR3 cells, and the common target genes of miR‐29b and miR‐497 were upregulated. Additionally, LINC01405 upregulation led to the increased cell populations, proliferation, and upregulation of critical cancer‐related genes, including AKT1, AKT3, mTOR, WNT3A, SMAD3, CYCLIN D1, CYCLIN D2, BCL2, and GSK3B. Conclusion We revealed the differential expression of LINC01405 in several types of breast cancer and its role in regulating signaling pathways, potentially via scavenging miRNAs. These findings clarified the role of LINC01405 in breast cancer development and identified potential therapeutic targets.https://doi.org/10.1002/cnr2.1972breast cancerdifferential expressionLINC01405sponge |
| spellingShingle | Romina Norouzi Zahra Mohamadzade Rambod Norouzi Radin Norouzi Rezvan Esmaeili Bahram M. Soltani In‐silico and in‐vitro evidence suggest LINC01405 as a sponge for miR‐29b and miR‐497‐5p, and a potential regulator of Wnt, PI3K, and TGFB signaling pathways in breast carcinoma Cancer Reports breast cancer differential expression LINC01405 sponge |
| title | In‐silico and in‐vitro evidence suggest LINC01405 as a sponge for miR‐29b and miR‐497‐5p, and a potential regulator of Wnt, PI3K, and TGFB signaling pathways in breast carcinoma |
| title_full | In‐silico and in‐vitro evidence suggest LINC01405 as a sponge for miR‐29b and miR‐497‐5p, and a potential regulator of Wnt, PI3K, and TGFB signaling pathways in breast carcinoma |
| title_fullStr | In‐silico and in‐vitro evidence suggest LINC01405 as a sponge for miR‐29b and miR‐497‐5p, and a potential regulator of Wnt, PI3K, and TGFB signaling pathways in breast carcinoma |
| title_full_unstemmed | In‐silico and in‐vitro evidence suggest LINC01405 as a sponge for miR‐29b and miR‐497‐5p, and a potential regulator of Wnt, PI3K, and TGFB signaling pathways in breast carcinoma |
| title_short | In‐silico and in‐vitro evidence suggest LINC01405 as a sponge for miR‐29b and miR‐497‐5p, and a potential regulator of Wnt, PI3K, and TGFB signaling pathways in breast carcinoma |
| title_sort | in silico and in vitro evidence suggest linc01405 as a sponge for mir 29b and mir 497 5p and a potential regulator of wnt pi3k and tgfb signaling pathways in breast carcinoma |
| topic | breast cancer differential expression LINC01405 sponge |
| url | https://doi.org/10.1002/cnr2.1972 |
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