Abstract
Numerous studies have demonstrated that lncRNAs participate in regulatory networks of different cancers. Dysregulation of various lncRNAs such as DUXAP8, LINC00963, and FOXD2-AS1 has been reported in the development of various cancers. The aim of this study was investigation of the importance and potential roles of DUXAP8, LINC00963, and FOXD2-AS1 in ER+ breast cancer (BC). We examined the expression levels of DUXAP8, LINC00963, and FOXD2-AS1 in 71 luminal A and B tumor tissues and two luminal A cell lines (MCF7 and T47D) compared with adjacent non-tumor tissues and MCF10A cell line by qRT-PCR assay, respectively. For identifying the relation between three lncRNAs and luminal BC, bioinformatic analyses were performed using some databases and software including GENEVESTIGATOR software, GEPIA2, DAVID, REVIGO, STRING, lncATLAS, Kaplan–Meier plotter, starBase, and miRNet tool. The results showed the significant upregulation of all three lncRNAs in luminal A and B tumor specimens and cell lines. Upregulation of DUXAP8 and FOXD2-AS1 was significantly associated with progesterone receptor-positive (PR+) and p53 protein expression in luminal BC patients, respectively. Based on bioinformatic analyses, DUXAP8 can be considered as a prognostic biomarker for patients with luminal BC. DUXAP8, LINC00963, and FOXD2-AS1 are involved in several cancer-associated signaling pathways and multiple cancer-related processes. In addition, bioinformatic analyses indicated that LINC00963/hsa-mir-130a-3p/HSPA8 axis might have potential regulatory role in BC. In conclusion, dysregulation of DUXAP8, LINC00963, and FOXD2-AS1 can play roles in the development of luminal BC. They may exert their functions through involvement in some cancer signaling pathways and processes. In addition, they may interact with miRNAs like predicted interaction of LINC00963 with miR-130a-3p.
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Data availability
The datasets supporting the conclusions of this article are available in: [GEPIA2 web server] at (http://www.gepia.cancer-pku.cn); [GENEVESTIGATOR software] at (https://genevestigator.com); [DAVID database] at (https://david.ncifcrf.gov); [REVIGO database] at (http://revigo.irb.hr); [Cytoscape software] at (http://www.cytoscape.org); [STRING database] at (https://string-db.org); [lncATLAS] at (https://lncatlas.crg.eu); [starBase database] at (http://starbase.sysu.edu.cn); [miRNet tool] at (http://www.mirnet.ca); [Kaplan–Meier plotter database] at (http://kmplot.com/analysis). Citation of all data is provided in the references list. The datasets supporting the conclusions of this article are also included within the article and its additional files.
Abbreviations
- BC:
-
Breast cancer
- BRCA:
-
Invasive breast carcinoma
- CeRNA:
-
Competing endogenous RNA
- DUXAP8:
-
Double homeobox A pseudogene 8
- ER:
-
Estrogen receptor
- FOXD2-AS1:
-
FOXD2 adjacent opposite strand RNA 1
- GO:
-
Gene ontology
- HER2:
-
Human epidermal growth factor receptor 2
- LncRNA:
-
Long noncoding RNAs
- LINC00963:
-
Long intergenic non-protein coding RNA 963
- PR:
-
Progesterone receptor
- BCRC-BB:
-
Breast Cancer Research Center Bio-bank
- BP:
-
Biological process
- CC:
-
Cellular component
- MF:
-
Molecular function
- qRT-PCR:
-
Real-time quantitative reverse transcription-polymerase chain reaction
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Acknowledgements
We thank Dr. Rezvan Esmaeili (Head of Genetics Department, Breast Cancer Research Center of Motamed Cancer Institute, ACECR, Tehran, Iran) and Narges Jafarbeik Iravani for guidance of the experimental tests and other members of Genetics Department of Breast Cancer Research Center of Motamed Cancer Institute, ACECR, Tehran, Iran. In addition, the authors would like to thank Ms. Marzie Samimifar for proofreading the English language of the manuscript.
Funding
This work was supported by Faculty of Medicine, Tehran University of Medical Sciences (TUMS). The samples were obtained from Breast Cancer Research Center Bio-bank (BCRC-BB).
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M.A. performed experimental study and data analysis, bioinformatic analysis, literature review and wrote the manuscript. S.M. contributed to experimental study and data analysis and edited the manuscript. J.T.B. designed the research strategy, performed literature review, edited the manuscript, and reviewed the manuscript. M.M.N. performed statistical analysis and edited the manuscript. K.M. designed the research strategy, performed literature review, edited the manuscript and reviewed the manuscript. A.S. supervised the whole project and designed the research strategy, performed literature review, edited the manuscript and reviewed the manuscript. All the authors read and approved the final manuscript.
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The present study was approved by the Ethics Committee of Tehran University of Medical Sciences (TUMS) and written informed consent was obtained from all the participants (Code of Ethics: IR.TUMS.MEDICINE.REC.1398.659).
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13577_2021_539_MOESM1_ESM.pdf
Supplementary file1 Fig. S1. The summarization of gene ontology (GO) terms related to the co-expressed genes with DUXAP8 retrieved from REVIGO. (PDF 357 KB)
13577_2021_539_MOESM2_ESM.pdf
Supplementary file2 Fig. S2. The summarization of gene ontology (GO) terms related to the co-expressed genes with LINC00963 retrieved from REVIGO. (PDF 318 KB)
13577_2021_539_MOESM3_ESM.pdf
Supplementary file3 Fig. S3. The summarization of gene ontology (GO) terms related to the co-expressed genes with FOXD2-AS1 retrieved from REVIGO. (PDF 391 KB)
13577_2021_539_MOESM4_ESM.xlsx
Supplementary file4 Data S1. The genes were co-expressed with DUXAP8, LINC00963, and FOXD2-AS1 across luminal subtypes of multiple BC datasets obtained from GENEVESTIGATOR. (XLSX 37 KB)
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Supplementary file5 Data S2. The potential binding miRNAs for DUXAP8, LINC00963, and FOXD2-AS1 retrieved from starbase database. (XLSX 17 KB)
13577_2021_539_MOESM7_ESM.xlsx
Supplementary file7 Data S4. 321 of 399 potential target genes have strong interactions with each other based on STRING database. (XLSX 32 KB)
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Arabpour, M., Layeghi, S.M., Bazzaz, J.T. et al. The potential roles of lncRNAs DUXAP8, LINC00963, and FOXD2-AS1 in luminal breast cancer based on expression analysis and bioinformatic approaches. Human Cell 34, 1227–1243 (2021). https://doi.org/10.1007/s13577-021-00539-7
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DOI: https://doi.org/10.1007/s13577-021-00539-7