Abstract
Coronin 2A (CORO2A) is a novel component of the N-CoR (nuclear receptor co-repressor) complex. Abnormal CORO2A expression is associated with carcinogenesis. We used databases from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and analyzed CORO2A expression and gene regulation networks in breast cancer. Expression was analyzed using GEO and TCGA database and further validated in breast cancer samples collected in our clinic. The prognostic value of CORO2A was explored by using the Kaplan–Meier survival analysis and Cox proportional hazards regression analysis. LinkedOmics was used to identify coexpressed genes associated with CORO2A. After analyzing the intersection of coexpressed genes correlated with CORO2A and differentially expressed genes after CORO2A silencing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the intersecting genes were conducted by using FunRich software. Transwell assays were performed in breast cancer cells to determine the effect of CORO2A on cell migration. MTS, colony formation, and cell cycle distribution assays were performed in breast cancer cells to determine the effect of CORO2A on cell proliferation. Gene enrichment analysis was employed to explore the target networks of transcription factors and miRNAs. We found that CORO2A was upregulated and that the elevated expression of CORO2A was associated with poor overall survival (OS) and relapse-free survival (RFS) in TNBC patients. Further bioinformatics analysis of public sequencing data and our own RNA-Seq data revealed that CORO2A was probably involved in the epithelial-to-mesenchymal transition process and might have a significant effect on the migration of breast cancer cells, which might be mediated via pathways involving several miRNAs and MYC transcription factors. Functionally, the knockdown of CORO2A inhibited cell migration, decreased viability, and colony formation and induced cell cycle arrest in the G0/G1 phase in breast cancer cells. These results demonstrate that bioinformatics-based analysis efficiently reveals information about CORO2A expression and its potential regulatory networks in breast cancer, laying a foundation for further mechanistic research on the role of CORO2A in carcinogenesis. Moreover, CORO2A promotes the migration and proliferation of breast cancer cells and may have an important function in breast cancer progression. CORO2A is a potential prognostic predictor for TNBC patients. Targeting CORO2A may provide promising therapy strategies for breast cancer treatment.
Highlights
Breast cancer is reported to be the most common malignancy in women, with an estimated 268,600 new cases and 41,760 deaths in 2019, which represents 30% of all new cancer cases and 15% of cancer-related deaths among American women [1, 2]
By using four public datasets from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), we found that Coronin 2A (CORO2A) was overexpressed in malignant breast tissues compared to normal breast tissues [4]
Since the LinkFinder module of LinkedOmics allows users to search for attributes that are associated with a query attribute, such as mRNA, we investigated genes that were differentially expressed in correlation with CORO2A in the TCGA breast cancer cohort
Summary
Breast cancer is reported to be the most common malignancy in women, with an estimated 268,600 new cases and 41,760 deaths in 2019, which represents 30% of all new cancer cases and 15% of cancer-related deaths among American women [1, 2]. Breast cancer is a complex disease with cumulative genetic and epigenetic aberrations as well as cancer cell heterogeneity [3]. Understanding these pathological molecular alterations has significant implications in cancer initiation and progression as well as in cancer prevention and treatment. Fridley et al [9] observed shorter progression-free survival (PFS) in endometrioid carcinoma and clear cell carcinoma patients with high gene expression for CORO2A. Based on these studies, we studied the function and prognostic significance of CORO2A in breast cancer
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