Deng Jun-Li, Zhang Hai-Bo, Zeng Ying, Xu Yun-Hua, Huang Ying, Wang Guo
Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, China.
Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, China.
Front Oncol. 2020 Jun 26;10:916. doi: 10.3389/fonc.2020.00916. eCollection 2020.
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 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.
冠蛋白2A（CORO2A）是核受体共抑制因子（N-CoR）复合物的一个新组分。CORO2A表达异常与肿瘤发生相关。我们使用了癌症基因组图谱（TCGA）和基因表达综合数据库（GEO），分析了乳腺癌中CORO2A的表达及基因调控网络。利用GEO和TCGA数据库分析其表达情况，并在我们诊所收集的乳腺癌样本中进一步验证。采用Kaplan-Meier生存分析和Cox比例风险回归分析探索CORO2A的预后价值。使用LinkedOmics软件识别与CORO2A共表达的基因。在分析与CORO2A相关的共表达基因与CORO2A沉默后差异表达基因的交集后，利用软件对交集基因进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析。在乳腺癌细胞中进行Transwell实验以确定CORO2A对细胞迁移的影响。在乳腺癌细胞中进行MTS、集落形成和细胞周期分布实验以确定CORO2A对细胞增殖的影响。采用基因富集分析探索转录因子和微小RNA（miRNA）的靶标网络。我们发现CORO2A在三阴乳腺癌（TNBC）患者中表达上调，且其表达升高与较差的总生存期（OS）和无复发生存期（RFS）相关。对公共测序数据和我们自己的RNA测序（RNA-Seq）数据进行的进一步生物信息学分析表明，CORO2A可能参与上皮-间质转化过程，并且可能对乳腺癌细胞的迁移有显著影响，这可能是通过涉及几种miRNA和MYC转录因子的途径介导的。在功能上，敲低CORO2A可抑制乳腺癌细胞的迁移、降低细胞活力和集落形成，并诱导细胞周期停滞于G0/G1期。这些结果表明，基于生物信息学的分析有效地揭示了乳腺癌中CORO2A表达及其潜在调控网络的信息，为进一步深入研究CORO2A在肿瘤发生中的作用机制奠定了基础。此外，CORO2A促进乳腺癌细胞的迁移和增殖，可能在乳腺癌进展中起重要作用。CORO2A是TNBC患者潜在的预后预测指标。靶向CORO2A可能为乳腺癌治疗提供有前景的治疗策略。
