Search

Background: Circular RNAs (circRNAs) take an effect on tumorigenesis and progression. However, circRNAs have not been systematically identified in breast cancer (BC) as crucial regulators in multitudinous biological processes. This study is conducted to explore novel circRNAs in BC and the corresponding mechanisms of their action. Methods: The circRNA expression profile and RNA-sequencing data about BC were respectively downloaded from public database. Differentially expressed circRNAs, miRNAs, and mRNAs were identified by fold change filtering. The competing endogenous RNAs (ceRNAs) network was established based on the relationship between circular RNAs, miRNAs and mRNAs. GO and KEGG enrichment analysis of the overlapped genes were carried out to predict the potential functions and mechanisms of circRNAs in BC. The CytoHubba plugin in Cytoscape was applied to identify the hub genes from the PPI regulatory network. Kaplan–Meier plotter was used to perform survival analysis of these hub genes further. Real-time PCR was performed to test the expression of circRNA in BC tissues. Cell function studies including transwell analysis and CCK-8 analysis were used to investigate circRNAs' biological functions. Results: A total of seven circRNAs exhibiting differential expression were identified in this study. After the intersection between the predicted target miRNA and the down-regulated differential miRNAs (DEmiRNAs), circRNA-miRNA interactions involving 3 circRNAs and 4 miRNAs were identified. Venn diagram was utilized to intersect the predicted target genes of the 4 miRNAs and the down-regulated differential genes in BC, and 149 overlapped genes were screened out ulteriorly. Additionally, we built a protein-protein interaction (PPI) network and selected six hub genes. Moreover, the survival data of BC patients suggested that low expression of ADIPOQ, LPL and LEP were significantly correlated with poor prognosis. Results from real-time PCR indicated that hsa_circ_0000375 was significantly down-regulated in breast cancer tissues. Functional in vitro experiments showed that over-expression of hsa_circ_0000375 can restrain proliferation, migration and invasion abilities of breast cancer cells. Further verification indicated that hsa_circ_0000375 exerted its anti-oncogene effect via sponge of miR-7706. Conclusions: This study constructed and analyzed a circRNA-associated ceRNA regulatory network and uncovered that hsa_circ_0000375 exerted its anti-oncogene effect via sponge of miR-7706. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is one of the leading causes of cancer-related deaths in women. The purpose of this study is to identify key molecular markers related to the diagnosis and prognosis of early breast cancer (EBC). The data of mRNA, lncRNA and DNA methylation were downloaded from The Cancer Genome Atlas (TCGA) dataset for identification of differentially expressed mRNAs (DEmRNAs), differentially expressed lncRNAs (DElncRNAs) and DNA methylation analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyzes were used to identify the biological functions of DEmRNAs. The correlation analysis between DNA methylation and DEmRNAs was carried out. Then, diagnostic analysis and prognostic analysis of identified DEmRNAs and DElncRNAs were also performed in the TCGA database. Subsequently, methylation state verification for identified DEmRNAs was performed in the GSE32393 dataset. In addition, real-time polymerase chain reaction (RT-PCR) in vitro verification of genes was performed. Finally, AC093110.1 was overexpressed in human BC cell line MCF-7 to verify cell proliferation and migration. In this study, a total of 1633 DEmRNAs, 750 DElncRNAs and 8042 differentially methylated sites were obtained, respectively. In the Venn analysis, 11 keys DEmRNAs (ALDH1L1, SPTBN1, MRGPRF, CAV2, HSPB6, PITX1, WDR86, PENK, CACNA1H, ALDH1A2 and MME) were we found. ALDH1A2, ALDH1L1, HSPB6, MME, MRGPRF, PENK, PITX1, SPTBN1, WDR86 and CAV2 may be considered as potential diagnostic gene biomarkers in EBC. Strikingly, CAV2, MME, AC093110.1 and AC120498.6 were significantly actively correlated with survival. Methylation state of identified DEmRNAs in GSE32393 dataset was consistent with the result in TCGA. AC093110.1 can affect the proliferation and migration of MCF-7. ALDH1A2, ALDH1L1, HSPB6, MME, MRGPRF, PENK, PITX1, SPTBN1, WDR86 and CAV2 may be potential diagnostic gene biomarkers of EBC. Strikingly, CAV2, MME, AC093110.1 and AC120498.6 were significantly actively correlated with survival. The identification of these genes can help in the early diagnosis and treatment of EBC. In addition, AC093110.1 can regulate SPTBN1 expression and play an important role in cell proliferation and migration, which provides clues to clarify the regulatory mechanism of EBC. [ABSTRACT FROM AUTHOR]

The correct affiliations are listed below: Affiliation 1: Department of Breast Center, The Fourth Hospital of Hebei Medical University, 169 Tianshan Street, Shijiazhuang, Hebei 050011, People's Republic of China Affiliation 2: Gland Surgery, Shijiazhuang People's Hospital, Shijiazhuang, People's Republic of China Furthermore, Affiliation 1 was omitted for Wenshan Zhang. Correction to: I Scientific Reports i https://doi.org/10.1038/s41598-022-05486-3, published online 07 February 2022 In the original version of this Article, Affiliation 1 and 2 were not listed in the correct order. [Extracted from the article]