Dataset Information

Circular RNA ATP2C1 (has_circ_0005797) sponges miR-432/miR-335 to promote breast cancer progression through regulating CCND1 expression.

ABSTRACT: Breast cancer (BC) is the most frequently diagnosed malignancy in the world. Accumulating evidence has indicated that circular RNAs (circRNAs) play essential roles in BC. Here we investigated the biological functions of circATP2C as a competing endogenous RNA (ceRNA) in BC development. We found that circATP2C1 expression was upregulated in BC cells and tissues and was significantly associated with the poor overall survival in BC patients. CircATP2C1 is more resistant to RNase R exonuclease and Actinomycin D than is the linear mRNA of ATP2C1. CircATP2C1-knockdown inhibited the viability, colony proliferation and invasion abilities, while increasing the apoptosis rates of BC cells in vitro, as well as inhibiting tumor mass, size and weight in vivo. Upregulation of miR-432 and miR-335 inhibited CCND1 expression in BC cells. Both miR-432/miR-335 specifically bind to the 3'-UTR of circATP2C1 and CCND1 (CyclinD1). The inhibition of the aggression of BC cells by circATP2C1-knockdown was rescued by co-transfection of miR-432/miR-335 inhibitors. In conclusion, circATP2C1 promotes BC oncogenesis and metastasis by sponging miR-432/miR-335 to abolish the inhibition of the target gene, CCND1. This study suggests that circATP2C1 has implications for BC diagnosis and treatment.

SUBMITTER: Chen C

PROVIDER: S-EPMC10492110 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Circular RNA ATP2C1 (has_circ_0005797) sponges miR-432/miR-335 to promote breast cancer progression through regulating CCND1 expression.

Chen Caiping C Lu Jianju J Li Wang W Lu Xiang X

American journal of cancer research 20230815 8

Breast cancer (BC) is the most frequently diagnosed malignancy in the world. Accumulating evidence has indicated that circular RNAs (circRNAs) play essential roles in BC. Here we investigated the biological functions of circATP2C as a competing endogenous RNA (ceRNA) in BC development. We found that circATP2C1 expression was upregulated in BC cells and tissues and was significantly associated with the poor overall survival in BC patients. CircATP2C1 is more resistant to RNase R exonuclease and A ...[more]

PMID: 37693160

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Project description:BackgroundGastric cancer (GC) is the third-leading cause of cancer-associated mortalities globally. The deregulation of circular RNAs (circRNAs) and microRNAs (miRNAs or miRs) is widely implicated in the pathogenesis and progression of different cancer types.MethodsThe expression profiling of circRNAs in GC is required to identify crucial circRNAs as biomarkers or therapeutic targets. In the present study, a published circRNA microarray dataset was used to identify differentially expressed circRNAs between GC tissues and normal gastric mucosa tissues. Reverse transcription-quantitative PCR was performed to validate the expression of circ_0001789. Fisher's exact test, receiver operating characteristic curve and Kaplan-Meier plots were employed to analyze the clinical significance of circ_0001789. The miRNA targets of circ_0001789 were predicted using an online database, and their functional interaction was further confirmed by RNA pull-down, RNA immunoprecipitation and dual luciferase reporter assays. Transwell assays were conducted to investigate the biological functions of circ_0001789, miR-140-3p and p21 activated kinase 2 (PAK2) in the migration and invasion of GC cells. A xenograft mouse model was established to validate the role of circ_0001789 in the tumorigenesis of GC cells.Resultscirc_0001789 was identified as a highly expressed circRNA in GC tissues versus normal gastric mucosa tissues. Silencing circ_0001789 attenuated the malignancy of GC cells, and exosomal circ_0001789 was sufficient to regulate the malignant phenotype of GC cells. miR-140-3p was further identified as a downstream target of circ_0001789, which showed a negative correlation with circ_0001789 expression in GC tissues. Overexpression of miR-140-3p suppressed cell migration, invasion and epithelial-mesenchymal transition in GC cells. PAK2 was identified as the target of miR-140-3 to mediate the malignant phenotype of GC cells.ConclusionThe present data suggested that the upregulation of circ_0001789 was associated with the progression of GC and with poor prognosis in patients with GC, and that miR-140-3p/PAK2 served as the downstream axis to mediate the oncogenic effect of circ_0001789.

Dataset Information

Circular RNA ATP2C1 (has_circ_0005797) sponges miR-432/miR-335 to promote breast cancer progression through regulating CCND1 expression.

Publications

Circular RNA ATP2C1 (has_circ_0005797) sponges miR-432/miR-335 to promote breast cancer progression through regulating CCND1 expression.

Similar Datasets

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