CircRNA Sequencing Analysis Reveals the Regulatory Role of circ_CDR1as in Penile Squamous Cell Carcinoma via the ceRNA Network

TL;DR

This study explores how a specific circular RNA, circ_CDR1as, influences penile squamous cell carcinoma through a regulatory RNA network.

Contribution

The study identifies circ_CDR1as as a key regulator in PSCC and proposes GATA6 as a potential therapeutic target.

Findings

circ_CDR1as and GATA6 are significantly downregulated in PSCC tumor samples.

A ceRNA network involving 11 circRNAs, 14 miRNAs, and 33 mRNAs was constructed.

Downregulated mRNAs are linked to leukocyte activation and cell adhesion processes.

Abstract

Penile squamous cell carcinoma (PSCC) is a malignant reproductive tumor, and circRNAs are essential regulators in the progression of cancers. However, their specific roles in PSCC have not been adequately investigated, which are available to function via the competing endogenous RNA (ceRNA) network. We collected 5 normal and 6 PSCC tissue samples for bulk RNA sequencing and obtained differentially expressed circRNAs (DE-circRNAs) and differentially expressed mRNAs (DE-mRNAs). Then we conducted a correlation analysis between them, followed by the prediction and intersection of their target miRNAs and mRNAs by online databases. We constructed a ceRNA network of 11 circRNAs, 14 miRNAs, and 33 mRNAs. The enrichment analysis showed that the positively circRNA-related mRNAs are mainly involved in the positive regulation of leukocyte activation and cell adhesion. It was revealed that circ_CDR1as and its target gene GATA6 were significantly downregulated in PSCC, and their reduction in tumor samples was validated by an external dataset and qRT-PCR, indicating a potential regulatory relationship between them. Our study identified that circ_CDR1as may affect PSCC progression through the circRNA-miRNA-mRNA network, and GATA6 could be one of its possible targets for PSCC therapy strategies.

Figures