Circular RNAs (circRNAs) have been implicated in the pathogenesis and metastasis of colorectal cancer (CRC). However, the functional roles and clinical diagnostic potential of most circRNAs in CRC remain largely unknown. This study aimed to identify differentially expressed circRNAs (DEcircRNAs) and construct a potential competing endogenous RNA (ceRNA) network, investigating the relationship between mRNA expression and immune infiltration to identify novel biomarkers for CRC diagnosis and therapy. Quantitative real-time PCR (qRT-PCR) was used to validate circRNA expression in CRC tissues and cell lines. Survival outcomes were compared by hsacirc₀007158 expression using Kaplan-Meier analysis with the log-rank test. Functional assays, including CCK-8, migration, invasion, and flow cytometry, were conducted in CRC cell lines to investigate the roles of candidate circRNAs. To further explore the underlying ceRNA network, we measured miRNA and mRNA expression following circRNA knockdown using qRT-PCR and analyzed the correlation between predicted mRNAs and immune cell infiltration via database mining. Hsacirc₀007158 was significantly upregulated in CRC cell lines and patient tissues, and its expression was positively associated with advanced clinicopathological features and poor prognosis. Functional experiments demonstrated that knockdown of hsacirc₀007158 inhibited CRC cell proliferation and migration, arrested cell cycle progression, and promoted apoptosis. In hsacirc₀007158-silenced cells, miR-181a-2-3p expression was significantly increased, while TRAF1 and WIPI2 expression was downregulated. CircRNA expression was positively correlated with target genes and negatively correlated with miRNAs, consistent with the ceRNA hypothesis. Furthermore, target gene expression was correlated with the infiltration levels of specific immune cells. Our findings indicate that hsacirc₀007158 acts as an oncogene in CRC progression. This study proposes a novel ceRNA network and reveals correlations between target genes and immune cell infiltration, providing new insights for CRC diagnosis and targeted therapy.
Fang et al. (Sat,) studied this question.