Hsa_Circ_0066351 Acts as a Prognostic and Immunotherapeutic Biomarker in Colorectal Cancer

Abstract

Circular RNA (circRNA), a novel class of non-coding RNA, has been reported in various diseases, especially in tumors. However, the key signatures of circRNA-competitive endogenous RNA (ceRNA) network are largely unclear in colorectal cancer (CRC). We first characterized circRNAs profile by using circRNA-seq analysis from real-word dataset. The expression level of hsa_circ_0066351 in CRC tissues and cell lines was detected by quantitative real-time PCR. Then, cell proliferation assay was used to confirm the proliferation function of hsa_circ_0066351. Next, Cytoscape was used to construct circRNA–miRNA–mRNA networks. Last but not least, the landscape of hsa_circ_0066351–miRNA–mRNA in CRC had been investigated in the bulk tissue RNA-Seq level and single-cell Seq level. We proved that hsa_circ_0066351 was significantly downregulated in CRC cell lines and tissues (P < 0.001), and was negatively associated with distant metastasis (P < 0.01). Significantly, the expression of hsa_circ_0066351 was associated with better survival in patients with CRC. Function assays showed that hsa_circ_0066351 could inhibit CRC cells proliferation. In addition, a ceRNA network, including hsa_circ_0066351, two miRNAs, and ten mRNAs, was constructed. Our analyses showed that these ten mRNAs were consistently downregulated in pan-cancer and enriched in tumor suppressive function. A risk score model constructed by these ten downstream genes also indicated that they were related to the prognosis and immune response in CRC. In conclusion, we demonstrated that a novel circRNA (hsa_circ_0066351) inhibited CRC proliferation, and revealed a potential prognostic and immunotherapeutic biomarker in CRC.