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CircRAPGEF5 acts as a modulator of RAS/RAF/MEK/ERK signaling during colorectal carcinogenesis

ABSTRACT: Mutations in oncogenes such as KRAS, NRAS and BRAF promote cancer cell survival and proliferation, while excessive RAS/RAF/MEK/ERK signaling instead exerts an inhibitory effect on tumor growth. The precise regulatory mechanism of moderate RAS/RAF/MEK/ERK pathway activation during tumorigenesis remains elusive. Here, we discovered that a circular RNA, circRAPGEF5, was significantly upregulated in KRAS mutant colorectal cancer (CRC) cells. CircRAPGEF5 suppressed mutant and constitutively activated KRAS and the expression of the death receptor TNFRSF10A. Silencing of circRAPGEF5 induced RAS/RAF/MEK/ERK signaling hyperactivation and apoptosis in CRC cells. Moreover, the circularization of circRAPGEF5 was promoted by EIF4A3, whose expression was also elevated in tumor tissues. Taken together, our findings reveal a mechanism of accurate regulation of RAS/RAF/MEK/ERK signaling during CRC progression and provide potential targets for cancer therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE269456 | GEO | 2026/06/13

REPOSITORIES: GEO

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