circEIF3I Promotes Colorectal Cancer Metastasis by Regulating the miR-328-3p/NCAPH Axis.

Abstract

Colorectal cancer (CRC) is the most common gastrointestinal malignancy, with its recurrence and metastasis significantly affecting patient survival. Circular RNAs (circRNAs), a novel class of noncoding RNAs, have emerged as crucial contributors to CRC pathogenesis. However, the role of circEIF3I in CRC metastasis remains unclear. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to assess circEIF3I, microRNA (miR)-328-3p, and NCAPH expression. CRC cell migration and invasion were determined via Transwell assays. Western blot analysis was utilized to define the protein expression of epithelial-mesenchymal transition (EMT) markers and NCAPH. Xenograft tumor was established for exploration into the function of circEIF3I in CRC metastasis to the liver and lung. The binding between miR-328-3p and circEIF3I or NCAPH was predicted through ENCORI or TargetScan platform and ascertained through dual-luciferase reporter assays. circEIF3I and NCAPH expression were found to be elevated in CRC tissues and cells, while miR-328-3p was downregulated. Functionally, circEIF3I knockdown inhibited CRC cell migration, invasion, EMT, and tumor metastasis. Mechanistic analyses revealed that circEIF3I can target miR-328-3p, while NCAPH was targeted by miR-328-3p. Furthermore, circEIF3I facilitated NCAPH expression in CRC cells by sequestering miR-328-3p. Notably, miR-328-3p inhibitor or NCAPH overexpression negated the effects of circEIF3I knockdown on preventing CRC progression in vitro. Taken together, circEIF3I elevated NCAPH expression by sponging miR-328-3p, thereby promoting CRC metastasis. These findings suggest that the circEIF3I/miR-328-3p/NCAPH axis represents a novel therapeutic target for CRC.