IGFL2-AS1-induced suppression of HIF-1α degradation promotes cell proliferation and invasion in colorectal cancer by upregulating CA9

Purpose: The lncRNA IGFL2-AS1 is a known cancer-promoting factor in colorectal Cancer (CRC); nonetheless, the mechanism of its carcinogenic effects has not yet been elucidated. This study elaborated on the role and underlying molecular mechanism of IGFL2-AS1 in promoting CRC cell functions.

Methods: IGLF2-AS1 expression levels in CRC tissue/normal tissue and CRC cell line/normal colon epithelial cell line were detected by quantitative real-time polymerase chain reaction. Cell counting kit-8, colony formation assay, and EdU assay were performed to assess the effect of IGFL2-AS1 knockdown or overexpression on the proliferative capacity of CRC cells. The migration and invasion abilities of LoVo cells were measured using transwell assay. The expression relationship between IGFL2-AS1 and Carbonic Anhydrase 9 (CA9) and the CA9 expression level in CRC tissues and cells was verified by transcriptome sequencing, western blotting, and immunohistochemical staining. Treatment with MG132 and cycloheximide was utilized to explore the mechanism by which IGFL2-AS1 affects the hypoxia-inducible factor-1α (HIF-1α)/CA9 pathway. A nude mouse xenograft model was constructed to evaluate the effect of IGFL2-AS1 on CRC growth in vivo.

Results: We discovered that IGFL2-AS1 was highly upregulated in CRC tumor tissues and cells. IGFL2-AS1 can functionally promote CRC cell proliferation, migration, and invasion in vitro and accelerate CRC occurrence in vivo. Mechanistic studies demonstrated that IGFL2-AS1 upregulated the CA9 level by affecting the degradation pathway of HIF-1α, which elucidates its pro-proliferative effect in CRC. The lncRNA IGFL2-AS1 mediated the inhibition of HIF-1α degradation in CRC and increased CA9 expression, thereby promoting CRC progression.

Conclusion: Our findings suggested that IGFL2-AS1 is expected to be a promising new diagnostic marker and therapeutic target for CRC.

CA9; HIF-1α; IGFL2-AS1; colorectal cancer; degradation.