Expression and functional characterization of lncRNA SNHG4 in colorectal cancer

Long noncoding RNA SNHG4 has been implicated in colorectal cancer (CRC), but its expression across independent clinical cohorts and its contribution to CRC-related cellular phenotypes remain incompletely understood. SNHG4 expression was evaluated in GSE87211, TCGA-READ, TCGA-COAD, and paired specimens from a local CRC cohort. Clinicopathological associations were explored, and the effects of SNHG4 depletion were examined in HT29 and SW620 cells and in a subcutaneous xenograft model. Changes in miR-125a-3p and IGF2 expression were measured after RNA manipulation. Luciferase reporter assays assessed sequence responsiveness, and rescue experiments examined whether miR-125a-3p and IGF2 contributed to the phenotypes observed after SNHG4 depletion. SNHG4 expression was higher in rectal tumors in GSE87211 and TCGA-READ, in colon tumors in TCGA-COAD, and in local paired CRC specimens. In the local cohort, high SNHG4 expression was associated with larger tumor diameter and lymph-node metastasis in exploratory univariable analyses. SNHG4 depletion reduced CRC-cell viability, colony formation, wound closure, Transwell migration and invasion, and subcutaneous xenograft growth. SNHG4 and miR-125a-3p showed reciprocal expression changes and sequence-dependent reporter responses. IGF2 responded to miR-125a-3p, and IGF2 silencing attenuated the phenotypic rescue produced by miR-125a-3p inhibition in SNHG4-depleted cells. SNHG4 was consistently elevated in the CRC cohorts examined and was associated with growth- and motility-related phenotypes in CRC models. The reporter and rescue findings further identify miR-125a-3p and IGF2 as plausible contributors to these SNHG4-associated effects. Together, the data support SNHG4 as a candidate regulator of CRC-related phenotypes and provide a basis for further mechanistic investigation.