The human microRNA 452 (MIR452) was identified as a colorectal cancer (CRC)-associated micro RNA (miRNA) by miRNA expression profiling of human CRC tissues versus normal colorectal tissues. It was significantly up-regulated in human CRC tissues. However, the functional mechanisms of MIR452 and its target genes in CRC remain unclear. We identified 27 putative MIR452 target genes, and found that the vascular endothelial growth factor A (VEGFA) was a direct target gene of MIR452. Both cellular and extracellular VEGFA levels were significantly downregulated in CRC cells upon their transfection with MIR452 or siVEGFA. VEGFA expression was frequently downregulated in human CRC tissues in comparison with that in their healthy counterparts. We showed that MIR452 regulated the expression of genes in the VEGFA-mediated signal transduction pathways vascular endothelial growth factor receptor 1 (VEGFR2)–mitogen-activated protein kinase (MAPK) and VEGFR2–SRC proto-oncogene non-receptor tyrosine kinase (SRC) in CRC cells. Immunohistological analyses of xenografted MIR452-overexpressing CRC cells in mice showed that MIR452 regulated cell proliferation and angiogenesis. Furthermore, aortic ring angiogenesis assay in rats clearly showed that the number of microvessels formed was significantly reduced by MIR452 transfection. Our findings suggest that MIR452 regulates cell proliferation, cell migration, and angiogenesis by suppressing VEGFA expression in early CRC progression; therefore, MIR452 may have therapeutic value in relation to human CRC.

Background/Objectives: Colorectal cancer (CRC) is one of the most common cancers worldwide, with high incidence and mortality rates. MicroRNAs are endogenous and non-coding RNAs that play a pivotal role in the development and progression of various cancers by targeting specific genes. Previously, we identified MIR133A to be significantly decreased in human CRC tissues. This study aims to identify the relationship with SQLE, one of the candidate target genes of MIR133A, and study their interaction in CRC cells. Methods: Through the luciferase reporter assay, quantitative RT-PCR (qRT-PCR), and Western blot analysis. Results: We identified SQLE as a direct target gene of MIR133A. Using the MIR133A KI cell lines, which knocked-in MIR133A1 or MIR133A2 in CRC cell lines, and CRC cells transfected with siSQLE, we found that MIR133A regulated the proliferation and migration of CRC cells by modulating SQLE-mediated PIK3CA-AKT1 and CYP24A1 signaling. We also found that cholesterol production was regulated by MIR133A in CRC cells. Conclusions: Our results suggest that MIR133A is an important therapeutic target for colorectal cancer.

MicroRNAs (miRNAs) play important roles in the regulation of gene expression and are frequently dysregulated in cancer. Among them, the miR-196 family has been implicated in multiple malignancies, including colorectal cancer (CRC), but the isoform-specific transcriptional effects of miR-196A and miR-196B remain poorly understood. In this study, we generated miR-196A and miR-196B knockout SW48 CRC cell lines using CRISPR-based genome editing and performed RNA sequencing to investigate the transcriptional consequences of individual miR-196 isoform deletion. Transcriptomic analysis revealed widespread gene expression changes in both knockout models and demonstrated distinct clustering patterns between parental SW48 cells and miR-196-deficient cells. Functional enrichment analysis indicated that the altered genes were associated with biological processes related to cytoskeletal organization, intracellular transport, protein folding, and metabolic regulation. Notably, both shared and isoform-specific transcriptional alterations were observed, suggesting that miR-196A and miR-196B contribute to partially overlapping but distinct regulatory networks in CRC cells. Collectively, these findings provide a comprehensive transcriptomic overview of miR-196 isoform deletion in colorectal cancer cells and highlight potential isoform-dependent transcriptional programs that may contribute to CRC biology.

Background: MicroRNA-133 (miR-133) has been implicated in diverse cancers as a tumor suppressor, yet the isoform-specific contributions of miR-133A1, miR-133A2, and miR-133B in colorectal cancer (CRC) remain unclear. Methods: We established stable colorectal cancer cell lines expressing each miR-133 isoform and performed iso-form-level transcriptomic profiling. Differentially expressed genes (DEGs) were iden-tified relative to parental cells and subjected to gene ontology (GO) and KEGG en-richment analyses. Comparative analyses highlighted both shared and distinct bio-logical pathways regulated by each isoform. Results: Venn diagram and clustering analyses revealed that all three isoforms shared a core regulatory program, with 34 genes consistently upregulated and 195 genes downregulated across all isoforms, while also displaying isoform-specific DEGs. miR-133A1 and miR-133A2 showed strong transcriptional similarity, predominantly modulating extracellular matrix or-ganization, cell migration, and apoptotic pathways. In contrast, miR-133B exhibited a distinct expression profile, preferentially influencing RNA processing, immune sup-pression, and oncogenic signaling pathways including PI3K-Akt, Hippo, and p53 sig-naling. Heatmap analysis of representative genes confirmed both overlapping and isoform-specific expression changes, with survival- and proliferation-associated genes more strongly upregulated in miR-133A2 and miR-133B. Conclusion: These findings suggest that miR-133 isoforms exert both shared and divergent regulatory functions in colorectal cancer, coordinating apoptosis, proliferation, migration, and signaling net-work modulation. Isoform-specific transcriptional regulation of miR-133 may contrib-ute to tumor progression and represents a potential biomarker and therapeutic target in CRC.

Background: MicroRNA-133 (miR-133) has been implicated in diverse cancers as a tumor suppressor, yet the isoform-specific contributions of miR-133A1, miR-133A2, and miR-133B in colorectal cancer (CRC) remain unclear. Methods: We established stable colorectal cancer cell lines expressing each miR-133 isoform and performed isoform-level transcriptomic profiling. Differentially expressed genes (DEGs) were identified relative to parental cells and subjected to gene ontology (GO) and KEGG enrichment analyses. Comparative analyses highlighted both shared and distinct biological pathways regulated by each isoform. Results: Venn diagram and clustering analyses revealed that all three isoforms shared a core regulatory program, with 34 genes consistently upregulated and 195 genes downregulated across all isoforms, while also displaying isoform-specific DEGs. miR-133A1, miR-133A2, and miR-133B showed predominantly convergent transcriptional programs, with subtle quantitative differences observed primarily in KI133B. Heatmap analysis of representative genes confirmed both overlapping and isoform-specific expression changes, with survival- and proliferation-associated genes more strongly upregulated in miR-133A2 and miR-133B. Conclusion: These findings suggest that miR-133 isoforms exert both shared and subtly divergent regulatory functions in colorectal cancer, coordinating apoptosis, proliferation, migration, and signaling network modulation. Isoform-specific transcriptional regulation of miR-133 may contribute to tumor progression and represents a potential biomarker and therapeutic target in CRC.