Gastrointestinal (GI) cancers are some of the most common cancers in the world and their number is increasing. Their etiology and pathogenesis are still unclear. ADAM proteins are a family of transmembrane and secreted metalloproteinases that play a role in cancerogenesis, metastasis and neoangiogenesis. MicroRNAs are small single-stranded non-coding RNAs that take part in the post-transcriptional regulation of gene expression. Some ADAM proteins can be targets for microRNAs. In this review, we analyze the impact of microRNA/ADAM protein axes in GI cancers.

The role of adamalysins (ADAMs) has been widely described in many processes related to carcinogenesis, angiogenesis, inflammation, metastasis, and metabolic disorders. Despite numerous studies, their role in colorectal cancer (CRC) remains unclear. The aim of this study was to evaluate the expression of selected ADAM genes in colorectal cancer tissue and corresponding surgical margins. In addition, for a subgroup of patients, the expression of selected proteins from the ADAM family was assessed. The final study group consisted of 67 patients who underwent elective surgery for colorectal cancer. The relative expression of the ADAM10, 12, 17, and 28 genes was expressed as relative quantification (RQ) and determined by real-time quantitative PCR (RT-qPCR) in tumor tissue and surgical margins. In addition, for a subgroup of 45 patients, the expression of ADAM10, 12, and 17 proteins was assessed by ELISA. Associations between ADAM expression and clinicopathological parameters were analyzed statistically. ADAM12 gene expression was significantly higher in tumor than in margin tissue (median RQ: 0.995 vs. 0.251; p = 0.003), whereas ADAM28 RQ was significantly higher in the margin (median RQ: 0.400 vs. 0.204; p = 0.021). No significant differences were observed in the expression of the ADAM10, ADAM12, ADAM17, or ADAM28 genes based on tumor stage, sex, substance use, BMI, or age, except for nominally higher ADAM12 gene expression in patients over 65 years of age (p = 0.033). Among patients under 65 years of age with cardiovascular disease (CVD), ADAM28 RQ in tumor tissue was significantly higher than in those without CVD (p < 0.05). In obese patients with CVD, a markedly increased expression of ADAM28 in tumor tissue was observed, regardless of age (1.469 vs. 0.132; p < 0.005). Significant positive correlations were observed between the ADAM10 and ADAM17 RQ, and between the ADAM10 and ADAM28 RQ, in both tumor and marginal tissues (all adjusted p < 0.01). No significant correlations were found between gene expression and corresponding protein levels for ADAM10, ADAM12, or ADAM17. ADAM10, 12, 17, and 28 are poor biomarkers for colorectal cancer, but their significance may increase in patients with comorbid metabolic disorders. The lack of correlation between protein expression and gene expression suggests the contribution of post-transcriptional and post-translational regulatory mechanisms, which justifies further research.

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and its molecular pathogenesis is not fully understood. This exploratory study investigated the expression of three selected microRNAs in colorectal cancer and their associations with previously characterized ADAM transcripts. RT-qPCR was used to assess miR-125b-5p, miR-338-3p, and miR-30c-5p in paired tumor and histologically tumor-free surgical margin tissues from 67 patients. Previously obtained ADAM10, ADAM12, ADAM17, and ADAM28 transcript data from the same cohort were included in correlation analyses. The Wilcoxon signed-rank test and Spearman’s rank correlation were applied, with Benjamini–Hochberg adjustment for multiple testing. MiR-125b-5p expression was lower in tumors than in matched margins (median 0.46 versus 1.33; adjusted p = 0.035). No significant paired differences were identified for miR-338-3p or miR-30c-5p. Margin miR-125b-5p expression was associated with neoadjuvant-treatment history (adjusted p = 0.033), although the treated subgroup was small. No miRNA-ADAM transcript correlations remained significant after adjustment. Positive correlations among some miRNA pairs were observed within tumor and margin tissues. The reduced level of relative miR-125b-5p expression in colorectal cancers is an observational finding consistent with the tumor-suppressor functions described in the literature, but it does not constitute proof of those functions. Inter-miRNA correlations do not demonstrate shared regulatory mechanisms, and the absence of miRNA-ADAM transcript associations does not exclude post-transcriptional regulation.