Down-regulation of miRNA-148a and miRNA-625-3p in colorectal cancer is associated with tumor budding

Abstract

BackgroundMiRNAs are often deregulated in colorectal cancer and might function as tumor suppressors or as oncogenes. They participate in controlling key signaling pathways involved in proliferation, invasion and apoptosis and may serve as prognostic and predictive markers. In this study we aimed to evaluate the role of miRNA-148a and miRNA-625-3p in metastatic colorectal cancer.MethodsFifty-four patients with a first-time diagnosed CRC receiving FOLFOX ± Bevacizumab were involved in the study. Tumor samples underwent routine pathology examination including evaluation for tumor budding and KRAS. MiRNA-148a and miRNA-625-3p expression analysis was done by RT-PCR. Associations between expression of both miRNAs and clinico-pathological factors, treatment outcomes and survival were analyzed.ResultsBoth miRNA-148a and miRNA-625-3p were down-regulated in the tumors compared to normal colonic mucosa. Significantly lower expression of both miRNAs was noticed in tumors with budding phenomenon compared to tumors without it (median values of miRNA-148a were 0.314 and 0.753 respectively, p = 0.011, and 0.404 and 0.620 respectively for miRNA-625-3p, p = 0.036). Significantly lower expression of miRNA-625-3p was detected in rectal tumors, compared to tumors in the colon (median 0.390 and 0.665 respectively, p = 0.037). Progression free survival was significantly lower in patients with high miRNA-148a expression (6 and 9 months respectively, p = 0.033), but there were no significant differences in PFS for miRNA-625-3p and in overall survival for both miRNAs.ConclusionsThere was a significant relationship between low miRNA-148a and miRNA-625-3p expression and tumor budding, which is thought to represent epithelial-mesenchymal transition. Both studied miRNAs may be associated with a more aggressive phenotype and could be the potential prognostic and predictive biomarkers in CRC. Further investigation is needed to confirm miRNAs involvement in EMT, and their prognostic and predictive value.Electronic supplementary materialThe online version of this article (10.1186/s12885-017-3575-z) contains supplementary material, which is available to authorized users.

Exosomes of pasteurized milk: potential pathogens of Western diseases

“…The protein content and size of bovine milk exosomes was significantly reduced in fermented cow's milk associated with a substantial loss of miRs (miR-29b, miR-21) compared to unfermented raw milk [48]. Malignant epithelial cells of CRC exhibit a reduced Melnik and Schmitz J Transl Med (2019) 17:3 expression of miR-148a [267][268][269][270], which increases the expression of DNMT1 that functions as a tumor promoter in CRC [271][272][273]. Intriguingly, Golan-Gerstl et al [44] demonstrated that the incubation of CRC cells (Lim 1215) with human breastmilk exosomes increased the cellular content of miR-148a.…”

Identification of Prognostic Biomarkers and Correlation with Immune Infiltrates in Hepatocellular Carcinoma Based on a Competing Endogenous RNA Network

“…Baolei et al revealed that miRNA-124 is a negative regulator of HCC with respect to proliferation and invasion by downregulating lncRNA-UCA1 [35]. Baltruskeviciene E et al found that downregulated expression of miRNA-148a and miRNA-625-3p is related to tumor budding in colorectal cancer, and EMT was considered a possible molecular mechanism [36].…”

MicroRNA: Another Pharmacological Avenue for Colorectal Cancer?

“…Tumor progression, the final phase of carcinogenesis, is characterized by increased invasiveness and growth ( Jiang et al, 2018 ; Shi et al, 2018 ). Downregulation of miR-148a and miR-625-3p is associated with tumor budding in tumor specimens from 54 patients with a first-time diagnosed colorectal cancer, determined by real-time quantitative (qRT)-PCR ( Baltruskeviciene et al, 2017 ).…”