Transforming growth factor beta 1 (TGF-beta1) is a pro-fibrotic cytokine with a key role in wound repair and regeneration, including induction of fibroblast-to-myofibroblast transition. Genistein is a naturally occurring selective estrogen receptor modulator with promising anti-fibrotic properties. In the present study we aimed to investigate whether genistein modulates TGF-beta1 (canonical and non-canonical) signaling in normal dermal fibroblasts at the protein level (Western blot and immunofluorescence). We demonstrated that TGF-beta1 induces the myofibroblast-like phenotype in the studied fibroblast signaling via canonical (SMAD) and non-canonical (AKT, ERK1/2, ROCK) pathways. Genistein induced only ERK1/2 expression, whereas the combination of TGF-beta1 and genistein attenuated the ERK1/2 and ROCK signaling. Of note, the other studied pathways remained almost unaffected. From this point of view, genistein does not impair conversion of normal fibroblasts to myofibroblast-like cells.

• MeSH
• Fibroblasts drug effects   metabolism   MeSH
• Phytoestrogens pharmacology   MeSH
• Genistein pharmacology   MeSH
• Humans MeSH
• Drug Evaluation, Preclinical MeSH
• Primary Cell Culture MeSH
• Signal Transduction drug effects   MeSH
• Transforming Growth Factor beta1 antagonists & inhibitors   metabolism   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Phytoestrogens MeSH
• Genistein MeSH
• TGFB1 protein, human MeSH Browser
• Transforming Growth Factor beta1 MeSH

We report that decreased expression of miR-30c in tumor compared to adjacent tissue is sex-dependent in colorectal cancer (CRC) patients. High expression of miR-30c was associated with better survival in the whole cohort. When the cohort was split into male and female subcohorts, decreased miR-30c expression in tumor compared to adjacent tissue was observed only in males. Expression of miR-30c was decreased in CRC tumor tissue in male patients with nodes involvement compared to those without metastases in nodes and this difference was not observe in females. Next dependency of miR-30c expression on oestrogen receptor beta (ERbeta) mRNA levels in tumor was tested. In males with low expression of ERbeta, we observed a significant decrease in miR-30c levels in patients with nodes involvement compared to those without nodes involvement. This difference was not observed in males with high ERbeta mRNA levels and in females. Accordingly, males with low expression of ERbeta and high expression of miR-30c showed a better survival that those with low expression ERbeta and low expression of miR-30c. It is possible to conclude that whole cohort survival dependence on miR-30c is mostly generated by a subcohort of males with low expression of ERbeta mRNA in tumor tissue.

• MeSH
• Estrogen Receptor beta genetics   metabolism   MeSH
• Cohort Studies MeSH
• Colorectal Neoplasms genetics   metabolism   pathology   MeSH
• Humans MeSH
• MicroRNAs biosynthesis   genetics   MeSH
• Survival Rate MeSH
• Biomarkers, Tumor biosynthesis   genetics   MeSH
• Prognosis MeSH
• Aged MeSH
• Sex Factors MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Estrogen Receptor beta MeSH
• MicroRNAs MeSH
• MIRN30a microRNA, human MeSH Browser
• Biomarkers, Tumor MeSH