Human TGFB3 peptide

Our previous results indicated a moderate association between the methylenetetrahydrofolate reductase (MTHFR) gene 677C-T variant and an increased risk of non-syndromic cleft lip with or without cleft palate (nsCL/P) among the northern but not southern population in China, suggesting possible genetic heterogeneity in the etiology of nsCL/P between these two populations. It remains unknown whether the transforming growth factor alpha (TGFA) gene TaqI polymorphism and transforming growth factor beta 3 (TGFB3) gene CA repeats influence the risk of nsCL/P differently between the northern and southern Chinese populations. In this study of 188 Chinese case-parent triads, we found an independent association between the TGFB3 variant and risk of nsCL/P (OR = 2.10, 95% CI: 1.25-3.54 for heterozygotes; OR = 1.78, 95% CI: 0.83-3.83 for homozygotes). The MTHFR variant was associated with an increased risk of nsCL/P among children in the north (OR= 3.11, 95% CI: 1.18-8.23 for heterozygotes; OR = 3.36, 95%CI: 1.14-9.93 for homozygotes) and appear to interact marginally with the TGFB3 variant in the occurrence of nsCL/P among southern subjects (OR = 0.26, 95% CI: 0.06-1.07). No association was found between the TGFA variant and risk of nsCL/P in our data. Our results suggest that the TGFB3 gene variant may be an important genetic risk factor for nsCL/P occurrence in Chinese children, and we found no evidence of heterogeneity between northern and southern Chinese populations in the associations between TGFB3 and TGFA variants and risk of nsCL/P, but these results warrant further investigation. (C) 2010 Wiley-Liss, Inc.

Background Cancer-associated fibroblasts (CAFs) have been intensively studied in recent studies with aims of finding more concrete evidence on their mechanism of involvement in tumor progression, which is currently unknown. CAFs can secrete exosomes which are loaded with proteins, lipids and RNAs, all of which affect tumor microenvironment. The present study identified microRNA-93-5p (miR-93-5p) as a novel exosomal cargo responsible for the pro-tumorigenic effects of CAFs on colorectal cancer (CRC). Methods CAFs and normal fibroblasts (NFs) were isolated from cancerous tissues and matched with paracancerous tissues that had been surgically resected from CRC patients. The interaction among miR-93-5p, forkhead box A1 (FOXA1) and TGFB3 was identified through ChIP and dual luciferase reporter assays. The proliferation and apoptosis of SW480 cells co-cultured with CAFs-derived exosomes under irradiation were evaluated by CCK-8, colony formation, and flow cytometric assays. Tumorigenesis of SW480 cells in nude mice was assessed under the irradiation. Results FOXA1 was found to be associated with reduced radioresistance in CRC cells and was verified as a target of miR-93-5p. CAFs-derived exosomes contained higher miR-93-5p than those from NFs, which augmented SW480 cell proliferation and rescued them from radiation-induced apoptosis. miR-93-5p was identified as a mediator of the exosomal effects of CAFs on SW480 cells, possibly through downregulating FOXA1 and upregulating TGFB3. FOXA1 could bind to the promoter of TGFB3, thereby inhibiting nuclear accumulation of TGFB3. Also, CAFs-derived exosomes containing miR-93-5p increased the tumor growth of SW480 cells in irradiated nude mice. Conclusion The present study identifies miR-93-5p as a specific exosomal cargo that rescues CRC cells against radiation-induced apoptosis.