RESUMO
ABSTRACT PreS/S gene mutations could impact virus secretion, infection and immune evasion. However, the relationship between PreS/S mutations and intrauterine transmission has not yet been clarified. Thus, we aimed to explore the associations between PreS/S gene mutations of HBV isolated from mothers and intrauterine transmission. We analyzed the mutations of PreS/S regions of the HBV genome in mothers with HBV DNA levels ≥ 106 IU/mL whose neonates experienced HBV intrauterine transmission (transmission group, GT) and those whose neonates did not experience intrauterine transmission (control group, GC) analyzed using clone-based sequencing. In total, 206 sequences were successfully amplified, including 98 sequences (from 21 mothers) from GT and 108 sequences (from 20 mothers) from GC of genotype C for mutational analysis. Among the 1203 nucleotides of PreS/S regions, there were 219 (18.20%) base substitutions, of which 103 (47.03%) base mutations caused amino acid changes. F80S, A90V and I68T were mutation hotspots. Mothers in GT had a higher mutation rate of A90V in the PreS1 gene than mothers in GC. The A90V mutation increased the risk of HBV intrauterine transmission after adjusting the maternal age and the mode of delivery (OR = 6.23, 95% CI: 1.18-32.97). Moreover, the area under the ROC curve (AUC) for intrauterine transmission due to A90V and a combination of A90V with the mode of delivery were 0.723 (95% CI: 0.575 to 0.891, P = 0.011) and 0.848 (95% CI: 0.723 to 0.972, P < 0.001), respectively. Mothers with the A90V mutation in the PreS1 gene may be a potential risk factor for HBV intrauterine transmission.
RESUMO
The objective of this study was to investigate the effect of human esophageal fibroblast-derived exosomal miR-21 on cisplatin sensitivity against esophageal squamous EC9706 cells. EC9706 cells were co-cultured indirectly with human esophageal fibroblasts (HEF) or miR-21 mimics transfected-HEF in the transwell system. The exosomes in HEF-culture conditioned medium were extracted by differential ultracentrifugation. EC9706 cells were co-cultured with HEF-derived exosomes directly. The cisplatin sensitivity against EC9706 cells was revealed via half maximal inhibitory concentration (IC50) values using MTT assay. The expressions of miR-21, programmed cell death 4 (PDCD4) mRNA, and gene of phosphate and tension homology deleted on chromosome ten (PTEN) mRNA were determined by qRT-PCR. The changes of the protein level were detected using western blot assay. IC50 values of cisplatin against EC9706 cells were increased after EC9706 cells were co-cultured with either HEF or exosomes derived from miR-21 mimics-transfected HEF. Following the increased level of miR-21, the mRNA expression and protein levels of PTEN and PDCD4 were decreased in EC9706 cells. The cisplatin sensitivity to EC9706 cells was reduced by HEF-derived exosomal miR-21 through targeting PTEN and PDCD4. This study suggested that non-tumor cells in the tumor micro-environment increased the tumor anti-chemotherapy effects through their exosomes.