Background:MicroRNAs are noncoding regulatory RNAs strongly implicated in carcinogenesis, cell survival, and chemosensitivity. Here, microRNAs associated with chemoresistance in ovarian carcinoma, the most lethal of gynaecological malignancies, were identified and their functional effects in chemoresistant ovarian cancer cells were assessed.Methods:MicroRNA expression in paclitaxel (PTX)-resistant SKpac sublines was compared with that of the PTX-sensitive, parental SKOV3 ovarian cancer cell line using microarray and qRT–PCR. The function of differentially expressed microRNAs in chemoresistant ovarian cancer was further evaluated by apoptosis, cell proliferation, and migration assays.Results:Upregulation of miR-106a and downregulation of miR-591 were associated with PTX resistance in ovarian cancer cells and human tumour samples. Transfection with anti-miR-106a or pre-miR-591 resensitized PTX-resistant SKpac cells to PTX by enhancing apoptosis (23 and 42% increase), and inhibited their cell migration (43 and 56% decrease) and proliferation (64 and 65% decrease). Furthermore, ZEB1 was identified as a novel target gene of miR-591, and BCL10 and caspase-7 were target genes of miR-106a, as identified by immunoblotting and luciferase assay.Conclusion:MiR-106a and miR-591 have important roles in conferring PTX resistance to ovarian cancer cells. Modulation of these microRNAs resensitizes PTX-resistant cancer cells by targeting BCL10, caspase-7, and ZEB1.
Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are characterized by an increase in hepatic triglyceride content with infiltration of immune cells, which can cause steatohepatitis and hepatic insulin resistance. C-C chemokine receptor 7 (CCR7) is primarily expressed in immune cells, and CCR7 deficiency leads to the development of multi-organ autoimmunity, chronic renal disease and autoimmune diabetes. Here, we investigated the effect of CCR7 on hepatic steatosis in a mouse model and its underlying mechanism. Our results demonstrated that body and liver weights were higher in the CCR7−/− mice than in the wild-type (WT) mice when they were fed a high-fat diet. Further, glucose tolerance and insulin sensitivity were markedly diminished in CCR7−/− mice. The number of invariant natural killer T (iNKT) cells was reduced in the livers of the CCR7−/− mice. Moreover, liver inflammation was detected in obese CCR7−/− mice, which was ameliorated by the adoptive transfer of hepatic mononuclear cells from WT mice, but not through the transfer of hepatic mononuclear cells from CD1d−/− or interleukin-10-deficient (IL-10−/−) mice. Overall, these results suggest that CCR7+ mononuclear cells in the liver could regulate obesity-induced hepatic steatosis via induction of IL-10-expressing iNKT cells.
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