miR­26a inhibits ovarian cancer cell proliferation, migration and invasion by targeting TCF12.

Epithelial ovarian cancer (OC) is a common cause of death from gynecological tumors. MicroRNAs (miRNAs) may function as either oncogenes or tumor suppressors, playing crucial role not only in tumorigenesis, but also in tumor invasion and metastasis. miR­26a and transcription factor 12 (TCF12) have been reported to be involved in carcinogenesis, but the regulatory role of miR­26a/TCF12 in OC remains unknown. The aim of the present study was to investigate the expression profiles of TCF12 and miR­26a in OC patients and the correlation between TCF12 and miR­26a expression, and to demonstrate the effects of miR­26a binding on TCF12, to further reveal the miR­26a/TCF12 regulatory effects on the proliferation, migration, invasion and apoptosis in OC cells. In the present study, the expression of miR­26a was found to be low, while TCF12 was highly expressed in OC patient tissues and cell lines, and low miR­26a expression was statistically significantly correlated with high TCF12 expression. To the best of our knowledge, the present study was the first to demonstrate that TCF12 is a direct target of miR­26a, and upregulation of miR­26a resulted in TCF12 inhibition in OC cells. Furthermore, the proliferation, migration and invasion were inhibited and apoptosis was induced by miR­26a upregulation in OC cells. These results indicated that miR­26a may act as a tumor suppressor in OC, and TCF12 targeting by miR­26a may be a new therapeutic strategy for OC.

Gene expression profiling of the Notch-AhR-IL22 axis at homeostasis and in response to tissue injury.

Notch and interleukin-22 (IL-22) signaling are known to regulate tissue homeostasis and respond to injury in humans and mice, and the induction of endogenous aryl hydrocarbon receptor (Ahr) ligands through Notch links the two pathways in a hierarchical fashion. However in adults, the species-, organ- and injury-specific gene expression of the Notch-AhR-IL22 axis components is unknown. We therefore performed gene expression profiling of DLL1, DLL3, DLL4, DLK1, DLK2, JAG1, JAG2, Notch1, Notch2, Notch3, Notch4, ADAM17/TNF-α ADAM metalloprotease converting enzyme (TACE), PSEN1, basigin (BSG)/CD147, RBP-J, HES1, HES5, HEY1, HEYL, AHR, ARNT, ARNT2, CYP1A1, CYP24A1, IL-22, IL22RA1, IL22RA2, IL10RB, and STAT3 under homeostatic conditions in ten mature murine and human organs. Additionally, the expression of these genes was assessed in murine models of acute sterile inflammation and progressive fibrosis. We show that there are organ-specific gene expression profiles of the Notch-AhR-IL22 axis in humans and mice. Although there is an overall interspecies congruency, specific differences between human and murine expression signatures do exist. In murine tissues with AHR/ARNT expression CYP1A1 and IL-22 were correlated with HES5 and HEYL expression, while in human tissues no such correlation was found. Notch and AhR signaling are involved in renal inflammation and fibrosis with specific gene expression changes in each model. Despite the presence of all Notch pathway molecules in the kidney and a model-specific induction of Notch ligands, IL-22 was only up-regulated in acute inflammation, but rapidly down-regulated during regeneration. This implies that for targeting injury responses, e.g. via IL-22, species-specific differences, injury type and time points have to be considered.