Overexpression of HOTAIR (HOX antisense intergenic RNA) is significantly correlated with tumor progression and poor prognosis in human ovarian cancer. However, the underlying mechanisms are largely unknown. In the present study, we investigated the roles of HOTAIR in the initiation and chemoresistance of ovarian cancer. As our data show, HOTAIR overexpression promoted cell cycle progression (and thus cell proliferation) by activating the wnt/β-catenin signaling pathway. Likewise, knockdown of HOTAIR suppressed cell proliferation and arrested cell cycle at G1 phase via inhibition of wnt/β-catenin signaling. Moreover, the results of primary culture demonstrated that elevated HOTAIR expression correlated positively with chemoresistance in ovarian cancer. In vitro and in vivo, HOTAIR induced cellular resistance to cisplatin by activating the wnt/β-catenin pathway, which could be reversed by pre-treatment with the wnt/β-catenin inhibitor, XAV939. In conclusion, HOTAIR promotes the initiation and chemoresistance of ovarian cancer by activating wnt/β-catenin signaling, suggesting that HOTAIR might be a potent therapeutic target for ovarian cancer treatment.

Although accumulating evidence indicates that both β-catenin and osterix (Osx) are essential for bone and tooth development, few studies have investigated the interaction of these two key proteins in the context of cementogenesis. In this study, we used transgenic mice with constitutively active β-catenin and inactive Osx in the dental mesenchyme to address this question. We found that cementoblasts with constitutively active β-catenin require Osx to produce excessive cellular cementum, and that ablation of Osx prevents this abnormal accumulation. Importantly, cementoblasts transduced with retrovirus expressing constitutively active β-catenin exhibited upregulation of Osx expression through direct binding to the promoter region of Osx. Osx regulates Lef1 expression and consequently could regulate T-cell factor/lymphoid enhancer factor (Tcf/Lef) binding activity in Wnt/β-catenin signaling. However, the loss of Tcf/Lef binding activity by Osx ablation was not rescued by transduction of retrovirus expressing constitutively active β-catenin or ectopic Lef1 overexpression. These results suggest that the Tcf/Lef binding activity of Wnt/β-catenin signaling is Osx-dependent during cementogenesis. Moreover, Osx differentially regulates the expression of various Tcf family members, suggesting that Osx regulates cementogenesis by utilizing various Tcf/Lef-dependent mechanisms. This is the first report to show that downstream Osx signaling through Tcf/Lefs is critical for cementogenesis.

β‐catenin, a key mediator of Wnt signaling, plays multiple roles in tooth development. However, the role of β‐catenin in Hertwig's epithelial root sheath (HERS) during root formation remains unclear. In this study, we generated inducible tissue‐specific β‐catenin conditional knockout mice (Ctnnb1i∆shh) to investigate how β‐catenin in HERS affects tooth root development. The inactivation of β‐catenin in HERS led to interrupted root elongation due to premature disruption of HERS. This phenotype was accompanied by reduced cell‐cell adhesion and decreased expression of junctional proteins, as well as increased epithelial‐to‐mesenchymal transition of HERS cells upon β‐catenin depletion. Accordingly, stabilization of β‐catenin in HERS (Catnbi∆shh) led to the formation of unfragmented HERS and resulted in the failure of HERS dissociation, with increased expression of junctional proteins. Our results suggest that fine control of β‐catenin is important for HERS to guide root formation through regulating its structural integrity.

Hysteroscopic excision is feasible for patients with symptomatic adenomyosisis.