Dataset Information

Upregulation of DACT2 suppresses proliferation and enhances apoptosis of glioma cell via inactivation of YAP signaling pathway.

ABSTRACT: DACT2, one of the Dact gene family members, was shown to function as a tumor suppressor. However, its function in gliomas remains largely unknown. In this study, we investigated the role of DACT2, underlying molecular mechanisms and its clinical significance in glioma patients. Downexpression of DACT2 in gliomas compared with adjacent normal brain tissues was correlated with glioma grade and poor survival. Cox regression analysis revealed that the DACT2 is an independent prognostic indicator for glioma patients. Overexpression of DACT2 in glioma cells inhibited proliferation, cell cycle and enhanced apoptosis, sensitivity to temozolomide in vitro and suppressed tumor growth in vivo. Whereas knockdown of DACT2 induce opposite reaction. Mechanistically, overexpression of DACT2 resulted in upregulation of important signaling molecules such as p-YAP and p-?-catenin, and prevent YAP translocating into nucleus and sequestering in the cytoplasm to degrade. The study further proved that DACT2 can suppress YAP through Wnt/?-catenin signaling pathway. Collectively, these data indicate that DACT2 has a tumor suppressor function via inactivation of YAP pathway, providing a promising target for the treatment of gliomas.

SUBMITTER: Tan Y

PROVIDER: S-EPMC5596571 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Upregulation of DACT2 suppresses proliferation and enhances apoptosis of glioma cell via inactivation of YAP signaling pathway.

Tan Ying Y Li Qiu-Meng QM Huang Ning N Cheng Si S Zhao Guan-Jian GJ Chen Hong H Chen Song S Tang Zhao-Hua ZH Zhang Wen-Qian WQ Huang Qin Q Cheng Yuan Y

Cell death & disease 20170810 8

DACT2, one of the Dact gene family members, was shown to function as a tumor suppressor. However, its function in gliomas remains largely unknown. In this study, we investigated the role of DACT2, underlying molecular mechanisms and its clinical significance in glioma patients. Downexpression of DACT2 in gliomas compared with adjacent normal brain tissues was correlated with glioma grade and poor survival. Cox regression analysis revealed that the DACT2 is an independent prognostic indicator for ...[more]

PMID: 28796248

Similar Datasets

Project description:Renal fibrosis denotes a common complication of diabetic nephropathy and is a predominant cause of end-stage renal disease. Despite the association between microRNAs (miRNAs or miRs) and renal fibrosis, miRNAs have been reported to play a vital role in the development of chronic renal fibrosis. Therefore, the aim of the present study was to investigate the possible function of miR-101a in chronic renal fibrosis. Initially, microarray-based gene expression profiling of renal fibrosis was employed to screen the differentially expressed genes. An in vivo mouse model of chronic renal fibrosis induced by a unilateral ureteral obstruction (UUO) and an in vitro cell model induced by aristolochic acid (AA) were constructed. miR-101a expression was examined using a fluorescence in situ hybridization (FISH) assay and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Then, the interaction between miR-101a and KDM3A was identified using an online website combined with a dual-luciferase reporter assay. Finally, gain- and loss-of-function experiments were conducted to elucidate the effect of miR-101a on the expression of Col1a1, fibronectin, ?-smooth muscle actin (?-SMA), and YAP-TGF-? (transforming growth factor ?)-Smad signaling pathway-related genes, as well as the degree of renal fibrosis. miR-101a was poorly expressed while KDM3A was robustly induced in chronic renal fibrosis tissues and cells. In addition, miR-101a could target and downregulate KDM3A expression, which led to elevated TGIF1, inhibited expression of Collagen I (Col1a1), fibronectin, ?-SMA, YAP1, and TGF-?2 along with the extent of Smad2/3 phosphorylation, as well as delayed renal fibrosis degree. Besides, overexpressed YAP/TGF-?2 or inhibited TGIF1 partially restored the inhibitory effect of miR-101a on chronic renal fibrosis. Taken together, miR-101a could potentially slow down chronic renal fibrosis by the inactivation of the YAP-TGF-?-Smad signaling pathway via KDM3A, highlighting the potential of miR-101a as a therapeutic target for chronic renal fibrosis treatment.

Dataset Information

Upregulation of DACT2 suppresses proliferation and enhances apoptosis of glioma cell via inactivation of YAP signaling pathway.

Publications

Upregulation of DACT2 suppresses proliferation and enhances apoptosis of glioma cell via inactivation of YAP signaling pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets