Silencing Wnt2B by siRNA Interference Inhibits Metastasis and Enhances Chemotherapy Sensitivity in Ovarian Cancer

Wang, Hongyan; Fan, Liangsheng; Xia, Xi; Rao, Yumei; Ma, Qing; Yang, Jie; Lu, Yao; Wang, Changyu; Ma, Ding; Huang, Xiaoyuan

doi:10.1097/igc.0b013e3182540284

Cited by 27 publications

(18 citation statements)

References 27 publications

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“…Furthermore, WNT2B can upregulate the expression of cyclin D1 and β-catenin, and increases the chemoresistance of oral cancer cells to cisplatin (30). Additionally, silencing WNT2B can inhibit the metastasis of ovarian cancer cells through epithelial-mesenchymal transition (EMT) and the Akt serine/threonine kinase signalling pathway in vitro (31). These findings illustrate that Wnt2B serves an important role in tumour malignancy.…”

Section: Discussionmentioning

confidence: 99%

miR-185-3p regulates the invasion and metastasis of nasopharyngeal carcinoma by targeting WNT2B in vitro

et al. 2017

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MicroRNAs (miRs) have been recognised as important regulators of malignant behaviour in different types of human cancer, including nasopharyngeal carcinoma (NPC). A previous study by our group revealed that miR-185-3p regulates the radioresistance of NPC cells. The present study aimed to investigate the effect of miR-185-3p on NPC invasion and metastasis. Human NPC CNE-2 and 5-8F cell lines were transfected with a miR-185-3p mimic and miR-185-3p inhibitor, respectively, and their effects on the invasion and metastasis of these cells was assessed using a wound healing assay and Matrigel invasion assay. The target gene of miR-185-3p, Wnt family member 2B (WNT2B) was silenced in 5-8F cells using siRNA in order to investigate its function in NPC. Data from the present study demonstrated that the expression of miR-185-3p was the highest in 5-8F and lowest in CNE-2 cells out of a range of NPC cell lines. Following the transfection of miR-185-3p mimic into CNE-2 cells, the wound healing and Matrigel invasion assays indicated that the migration and invasion ability of CNE-2 cells was significantly reduced compared with the negative control group. In addition, the inhibition of miR-185-3p in 5-8F cells significantly increased the capacity for migration and invasion. Furthermore, silencing WNT2B expression resulted in a significant reduction in the invasion and metastasis in 5-8F cells. The inhibition of miR-185-3p, which promotes invasion and metastasis, could be reversed through the silencing of WNT2B in 5-8F cells. The results of the present study indicate that miR-185-3p mediates the invasion and metastasis of NPC by targeting WNT2B in vitro.

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Section: Discussionmentioning

confidence: 99%

miR-185-3p regulates the invasion and metastasis of nasopharyngeal carcinoma by targeting WNT2B in vitro

et al. 2017

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“…Kobayashi et al demonstrate that Wnt2b plays a positive role in the proliferation of mesothelioma[28]. Similarly, Wang et al report that silencing Wnt2b significantly diminishes proliferation in several ovarian cancer cell lines[29]. In addition, Shojima et al report that Wnt5a is capable of promoting proliferation in a variety of oncological cell lines; knockout of Wnt5a reduces proliferation[30].…”

Section: Discussionmentioning

confidence: 99%

A crosstalk between TGF-β/Smad3 and Wnt/β-catenin pathways promotes vascular smooth muscle cell proliferation

DiRenzo

Chaudhary

Shi

et al. 2016

Cellular Signalling

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Rationale Endovascular interventions performed for atherosclerotic lesions trigger excessive vascular smooth muscle cell (SMC) proliferation leading to intimal hyperplasia. Our previous studies show that following endovascular injury, elevated TGF-β/Smad3 promotes SMC proliferation and intimal hyperplasia. Furthermore in cultured SMCs, elevated TGF-β/Smad3 increases the expression of several Wnt genes. Here we investigate a crosstalk between TGF-β/Smad3 and Wnt/β-catenin signaling and its role in SMC proliferation. Methods and Results To mimic TGF-β/Smad3 up-regulation in vivo, rat aortic SMCs were treated with Smad3-expressing adenovirus (AdSmad3) or AdGFP control followed by stimulation with TGF-β1 (or solvent). AdSmad3/TGF-β treatment up-regulated Wnt2b, Wnt4, Wnt5a, Wnt9a, and Wnt11 (confirmed by qRT-PCR and ELISA), and also increased β-catenin protein as detected by Western blotting. Blocking Wnt signaling using a Frizzled receptor inhibitor (Niclosamide) abolished TGF-β/Smad3-induced β-catenin stabilization. Increasing β-catenin through degradation inhibition (using SKL2001) or by adenoviral expression enhanced SMC proliferation. Furthermore, application of recombinant Wnt2b, Wnt4, Wnt5a, or Wnt9a, but not Wnt11, stabilized β-catenin and stimulated SMC proliferation as well. In addition, increased β-catenin was found in the neointima of injured rat carotid artery where TGF-β and Smad3 are known to be up-regulated. Conclusions These results suggest a novel mechanism whereby elevated TGF-β/Smad3 stimulates the secretion of canonical Wnts which in turn enhances SMC proliferation through β-catenin stabilization. This crosstalk between TGF-β/Smad3 and Wnt/β-catenin canonical pathways provides new insights into the pathophysiology of vascular SMCs linked to intimal hyperplasia.

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“…Similar restoration of chemosensitivity has also been demonstrated by targeting the Hedgehog pathway with clinically available Smoothened inhibitors (44), and is effective in reducing spheroid-forming capacity of cells in differentiating-inhibiting media (45). The Wnt pathway contributes to platinum resistance and can also be used to sensitize cells to platinum agents, either by downregulation of individual components of the pathway such as Wnt2B (46) or by using the c-kit inhibitor imatinib, which blocks Wnt signaling (47). Indeed many targeted therapies that failed as single agents may have more efficacy if used in combination with chemotherapy, as chemoresistance pathways are reduced.…”

Section: Targeting Cancer Stem Cellsmentioning

confidence: 99%

Ovarian cancer stem cells: Are they real and why are they important?

Shah

Landen

2014

Gynecologic Oncology

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The cancer stem cell hypothesis has been put forward as a paradigm to describe varying levels of aggressiveness in heterogeneous tumors. Specifically, many subpopulations have been clearly demonstrated to possess increased tumorigenicity in mice, broad differentiating capacity, and resistance to therapy. However, it is still not clear the extent to which these experimental findings are potentially clinically significant. This review will describe the principles of this emerging hypothesis, ways in which it may be appropriate in ovarian cancer based on the clinical course of the disease, and how we might exploit it to improve outcomes in ovarian cancer patients.

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Silencing Wnt2B by siRNA Interference Inhibits Metastasis and Enhances Chemotherapy Sensitivity in Ovarian Cancer

Abstract: These data suggest that Wnt2B indeed plays an important role in ovarian cancer metastasis and drug resistance. This study may provide a new therapeutic target for and a better understanding of ovarian cancer therapy.

Cited by 27 publications

References 27 publications

miR-185-3p regulates the invasion and metastasis of nasopharyngeal carcinoma by targeting WNT2B in vitro

miR-185-3p regulates the invasion and metastasis of nasopharyngeal carcinoma by targeting WNT2B in vitro

A crosstalk between TGF-β/Smad3 and Wnt/β-catenin pathways promotes vascular smooth muscle cell proliferation

Ovarian cancer stem cells: Are they real and why are they important?

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