Oncotarget

Research Papers:

Regulator of G protein signaling 4 inhibits human melanoma cells proliferation and invasion through the PI3K/AKT signaling pathway

Xiaotong Xue, Lihua Wang, Xianguang Meng, Jing Jiao and Ningning Dang _

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Oncotarget. 2017; 8:78530-78544. https://doi.org/10.18632/oncotarget.20825

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Abstract

Xiaotong Xue1,2, Lihua Wang2, Xianguang Meng2, Jing Jiao3 and Ningning Dang2,4

1School of Medicine, Shandong University, Jinan, Shandong Province, China

2Department of Dermatology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong Province, China

3Department of Dermatology, The Chinese People’s Liberation Army 88 Hospital, Taian, Shandong Province, China

4College of Life Science, Shandong Normal University, Jinan, Shandong Province, China

Correspondence to:

Ningning Dang, email: ningningdangxj@sina.com

Keywords: RGS4, melanoma, proliferation, invasion, PI3K/Akt

Received: May 16, 2017     Accepted: August 26, 2017     Published: September 11, 2017

ABSTRACT

Melanoma is a tumor produced by skin melanocytes, which has a high metastatic rate and poor prognosis. So far, plenty of work has been done on melanoma, but mechanisms underlying melanoma development have not been fully elucidated. Here we identified regulator of G protein signaling 4(RGS4) as novel therapeutic target for malignant melanoma and its regulating effect on melanoma. We found that endogenous RGS4 expression was much lower in melanoma tissues and cells. In A375 cell line with low endogenous RGS4 expression, the function of RGS4 was detected by up-regulation its expression with pcDNA3.1-RGS4 and knockdown its expression with siRNA. Our results showed that RGS4 could significantly reduce the proliferation, migration and invasion of melanoma cells. RGS4 is an important regulator for the apoptosis of melanocyte, and the apoptosis rate is significantly decreased in low RGS4 enviroment. RGS4 induced non-activation of PI3K/AKT pathway, resulting in decreased expression of E2F1 and Cyclin D1, thus constraining cell proliferation and invasion. These results were further confirmed in M14 cell lines. Collectively, our findings show that RGS4 plays an important role in multiple cellular functions of melanoma development and is valuable to be a therapeutic target.


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