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

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.

Targeting RGS4 Ablates Glioblastoma Proliferation

“…Recent studies conducted on RGS4 have illustrated its role in tumor development and in diverse pathologies, including CNS diseases, cardiovascular disease and diabetes [21,22,36,37]. However, very little information is reported regarding its role in glioblastoma.…”

“…RGS4 s implication in cancer is not well documented, other than as a novel regulator in malignant melanoma [21]. RGS4 has recently been studied as a tumor promoter in glioma cells by acting positively on tumor cell motility, and is reported to be a potent driver of human glioma cell invasiveness [22].…”

Ginsenoside Rb1 attenuates intestinal ischemia/reperfusion‑induced inflammation and oxidative stress via activation of the PI3K/Akt/Nrf2 signaling pathway

“…Phosphoinositide 3-kinase (PI3K), a member of the phospholipid kinase family, serves important roles in the regulation of the apoptosis, proliferation, differentiation and metabolism of cells (9). The serine-threonine protein kinase Akt is a downstream target of PI3K; when stimulated by extracellular signals, PI3K-activated Akt initiates a cascade of intracellular reactions (10).…”

Adenomatous Polyposis Coli Loss Controls Cell Cycle Regulators and Response to Paclitaxel

“…GLI1 is an effector protein of the Hedgehog (Hh) pathway, involved in cell development and differentiation. Increased expression of GLI1 has been shown to be associated with metastasis, increased proliferation, and the enrichment of cancer stem cells [38-40]. Increased transcription of cell proliferation and cell survival genes, such as cyclin D1 and Bcl-2, has been linked to the active Hh pathway [41].…”