Silencing endothelin-3 expression attenuates the malignant behaviors of human melanoma cells by regulating SPARC levels.

Xiang-jie An, Yan-qiu Li, Xiao-ying Qu, Jing Zhang, Ling-yun Zhang, Ming Wang, Li Zhu, Si-yuan Chen, Hong-xiang Chen, Ya-ting Tu, Yu-wen Zhou, Chang-zheng Huang

Index: J. Huazhong Univ. Sci. Technolog. Med. Sci. 33(4) , 581-6, (2013)

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Abstract

Endothelin-3 (ET-3) is aberrantly expressed in both metastatic melanoma tissues and cultured melanoma cells. Our previous work showed that ET-3 could promote survival of metastatic melanoma cells via its altered expression. In this study, we investigated the mechanisms responsible for these gene-induced phenotypes in melanoma cells. An ET-3 gene sequence-specific shRNA vector pLVTHM-ET3-RNAi was constructed and transfected into human malignant melanoma cells A375 and MMRU, and the resultant molecular events and cellular changes were examined. As compared with the empty-vector group, cell proliferation was slowed down, and the growth inhibition rates were 38.9% in A375 cells and 38.4% in MMRU cells after transfection. In addition, cell invasion capability was also inhibited, with a reduction of 62.2% in A375 cells and 54.3% in MMRU cells. The percentage of apoptotic cells was found to increase. Meanwhile, in both cell lines, secreted protein acidic and rich in cysteine (SPARC) levels were down-regulated together with inhibition of its upstream signaling molecule, NF-κB. Thus, the current results suggested that down-regulated expression of ET3 attenuates the malignant behaviors of human melanoma cells partially by decreasing the expression of SPARC and NF-κB.