Silencing endothelin-3 expression attenuates the malignant behaviors of human melanoma cells by regulating SPARC levels.
10.1007/s11596-013-1162-3
- Author:
Xiang-jie AN
1
,
2
;
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
Author Information
1. Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China, anxiangjie@
2. com.
- Publication Type:Journal Article
- MeSH:
Cell Line, Tumor;
Endothelin-3;
genetics;
Gene Silencing;
Humans;
Melanoma;
genetics;
pathology;
Osteonectin;
genetics
- From:
Journal of Huazhong University of Science and Technology (Medical Sciences)
2013;33(4):581-586
- CountryChina
- Language:English
-
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.
