title: Silencing endothelin-3 expression attenuates the malignant behaviors of human melanoma cells by regulating SPARC levels.
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.
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Xiang-Jie
authors.initials: XJ
authors.lastname: An
authors.affiliation: Department of Dermatology, Zhongshan Hospital, Wuhan, 430033, China.
authors.forename: Yan-Qiu
authors.initials: YQ
authors.lastname: Li
authors.affiliation: Department of Dermatology, No.457 Airforce Hospital, Wuhan, 430012, China.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Qu
authors.affiliation: Department of Dermatology, Wuhan General Hospital of Guangzhou Command, Wuhan, 430070, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Si-Yuan
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Hong-Xiang
authors.initials: HX
authors.lastname: Chen
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Tu
authors.affiliation: Department of Dermatology and Skin Science, University of British Columbia, Vancouver, V5Z 4E8, Canada. ywzhou@interchange.ubc.ca.
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Zhou
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. hcz0501@126.com.
authors.forename: Chang-Zheng
authors.initials: CZ
authors.lastname: Huang
mesh_terms: D045744:Cell Line, Tumor; D019334:Endothelin-3 / Q000235:genetics*; D020868:Gene Silencing; D006801:Humans; D008545:Melanoma / Q000235:genetics* / Q000473:pathology*; D015676:Osteonectin / Q000235:genetics*
chemical_list: D019334:Endothelin-3; D015676:Osteonectin; C577241:SPARC protein, human
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