Overexpression of CDCA8 promotes the malignant progression of cutaneous melanoma and leads to poor prognosis

被引:74
作者
Ci, Chao [1 ]
Tang, Biao [1 ]
Lyu, Dalun [2 ]
Liu, Wenbei [1 ]
Qiang, Di [1 ]
Ji, Xiang [1 ]
Qiu, Xiamin [1 ]
Chen, Lei [2 ]
Ding, Wei [2 ]
机构
[1] Wannan Med Coll, Affiliated Hosp 1, Dept Dermatol, Wuhu 241001, Anhui, Peoples R China
[2] Wannan Med Coll, Affiliated Hosp 1, Dept Burn & Plast Surg, Wuhu 241001, Anhui, Peoples R China
关键词
cell division cycle associated 8; cutaneous melanoma; prognosis; target gene; proliferation; Rho-associated coiled-coil-containing protein kinase; CANCER; ACTIVATION; EXPRESSION; PATHWAY; RHO; CONTRIBUTES; CARCINOMA; APOPTOSIS; SURVIVAL; INVASION;
D O I
10.3892/ijmm.2018.3985
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Cutaneous melanoma is very aggressive and results in high mortality rates for cancer patients. Determining molecular targets is important for developing novel therapies for cutaneous melanoma. Cell division cycle associated 8 (CDCA8) is a putative oncogene that is upregulated in multiple types of cancer. The present study aimed to examine the role of CDCA8 in cutaneous melanoma, with a focus on the association of its expression to prognosis and metastasis. First, the mRNA expression of CDCA8 in cutaneous melanoma tissues was investigated using the ONCOMINE and Gene Expression Omnibus (GEO) databases. Furthermore, the relationship between the expression of CDCA8 and cutaneous melanoma patient survival was analyzed using a Kaplan-Meier plot and Log Rank test. In addition, the effects of CDCA8 on proliferation, migration and invasion of cutaneous melanoma cell lines were investigated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Cell Counting kit-8, colony formation assay, wound healing and Matrigel assay. Finally, the expression levels of key proteins related to the Rho-associated coiled-coil-containing protein kinase (ROCK) signaling pathway were measured by western blot assay. The results demonstrated that CDCA8 was overexpressed in cutaneous melanoma tissues and cells lines compared with normal tissues, and high expression of CDCA8 was significantly associated with poorer prognosis in patients with cutaneous melanoma. In in vitro experiments, CDCA8 knockdown inhibited A375 and MV3 cell proliferation, migration and invasion. In addition, CDCA8 knockdown reduced the phosphorylation levels of ROCK1 and myosin light chain, two downstream effector proteins of the ROCK pathway. In summary, the present findings suggested that CDCA8 may be a promising therapeutic target for the treatment of cutaneous melanoma.
引用
收藏
页码:404 / 412
页数:9
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