Tohoku J. Exp. Med., 2021 May, 254(1)

Cul4b Promotes Progression of Malignant Cutaneous Melanoma Patients by Regulating CDKN2A

Chao Zhang,1 Can Cao,1 Xiu-li Liu,2 Tan Jun3 and Pei Liu4

1Department of Dermatology, The Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, China
2Department of Neonatal, Gaotang People's Hospital, Liaocheng, Shandong, China
3Department of Dermatology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, China
4Department of Burn and Plastic Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China

Although several molecular targeted therapy and immunotherapy have been developed, cutaneous melanoma prognosis is still not satisfying. Cul4b promotes the progression of several malignant tumors by regulating cell proliferation. However, its prognostic role in malignant cutaneous melanoma has not been evaluated. In this study, immunohistochemistry was performed to assess the expression of Cul4b in a consecutive patient cohort. The prognostic role of Cul4b was estimated with univariate and multivariate analysis. Cul4b was knocked down in melanoma cell line to evaluate its role in promoting cell proliferation. The results revealed that Cul4b was highly expressed in some of the cutaneous malignant melanoma patients and high expression of Cul4b was associated with poor melanoma-specific overall survival and poor disease-free survival. Cul4b expression was associated with Breslow categories, Clark level, and Ki67 expression. Univariate and multivariate analysis revealed that Cul4b is an independent prognosis risk factor of cutaneous melanoma. Downregulation of Cul4b inhibited the proliferation ability of melanoma cells and downregulated the expression of CDKN2A. These results suggest that Cul4b plays an essential role in cutaneous melanoma progression and may serve as a promising treatment target.

Key words —— CDKN2A; Cul4b; cutaneous melanoma; proliferation

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Tohoku J. Exp. Med 2021, 254, 33-39.

Correspondence: Pei Liu, Department of Burn and Plastic Surgery, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, Shandong 250012, China.

e-mail: liupei_peiliu@126.com