J Cancer 2022; 13(6):1958-1971. doi:10.7150/jca.69497 This issue

Research Paper

Suppression of CCT3 inhibits melanoma cell proliferation by downregulating CDK1 expression

Wenlou Liu1*, Xiuli Zhang2*, Cheng Chen3, Yizhi Li4, Chunsheng Yang5, Zhengxiang Han1, Guan Jiang3✉, Yanqun Liu3✉

1. Department of Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
2. Department of Radiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
3. Department of Dermatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
4. Department of Dermatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, China.
5. Department of Dermatology, Affiliated Huai'an Hospital of Xuzhou Medical University, the Second People's Hospital of Huai'an, Huai'an 223002, China.
*Wenlou Liu and Xiuli Zhang contributed equally to this work.

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Citation:
Liu W, Zhang X, Chen C, Li Y, Yang C, Han Z, Jiang G, Liu Y. Suppression of CCT3 inhibits melanoma cell proliferation by downregulating CDK1 expression. J Cancer 2022; 13(6):1958-1971. doi:10.7150/jca.69497. Available from https://www.jcancer.org/v13p1958.htm

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Abstract

Graphic abstract

The eukaryotic chaperonin family is vital for cell survival. The dysregulation of chaperonin-containing TCP-1 subunit 3 (CCT3) is implicated in several types of malignant tumors' development. However, its functional role in melanoma remains unknown. Here we elucidate the functional contribution to CCT3 to melanoma progression. The results indicated that CCT3 highly expressed in melanoma tissues, and CCT3 overexpression is correlated with clinical stage in melanoma patients. Knockdown of CCT3 by shRNA in melanoma cells inhibited cell proliferation and cell cycle progression and induced cell apoptosis in vitro. In vivo, tumor growth in the nude mice was significantly inhibited after CCT3 silencing. Importantly, the gene array analysis showed that CCT3 depletions inhibited cyclins and cell cycle regulation signaling and further evaluation demonstrated that CDK1 expression was significantly decreased after CCT3 knockdown. Additionally, Functional rescues experiments also indicated that decreased cell proliferation due to CCT3 silencing was rescued by CDK1 overexpression. Overall, our findings suggest that CCT3 depletions prohibited melanoma progression by downregulating CDK1 expression and is a potential therapeutic target for melanoma.

Keywords: melanoma, chaperonin containing TCP1, subunit 3, proliferation, apoptosis