Suppression of CCT3 inhibits melanoma cell proliferation by downregulating CDK1 expression

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.

Integrative analysis of the role of CCT3 in human pan-cancer

“…In the present study, mechanism analysis con rmed that CCT3 was closely linked to cell-cycle related biological processes, such as the biogenesis of ribonucleoprotein complexes, DNA metabolic processes, mitotic cell cycle, G2/M transition and regulation of DNA repair. These results are consistent with previous studies in which W. Liu et al demonstrated that CCT3 silencing in melanoma exerts tumor suppressive effects through the downregulation of cell cycle protein-dependent kinase 1 (CDK1) 29 . In addition, Chen et al found that the knockdown of CCT3 promoted apoptosis and cell cycle arrest in cancer cells in LUAD 30 .…”

Hsa_circ_0079662 induces the resistance mechanism of the chemotherapy drug oxaliplatin through the TNF‐α pathway in human colon cancer

“…About 1 × 10 5 cells were added to 24‐well plates. Using a cotton swab, non‐migrated cells in the upper chamber were removed after migration, and the cotton filters were fixed with 4% paraformaldehyde 29 . Cell number was counted in five random fields of each chamber under a microscope.…”

“…Each sample was separated by 15% SDS‐PAGE, and the membranes were incubated for 12 hours at 4°C with antibodies and then incubated with goat‐anti‐mouse IgG (Santa Cruz Biotechnology). The signals were detected with ECL reagents 29 …”

Calreticulin regulates the expression of MMP14 and ADAR1 through EIF2AK2 signaling to promote the proliferation and progression of malignant melanoma cells

“…For advanced melanoma, many new medications have been developed, such as immunotherapy, gene therapy, and bio-chemotherapy [13,34]. However, the five-year survival rate for melanoma patients is only 10% [35,36]. Furthermore, the absence of clear indications and symptoms in the early stages of melanoma leads to the diagnosis of around 80% of patients only at advanced stages of the illness [36,37].…”