UCHL3 plays an important role in the occurrence and development of melanoma

Abstract

It has been reported that ubiquitin C-terminal hydrolase-L3 (UCHL3) plays an important role in cancer development; however, the role of UCHL3 in melanoma remains unclear. The present study aimed to investigate the role of ubiquitin C-terminal hydrolase-L3 (UCHL3) and determine its underlying molecular mechanisms in melanoma occurrence and development using in vitro studies. Reverse transcription-quantitative PCR analysis was performed to detect UCHL3 mRNA expression. The MTT assay was performed to assess cell proliferation. Cell apoptosis was analyzed via flow cytometry and the TUNEL assay. Cell ultrastructure was observed via transmission electron microscopy. LC3B protein expression was detected via cellular immunofluorescence, while neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) and LC3 protein expression levels, and NEDD8 ubiquitination were detected via western blot analysis. The results demonstrated that transfection with small interfering (si)RNA-UCHL3 significantly suppressed cell proliferation, whereas apoptosis was significantly enhanced, as well as autophagy, autophagosome formation and LC3B protein expression. In addition, NEDD8 protein expression and autophagosome numbers significantly decreased, while the LC3II/LC3I ratio significantly increased. NEDD8 knockdown via transfection with si-NEDD8 had similar effects to si-UCHL3, as well as si-UCHL3+ si-NEDD8. Taken together, the results of the present study suggest that UCHL3 knockdown decreases melanoma cell proliferation by increasing cell autophagy through regulating NEDD8 expression and autophagosome numbers.

LINC01063 functions as an oncogene in melanoma through regulation of miR-5194-mediated SOX12 expression

“…Terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeling (TUNEL) assay was implemented using the In Situ Cell Death Detection Kit (Roche, Basel, Switzerland) following the supplier's instructions [29]. Cells treated with TUNEL were dyed with 4′,6-diamidino-2-phenylindole (DAPI) and then detected with fluorescence microscopy.…”

UCHL3 promotes hepatocellular carcinoma cell migration by de-ubiquitinating and stabilizing Vimentin

“…UCHL3 exerts an anti-tumor activity to inhibit the epithelial-mesenchymal transition (EMT) and reduce the stem-cell-like properties of prostate cancer cells ( 15 , 16 ). However, oncogenic activities have also been reported with UCHL3 being overexpressed in lung cancer ( 17 , 18 ), ovarian cancer ( 19 ), pancreatic cancer ( 20 ), and melanoma ( 21 ). Aryl hydrocarbon receptor (AhR) ( 22 , 23 ), FOXM1 ( 20 ), lymphoid-specific helicase (LSH) ( 17 ), COPS5 ( 24 ), and RAD51 ( 25 ) are de-ubiquitination targets of UCHL3, which indicate the possibility of UCHL3 being a therapeutic target.…”