Proteasome beta-4 subunit contributes to the development of melanoma and is regulated by miR-148b

Abstract

The proteasome beta-4 subunit is required for the assembly of 20S proteasome complex, forming a pivotal component for the ubiquitin-proteasome system. Emerging evidence indicates that proteasome beta-4 subunit may be involved in underlying progression and mechanisms of malignancies. However, the role of proteasome beta-4 subunit in melanoma is currently unknown. Here, we reported that proteasome beta-4 subunit was markedly upregulated in human melanoma tissues and cells, compared with normal skin samples. High proteasome beta-4 subunit levels were significantly associated with poor overall survival in patients with melanoma. Proteasome beta-4 subunit knockdown strongly decreased melanoma cell growth in vitro and in vivo. We further identified miR-148b as a negative regulator of proteasome beta-4 subunit. Enforced expression of miR-148b resulted in vitro growth inhibition of melanoma cells, whereas this inhibition was further abolished by enforced expression of proteasome beta-4 subunit. Our findings, for the first time, indicated that the miR-148b/proteasome beta-4 subunit axis contributed to the development of melanoma, revealing novel therapeutic targets for the treatment of melanoma.

Parvimonas micra infection enhances proliferation, wound healing, and inflammation of a colorectal cancer cell line

“…Of note, up-regulation of PSMB4 was also found in P. micra-HT-29, which hypothetically occurred alongside the increased expression of neighbouring proteasomal subunits of PSMA1, PSMA3, PSMB8, PSMC2, PSMD1, PSMD5 and PSMD6. These protein components are crucial to the ubiquitin-proteasome pathway (UPP) activation in cancer [38,39], where they interfere degradation of β-catenin via Wnt signalling, resulting in continuous proliferation and metastasis in CRC [40,41]. PSMB4 was also found to be associated with formation of blood vessels (angiogenesis) and metastasis [42,43].…”

Ubiquitination-proteasome system: A new player in the pathogenesis of psoriasis and clinical implications

“…Later on, proteasome was found to be existed in the skin, with a propensity to be associated with age [65]. Recently, a high level of proteasome expression was detected in the plasma, tissue or cell of malignant melanoma [66], myeloid haematopoietic malignancies and other inflammatory disorders [67]. In 2004, Stoebner et al detected an elevated level of plasma proteasome in psoriasis patients [7].…”

Cross-reactivity between tumor MHC class I–restricted antigens and an enterococcal bacteriophage

“…hirae 13144, while MC38 cancer does not ( Figure S6A-B). PSMB4 is an oncogenic driver involved in proliferation and invasion (19) in a variety of malignancies such as glioblastoma (20), melanoma (21) and breast cancers (22), associated with dismal prognosis (19,20,22). CRISPR/Cas9-mediated genomic knock-in of the PSMB4 sequence replacing GSLARFRNI by GALARFRNI (with an SA exchange in position 2) or GSFARFRNI (with an LF exchange in position 3 equivalent to mut 3 of TSLARFANI) in MCA205 cells ( Figure S7) significantly affected tumor growth kinetics ( Figure S6C-D), suggesting that this PSMB4 epitope contributes to the oncogenic activity of PSMB4.…”