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The mechanism underlying the malignant biological behaviors of SKCM is not fully clear. Our study intended to verify the molecular mechanism of proteasome 26\u2009S subunit ATPase 2 (PSMC2) in malignant biological behaviors of SKCM. The Cancer Genome Atlas (TCGA) database was used to analyze the expression of PSMC2 in SKCM and its impact on prognosis. PSMC2 expression in 105 paired SKCM tissues was investigated by immunohistochemistry (IHC), its functional roles were verified using a series of cell experiments, and the underlying pathway was detected by protein-chip technology and gene set enrichment analysis. We found that PSMC2 was significantly upregulated in SKCN patients from TCGA datasets and verified in clinical SKCM tissues. Moreover, high PSMC2 was shown to closely correlate with the pathological stages and lymphatic metastasis of SKCM patients. Functionally, knockdown of PSMC2 suppressed the progression of SKCM through inhibiting cell proliferation, migration, and DNA damage in vitro as well as cell growth in vivo, whereas inducing apoptosis, cycle arrest in G2 phase. Similarly, pharmaceutical inhibition of proteasome with MG132 mimicked the PSMC2 knockdown induced defects in cell cycle arrest, apoptosis and proliferation, while overexpression of PSMC2 has the opposite effects. Mechanistically, the silence of PSMC2 remarkably elevated the pro-apoptotic proteins DR6, IGFBP-4, p21, and p53, while inhibited the anti-apoptosis protein TRAILR-3 and the proteins related to the Wnt signaling pathway. The present study revealed that PSMC2 participated in a positive regulation to promote the progression of SKCM through regulating the Wnt signaling pathway. Our findings may offer a new mechanism underlying the development and progression of SKCM, and a deeper understanding of PSMC2 may contribute to SKCM treatment.<\/jats:p>","DOI":"10.1038\/s41420-021-00727-2","type":"journal-article","created":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T08:02:52Z","timestamp":1635494572000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["PSMC2 knockdown suppressed tumor progression of skin cutaneous melanoma"],"prefix":"10.1038","volume":"7","author":[{"given":"Yanwen","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8702-8449","authenticated-orcid":false,"given":"Fazhi","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanyuan","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Luan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianying","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,29]]},"reference":[{"key":"727_CR1","doi-asserted-by":"crossref","unstructured":"Coricovac D, Dehelean C, Moaca E-A, Pinzaru I, Bratu T, Navolan D, et al. 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