Pan‑cancer analysis of the carcinogenic role of WSB2 in human tumors.

Abstract

WD repeat and SOCS box containing 2 (WSB2) is an E3 ubiquitin ligase that might be involved in regulating protein stability, thus performing important roles in the development of different types of cancer. However, the biological significance of WSB2 in pan‑cancer is unclear. Pan‑cancer analysis with the online platforms UALCAN and TIMER2.0. revealed that the expression levels of WSB2 were increased in various types of tumors, including breast invasive carcinoma, uterine corpus endometrial carcinoma, liver hepatocellular carcinoma and were decreased in other types such as colon adenocarcinoma, kidney chromophobe and rectum adenocarcinoma, compared with that in their corresponding normal tissues. In addition, pan‑cancer analysis using The Human Protein Atlas database indicated that WSB2 expression levels vary across different cancer types. Reverse transcription‑quantitative PCR (RT‑qPCR) revealed that WSB2 expression varied in 11 different cell lines. Promoter activity analysis indicates that specificity protein 1 carries out a key role in regulating WSB2 expression by binding to its promoter region. UALCAN and Kaplan‑Meier analysis were used to assess the pathological stage and prognostic value of WSB2 in pan‑cancer. Finally, overexpression of WSB2 promoted the proliferation and migration of MCF‑7 and MDA‑MB‑231 cells. Western blotting revealed that WSB2 increased the levels of vimentin, Snail and ERK1/2, and inhibited the expression of p53 and E‑cadherin in MDA‑MB‑231 and MCF‑7 cells. Transcriptome sequencing analysis identified 118 differentially expressed genes associated with WSB2 overexpression, which were mainly enriched in the 'p53 signaling pathway'. Furthermore, the expression of NUPR1 (encoding nuclear protein 1, transcriptional regulator), LDLRAD4 (encoding low density lipoprotein receptor class A domain containing 4) and MDM2 (encoding mouse double min 2) were verified by RT‑qPCR. Overall, the present study contributes to the understanding of the carcinogenic role of WSB2 in different types of cancer.