Terminal Unfolded Protein Responses-related genes predict prognosis and associate with proliferation and apoptosis in clear cell renal cell carcinoma

Abstract

Abstract Terminal unfolded protein response (TUPR), a self-destruct mechanism of cells, initiates when irreversible endoplasmic reticulum stress (ER stress) occurs and causes cell apoptosis. Current studies have shown that TUPR lead apoptosis in carcinoma, which plays an indispensable role in development of tumors. However, understanding the specific role of TUPR in ccRCC cells is important for the treatment of tumors.Based on 9 TUPR-associated genes, clusters of ccRCC patients were identified by unsupervised clustering. Prognostic models were constructed by LASSO regression and multivariate cox regression. Tunicamycin (Tm) was used to induce TUPR in ccRCC cells, and the gene expression, proliferation, and apoptosis of ccRCC cells under TUPR were investigated by RT-qPCR, EdU and immunofluorescence staining respectively. Our results show that ccRCC patients were distinguished into two clusters with various signatures. We confirmed that the TUPR-related prognostic model had a good predictive ability. 12 hours-Tm treatment induced TUPR in ccRCC cells and inhibited cell proliferation and promoted apoptosis. Silencing STT3B increased the sensitivity, inhibited the proliferation and promoted the apoptosis of ccRCC cells. Taken together, TUPR-associated genes were significantly correlated with clinical features of ccRCC patients, and were involved in ccRCC proliferation and apoptosis, which may become a new treatment option. STT3B may serve as a promising ccRCC therapeutic target.