TRIM27 interacts with Iκbα to promote the growth of human renal cancer cells through regulating the NF-κB pathway

Abstract

Background The tripartite motif (TRIM) family proteins exhibit oncogenic roles in various cancers. The roles of TRIM27, a member of the TRIM super family, in renal cell carcinoma (RCC) remained unexplored. In the current study, we aimed to investigate the clinical impact and roles of TRIM27 in the development of RCC. Methods The mRNA levels of TRIM27 and Kaplan–Meier survival of RCC were analyzed from The Cancer Genome Atlas database. Real-time PCR and Western blotting were used to measure the mRNA and protein levels of TRIM27 both in vivo and in vitro. siRNA and TRIM27 were exogenously overexpressed in RCC cell lines to manipulate TRIM27 expression. Results We discovered that TRIM27 was elevated in RCC patients, and the expression of TRIM27 was closely correlated with poor prognosis. The loss of function and gain of function results illustrated that TRIM27 promotes cell proliferation and inhibits apoptosis in RCC cell lines. Furthermore, TRIM27 expression was positively associated with NF-κB expression in patients with RCC. Blocking the activity of NF-κB attenuated the TRIM27-mediated enhancement of proliferation and inhibition of apoptosis. TRIM27 directly interacted with Iκbα, an inhibitor of NF-κB, to promote its ubiquitination, and the inhibitory effects of TRIM27 on Iκbα led to NF-κB activation. Conclusions Our results suggest that TRIM27 exhibits an oncogenic role in RCC by regulating NF-κB signaling. TRIM27 serves as a specific prognostic indicator for RCC, and strategies targeting the suppression of TRIM27 function may shed light on future therapeutic approaches.

A Novel Gene Signature of Tripartite Motif Family for Predicting the Prognosis in Kidney Renal Clear Cell Carcinoma and Its Association With Immune Cell Infiltration

“…Silencing or genetic knockout of TRIM27 ubiquitination-dependently or -independently inhibits malignant biological behavior in breast, colorectal, and ovarian cancers ( 43 – 45 ). The expression of TRIM27 in RCC is a specific prognostic indicator, and its overexpression accelerates cell proliferation by promoting IκBα ubiquitination and inducing the activation of NF-κB signaling ( 46 ). Although more TRIM13 , 35 , and 55 mRNA was expressed in KIRC tumor tissues, this might favor a better clinical prognosis for patients with KIRC.…”

Emerging roles of TRIM27 in cancer and other human diseases

“…Under various stimuli, IκBs could be phosphorylated, whose subsequent proteasomal degradation could uncover the NLS of NF-κB and make it translocate into the nucleus to promote the expression of downstream genes ( Yamamoto and Gaynor, 2001 ). Additionally, TRIM27 was reported to interact with IκBα and lead to the ubiquitination of IκBα ( Xiao et al, 2021 ). Meantime, TRIM27 could promote the activation of NF-κB signaling.…”

“…Meantime, TRIM27 could promote the activation of NF-κB signaling. Taken together, TRIM27 might regulate NF-κB signaling by ubiquitinating IκBα ( Xiao et al, 2021 ).…”

“…In 2018, approximately 400,000 patients were diagnosed with renal cell carcinoma ( Jonasch et al, 2014 ; Bray et al, 2018 ). TRIM27 was reported to promote the tumor growth of RCC cell lines in vivo and vitro ( Xiao et al, 2021 ). Furthermore, the expression of TRIM27 expression was positively related to NF-κB expression in RCC patients and blocking NF-κB pathway overturned the TRIM27-mediated effects.…”

“…Furthermore, the expression of TRIM27 expression was positively related to NF-κB expression in RCC patients and blocking NF-κB pathway overturned the TRIM27-mediated effects. ( Xiao et al, 2021 ). Additionally, TRIM27 could bind to Iκbα, an inhibitor of NF-κB, to promote its ubiquitination, which led to the activation of NF-κB pathway ( Xiao et al, 2021 ).…”