RNF183 promotes proliferation and metastasis of colorectal cancer cells via activation of NF-κB-IL-8 axis

Abstract

Colorectal cancer (CRC) is one of the most common malignant tumors worldwide, which is a heterogeneous disease and main risk factors are associated with inflammation, family history, genetic mutations, epigenetics, and so on. Ring finger domain proteins have been reported involved in carcinogenesis, whereas their roles in CRC are rarely studied. Here, we reanalyzed the expression of 202 RNF family members in CRC using published microarray data from GEO database and found that RNF183 is markedly upregulated in tumor tissues. RNF183 high expression is significantly associated with tumor size (P=0.012), tumor invasive depth (P=0.004), TNM stage (P=0.01), and distant metastasis (P=0.009). CRC patients with high expression of RNF183 have poor overall survival (P<0.001) and progression-free survival (P<0.001). Functional studies suggest that RNF183 facilitates growth, migration, and invasion of CRC cells in vitro and promotes tumor proliferation and metastasis in vivo. Mechanistically, RNF183 activates NF-κB signal pathway through P65 and stimulates the transcription of multifunctional chemokine IL-8. Blockage of NF-κB by small molecule inhibitor or depletion of IL-8 by siRNA attenuates the function of RNF183 to promote cell migration. Moreover, the regulation of RNF183 on IL-8 transcription and cell viability/motility is dependent on its E3 ubiquitin ligase activity. Our study provided proof of principle to show that RNF183 promotes proliferation and metastasis of CRC cells via activation of NF-κB-IL-8 axis.

Semaphorin 7A promotes EGFR-TKI resistance in EGFR mutant lung adenocarcinoma cells

“…Transcriptome analysis revealed that Sema7A expression was significantly higher in EGFR-Mut-expressing cells than in cells expressing the WT receptor ( Figure 1B and Table 1; all gene expression data have been submitted to GEO, accession number GSE104494). Also upregulated were Lgr6 and Rnf183, which have been implicated in lung cancer stem-like cells and progression of colon cancer, respectively (30,31). Therefore, we focused on SEMA7A.…”

Long noncoding RNA TSLNC8 suppresses cell proliferation and metastasis and promotes cell apoptosis in human glioma

“…The results of the present study suggested that TSLNC8 was downregulated in human glioma, which was associated with increased cell proliferative rate and cell metastasis, as well as the decreased cell apoptotic capacity in human glioma cell lines; TSLNC8 may be a potential therapeutic target for cancer patients in clinic. Cell proliferation and cell metastasis are two primary manifestations in the majority of malignancies (24,25). Initiation of metastasis requires invasion, which was examined in the present study via Transwell and wound-healing assays.…”

NFAT5 up-regulates expression of the kidney-specific ubiquitin ligase gene Rnf183 under hypertonic conditions in inner-medullary collecting duct cells

“…RNF183 has been described as a ubiquitin ligase, which is expressed in normal colonic epithelial cells and colorectal cancer cells (19,20). In addition, we previously reported that Rnf183 mRNA expression in the kidney is ϳ324-fold higher than in the colon (21); however, RNF183 protein expression in the kidney remains unclear.…”

“…(ii) In the colon, RNF183 degrades IB␣, thereby inducing NF-B activation, which might contribute the pathogenesis of IBD (19). (iii) In the colorectal cancers, RNF183 induces the activation of NF-B and expression of its downstream gene, IL8, resulting in increased proliferation and metastasis of colorectal cancer cells (20). However, FATE1 expression is restricted to cancer or testis and is absent in the other tissues, such as the kidney (45).…”

“…RING finger protein 183 (RNF183) is a member of the RNF family, which functions as a ubiquitin ligase (18). Previous studies have demonstrated that RNF183 mRNA expression in the colon of patients with inflam-matory bowel disease (IBD) and colorectal cancers was ϳ5and 2-fold higher than that in control subjects; in these patients, RNF183 promotes intestinal inflammation (19) and proliferation and metastasis of cancers (20), respectively. On the contrary, we previously demonstrated that RNF183 was specifically expressed in human and mouse kidney, and that mouse Rnf183 mRNA expression in the kidney was ϳ324fold higher than in the colon (21).…”