RNF114 Silencing Inhibits the Proliferation and Metastasis of Gastric Cancer

Abstract

RNF114 (E3 ubiquitin ligase RING finger protein 114) was first identified as a zinc-binding protein that promotes psoriasis development; however, its role in gastric cancer is still unclear. We explored the relationship between RNF114 and gastric cancer using bioinformatics and molecular biology techniques. The results showed that RNF114 was highly expressed in gastric cancer and negatively correlated with the patient's prognosis. Functional assays suggested that RNF114 silencing suppressed the proliferation and metastasis of gastric cancer cells to a certain extent. Further studies showed that RNF114 expression was potentially targeted by miR-218-5p and methylation modification, and mediated downstream EGR1 (early growth response 1) degradation by the ubiquitylation approach. Together, the present results highlight the detrimental effects of RNF114 overexpression in gastric cancer and contribute to a better understanding of the mechanisms underlying RNF114 functionality.

Stress induced phosphoprotein 1 overexpression controls proliferation, migration and invasion and is associated with poor survival in oral squamous cell carcinoma

“…The studies reported here also revealed that STIP1 and miR-218-5p are inversely correlated, and the transfection of OSCC cell lines with miR-218-5p mimics downregulated STIP1 which was followed by inhibition of proliferation, motility and invasiveness, similarly as seen with STIP1 silencing. Recently, miR-218-5p was reported to be downregulated in several cancers, including gastric, colorectal, ovarian, prostate, cervical and lung adenocarcinoma ( 41 – 46 ) and have different protein targets affecting cancer progression. Downregulation of miR-218-5p promoted OSCC invasion via activating CD44-ROCK signaling ( 47 ).…”

Early growth response-1 is a new substrate of the GSK3β-FBXW7 axis

“…However, it is quite surprising that very little is known as to how EGR1, a short-lived important transcription factor, is regulated by the UPS. Although two E3 ligases MDM2 and RNF114 were implicated in regulation of EGR1 turnover in leukemia and gastric cancer cells, respectively, both studies did not provide detailed characterization to convincingly show that EGR1 is indeed a substrate of these two E3 ligases [ 25 , 26 ].…”

“…Thus, the function of EGR1 in human cancer could be context dependent. While EGR1 is mainly regulated at the transcriptional levels [1] , EGR1 was also found to be regulated at the posttranslational levels, such as by phosphorylation [20] , [21] , [22] , [23] , acetylation [24] , sumoylation [22] , and possibly by ubiquitylation [ 25 , 26 ]. Whether and how EGR1 is subjected to ubiquitylation and degradation by SCF E3 ligase is totally unknown.…”

Transcriptional immune suppression and upregulation of double stranded DNA damage and repair repertoires in ecDNA-containing tumors

“…TMEM203 is a STING-centered signaling regulator implicated in inflammatory diseases 25 . RNF114 is a zinc-binding protein whose over-expression is an indicator of epithelial inflammation and implicated in various tumors 26 . 10 TAF4, a transcription initiation factor, when overexpressed, is implicated in ovarian cancer by playing a role in dedifferentiation that promotes metastasis and chemoresistance 27 .…”