Literature citations

RNF113A targeted by miR-197 promotes proliferation and inhibits autophagy via CXCR4/CXCL12/AKT/ERK/Beclin1 axis in cervical cancer.

Ring Finger Protein 113 (RNF113A), an ubiquitin E3 ligase, is genetically associated with many biological processes, including proliferation, differentiation, cell death, and neurogenesis. Recently, RNF113A has been found to be an abnormal expression in many diseases, such as X-linked trichothiodystrophy syndrome and esophageal cancer. Here, we explore the potential mechanism of RNF113A in the progression of cervical cancer (CC). In this study, we evaluated the expression level and biological function of RNF113A in CC both in vitro and in vivo by bioinformatic prediction, DIA proteomic analysis, compensation experiment, Co-IP, dual-luciferase reporter assay and nude mouse xenograft to identify the RNF113A-associated autophagy pathways involved with tumorigenesis. Consistent with the prediction from biological information analysis, we found that RNF113A was highly expressed in human CC tissues and cells. In addition, this study illustrated that the high expression of RNF113A dramatically promoted proliferation and suppressed autophagy both in vitro and in vivo. In contrast, low expression of RNF113A enhanced autophagy activities and inhibited tumor growth in CC. We also found that miRNA-197, the level of which (negative correlation with RNF113A) declined in human CC, directly restrained the expression of RNF113A. Mechanistically, proteomic and mechanistic assays uncovered that RNF113A confirmed as the direct downstream target of miR-197, promoted proliferation and restrained autophagy in CC not through direct ubiquitination degradation of autophagy marker Beclin1 but via CXCR4/CXCL12/AKT/ERK/Beclin1 signal transduction axis. In summary, we found a new miR-197/RNF113 A/CXCR4/CXCL12/AKT/ERK/Beclin1 regulation pathway that plays an important part in the survival and progression of CC.

Related UniProtKB entries

Browse all 9 entries
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.
FeedbackHelp