RNF112, Whose Transcription is Regulated by KLF4, Inhibits Colorectal Cancer Growth Via Promoting Ubiquitin-dependent Degradation of NAA40

Overview

Journal Cell Biol Toxicol

Publisher Springer

Specialties Cell Biology
Toxicology

Date 2025 Jan 5

PMID 39757327

Authors

Chunfei Li

Wenzheng Guan

Donghua Geng

Yong Feng

Affiliations

Soon will be listed here.

Abstract

Background: RING finger protein 112 (RNF112) exerts a key role in human tumors. However, its biological function in colorectal cancer (CRC) has not been discussed. We aimed to explore the function and molecular mechanism of RNF112 in CRC.

Results: In this study, RNF112 expression was notably decreased in CRC tissues and cells. Clinical analysis revealed a significant association between low RNF112 expression and tumor size, N classification and TNM stage. In vitro experiments demonstrated that overexpression of RNF112 repressed cell viability, promoted cell cycle arrest and apoptosis, while knocking down RNF112 had the opposite function. The tumor formation results in nude mice supported that RNF112 overexpression exerted anti-tumor effects by inhibiting cell growth and promoting cell apoptosis. Mechanistically, Krüppel-like factor 4 (KLF4) acted as an upstream regulator of RNF112 by mediating its transcription. Furthermore, we explored the downstream mechanism of RNF112 and discovered that it promoted ubiquitination and degradation of oncoprotein N-alpha-acetyltransferase 40 (NAA40) through ubiquitin ligase activity. In addition, overexpression of NAA40 eliminated the effect of RNF112 overexpression on CRC tumorigenesis.

Conclusions: In summary, our findings confirm that RNF112, whose transcription is regulated by KLF4, inhibits CRC growth through promoting ubiquitin-dependent degradation of NAA40. We have unraveled the mechanism of KLF4-RNF112-NAA40 axis in CRC, which shed light on the therapeutic strategies for this disease.

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