Ring finger protein 19A is overexpressed in non‐small cell lung cancer and mediates p53 ubiquitin‐degradation to promote cancer growth

Abstract

The expression pattern, biological functions and the related mechanisms of the ring finger protein 19A (RNF19A) in non‐small cell lung cancer (NSCLC) remain poorly understood. This study aimed to explore the role of RNF19A, as well as the underlying potential mechanism, in the development of NSCLC. Here, we found that RNF19A was overexpressed in NSCLC tissues, and RNF19A expression in NSCLC tissue samples was associated with NSCLC carcinogenesis and poor outcome. RNF19A promoted the proliferation of NSCLC cells and inhibited apoptosis. RNF19A reduced p53, p21 and BAX expression and induced Cyclin D1, CDK4, CDK6 and BCL2 expression. The inhibitory effect of RNF19A knockdown on proliferation was partially rescued by p53 silencing. RNF19A interacted with p53, shortened p53 half‐life and mediated p53 ubiquitin‐degradation. Collectively, we suggest that RNF19A plays a critical oncogenic role in lung carcinogenesis by disrupting the function of p53. RNF19A may serve as a new biomarker and/or target for NSCLC management.

Identification and Quantification of Iron Metabolism Landscape on Therapy and Prognosis in Bladder Cancer

“…CYP2C8 can be regulated by GAS5/miR-382-3p in hepatocellular carcinoma and play an anticancer role ( Li and Chen, 2020 ). RNF19A was confirmed to be overexpressed in non-small cell lung cancer, which plays a carcinogenic role by destroying the function of p53 ( Cheng et al, 2021 ). CYP4Z1 was confirmed to be highly expressed in BLCA and positively correlated with the progression of histologic grade and pathologic stage ( Al-Saraireh et al, 2021 ).…”

A Composite Bioinformatic Analysis to Explore Endoplasmic Reticulum Stress-Related Prognostic Marker and Potential Pathogenic Mechanisms in Glioma by Integrating Multiomics Data

“…Ring Finger Protein 19A (RNF19A) encodes a protein that belongs to the ring fingers protein family, an E3 ubiquitin ligase [ 56 ]. RNF19A decreases p53 expression and its downstream signaling, binds to p53, and promotes its ubiquitination, thereby promoting nonsmall cell lung carcinoma (NSCLC) growth and progression [ 57 ]. Peroxidasin (PXDN) encodes a heme-containing peroxidase that is involved in extracellular matrix formation associated with prostate cancer [ 58 ].…”

Advances of E3 ligases in lung cancer

“…The ring finger protein 19 A (RNF19A) downregulates p53, p21, and B-cell lymphoma-2 (BCL2) associated X, apoptosis regulator (BAX) expression but upregulates Cyclin D1, cyclin dependent kinase 4 (CDK4), cyclin dependent kinase 6 (CDK6) and BCL2 expression in NSCLC cells. Moreover, RNF19A promotes proliferation and reduces apoptosis in NSCLC cells by interacting with, ubiquitinating and inducing proteasomal degradation of p53 [ 117 ] (see Fig. 3 ).…”

“…Although there are significant advances in lung cancer immunotherapy and targeted therapies, many patients still experience side effects and harmful effects of drug or radiation resistance, which can lead to recurrence and metastasis of lung cancer. There are numerous carcinogens involved in the occurrence and progression of lung cancer [ 117 ]. Also, oncogene mutation or inactivation may lead to lung cancer.…”