<p>RNF128 Promotes Malignant Behaviors via EGFR/MEK/ERK Pathway in Hepatocellular Carcinoma</p>

Abstract

Background: The ubiquitin-proteasome system participates in the pathogenesis and progression of hepatocellular carcinoma (HCC). As an E3 ubiquitin ligase, RNF128 has been proved vital in carcinogenesis, whereas, little is known about the oncogenic mechanisms of RNF128 in HCC. Materials and Methods: Through tissue microarray from HCC patients, we analyzed RNF128 expression and its relationship with clinical outcomes in HCC. Western blot and quantitative realtime polymerase chain reaction (qRT-PCR) were performed to examine expression levels of RNF128 in HCC tissues and cell lines. Effects of RNF128 on HCC cellular biological functions and the potential mechanism were evaluated through knockdown and overexpression assays in vitro and in vivo methods. Results: RNF128 expression was found to be remarkably elevated in HCC tissues compared with adjacent normal tissues. Furthermore, the overexpression of RNF128 enhanced hepatoma cells proliferation, colony formation, migration, invasion, and apoptotic resistance both in vitro and in vivo. Mechanistically, RNF128 activated EGFR/MEK/ERK signaling pathway and the EGFR inhibitor, gefitinib partially reversed RNF128-enhanced proliferation, invasion, and migration in hepatoma cells. Conclusion: RNF128 promotes HCC progression by activating EGFR/MEK/ERK signaling pathway, which might function as a novel prognostic molecular signature with the potential to be a candidate therapeutic target for HCC patients.

Gut commensal bacteria enhance pathogenesis of a tumorigenic murine retrovirus

“…Rnf128 and Serpinb9b proved to be critical for leukemia development in RL-MuLV-infected SPF mice (Figure 5A). In line with our results, overexpression of the members of the ovalbumin family of serpins, to which Serpinb9b belongs, as well as Rnf128, are markers for poor prognosis in some human cancers [(Bai et al, 2020; ten Berge et al, 2002; Uhlen et al, 2017) and our own analysis of previously published data (Bolouri et al, 2018)]. A homolog for Serpinb9b has not been identified in humans, but related family member, human proteinase inhibitor 9 (SerpinB9) inhibits perforin-mediated cytotoxic T lymphocyte (CTL) cytotoxicity (Medema et al, 2001).…”

RING finger protein 128 (RNF128) regulates malignant biological behaviors of colorectal cancer cells via PI3K/AKT signaling pathway

“…Recently, RNF128 has been shown to be responsible for tumorigenesis and metastasis of human cancers. Emerging evidence has suggested that RNF128 is aberrantly expressed in melanoma, esophageal cancer, bladder cancer, and hepatocellular carcinoma (HCC; Bai et al, 2020; Gao et al, 2019; Lee et al, 2016; Wei et al, 2019). Bai et al (2020) reported that HCC patients had a higher expression of RNF128 in tumor specimens than in matched para‐cancerous samples, and its high expression had a significant correlation to tumor size, TNM classification, and adverse oncological outcomes of HCC patients.…”

“…Emerging evidence has suggested that RNF128 is aberrantly expressed in melanoma, esophageal cancer, bladder cancer, and hepatocellular carcinoma (HCC; Bai et al, 2020; Gao et al, 2019; Lee et al, 2016; Wei et al, 2019). Bai et al (2020) reported that HCC patients had a higher expression of RNF128 in tumor specimens than in matched para‐cancerous samples, and its high expression had a significant correlation to tumor size, TNM classification, and adverse oncological outcomes of HCC patients. A series of experimental study on the biological functions of HCC cells revealed that RNF128 inhibited cell apoptosis and promoted HCC proliferation, migration, and invasion by activating the EGFR/MEK/ERK pathway (Bai et al, 2020).…”

“…These findings suggested that the RNF protein family contributes to the tumorigenesis and metastasis of human cancers. Recent studies identified a novel member of RNF protein family, RNF128 (also named as Grail), which was aberrantly expressed in melanoma and hepatocellular carcinoma and esophageal cancer and played a carcinogenic role in these malignancies (Bai et al, 2020; Gao et al, 2019; Wei et al, 2019). However, little is known about the biological function of RNF128 and its underlying mechanism in the pathogenesis of CRC.…”

Upregulation of hsa_circ_0002003 Promotes Hepatocellular Carcinoma Progression

“…Despite recent advances in targeted therapies for HCC, therapeutic responses in patients with HCC patients remain poor. Thus, it is imperative to develop effective therapeutic strategies against HCC to improve patient survival [7,8].…”