Up-regulation of RNF187 induces hepatocellular carcinoma cell epithelial to mesenchymal transitions

Abstract

Ring finger protein 187 (RNF187) has been identified to be a co-activator linking c Jun to Ras signaling. However, the expression and function of RNF187 in hepatocellular carcinomas (HCC) remains unclear. Here, we tried to determine the expression and roles of RNF187 in hepatocellular carcinomas (HCC).The expression of RNF187 was determined in HCC tissues and cell lines, and we found that RNF187 expressed highly in HCC tissues compared with the corresponding adjacent liver tissues both in mRNA and protein level, which was consistent with the result of immunohistochemistry on HCC tissue microarrays. In HCC cell lines, the level of RNF187 was positively associated with the HCC cells metastatic potential. By the RNF187 interference and cDNA transfection, we showed that the high level of RNF187 induced the HCC cells invasion and metastasis both in vitro and in vivo, as well as the high ability of colony formation.Mechanistically, we detected the high level of RNF187 promoted cell scatter by inducing epithelial-mesenchymal transition (EMT). Clinically, the high level of RNA187 was significantly correlated with a malignant phenotype, including larger tumor size, multiple tumors, and microvascular invasion. Importantly, high level of RNF187 correlated with HCC patients' shorter OS and lower disease free survival rates than those with low level of RNF187. Our results revealed that elevated expression of RNF187 induced hepatocellular carcinoma cell epithelial to mesenchymal transitions, and represented a novel marker for predicting the poor prognosis of HCC.

Regulation of Hippo signaling and triple negative breast cancer progression by an ubiquitin ligase RNF187

“…Previous studies showed that RNF187 is required for AP-1 mediated cell proliferation 20 . Besides recent studies showed that RNF187 could play an oncogenic role in several cancers [20][21][22][23] . For example, RNF187 could promote liver cancer progression via Norch1 signaling 21 .…”

“…Besides recent studies showed that RNF187 could play an oncogenic role in several cancers [20][21][22][23] . For example, RNF187 could promote liver cancer progression via Norch1 signaling 21 . However, in our current study, RNF187 functions as a tumor suppressor in TNBC progression.…”

RACO‐1 modulates Hippo signalling in oesophageal squamous cell carcinoma

“…25 In addition, FBW7, as a RING E3 ubiquitin ligase, can also cause ubiquitination and degradation of YAP at the k48 site. 26 Our current study indicated that 15,17,18 Our data showed that RACO-…”

High level of RNF187 contributes to the progression and drug resistance of osteosarcoma

“…Polyclonal rabbit anti-human RNF187 (1:200; Novus Biologicals, Cambridge, UK) was used to detect the RNF187 protein. RNF187 expression was evaluated according to the intensity and ratio of positive tumor cells as the previously described [6,13,16]. The two levels of RNF187 intensity of were classified according to the mean area of positive staining, and the cutoff value was 50% of tumor section, the ≥50 percent was positive, and negative was < 50 percent.…”

“…E3 ubiquitin ligases (E3s) are critical importance due to not only transfer ubiquitin to specific substrates [5]. Ring finger protein 187 (RNF187), a RING domain-containing ubiquitin E3 ligase, was lately verified to overexpressed in hepatocellular carcinoma and non-small cell lung carcinoma and advanced tumor development by inducing tumor cell epithelial-mesenchymal transition (EMT) [6,7]. Furthermore, RNF187 knockout was revealed to suppress the cellular proliferation via inhibiting the transcription of AP-1-related genes, and RNF187 overexpression activated Wnt and Ras pathways to accelerate the tumor formation in colon epithelial tumor [8].…”