RNF180 mediates STAT3 activity by regulating the expression of RhoC via the proteasomal pathway in gastric cancer cells

Abstract

Ring finger protein 180 (RNF180) is an important member of the E3 ubiquitin ligase family. As a tumor suppressor gene, RNF180 is significantly associated with the prognosis of patients with gastric cancer (GC) and can inhibit the proliferation, invasion, and migration of GC cells. Signal transducer and activator of transcription 3 (STAT3) are considered one of the most common oncogenes in human cancers with a key role in GC progression. In this study, we explored the molecular signaling pathways by which RNF180 could potentially regulate STAT3 through transcriptomics and proteomics experiments. Here, we found RNF180 overexpression could suppress STAT3 phosphorylation in GC cells. Ubiquitin label-free experiments showed that the ubiquitination level of Ras homolog gene family member C (RhoC) is significantly increased in GC cells transfected with an RNF180 expression vector (RNF180-GFP vector) compared with cells transfected with an empty vector (vehicle vector). We subsequently demonstrated that RNF180 could directly combine with RhoC and promote the ubiquitination and degradation of RhoC protein in GC cells. The phosphorylation level of STAT3 significantly decreased in GC cells after RhoC knockdown using small hairpin RNA (shRNA). Together, these results reveal RNF180 could inhibit GC progression by reducing the phosphorylation of STAT3 via the ubiquitination and degradation of RhoC protein in GC cells. Thus, the protein may be considered a novel therapeutic target for patients with GC.

DNMT3A-mediated silence in ADAMTS9 expression is restored by RNF180 to inhibit viability and motility in gastric cancer cells

“…Through using of the online GEPIA database and IHC staining of 135 GC tissues from our center, we found a significant positive correlation between the expression of RNF180 and ADAMTS9. According to our previous studies, RNF180 is a suppressor gene that inhibits LN metastasis in GC and could act as an independent prognostic indicator of gastric cancer 19 , 25 . RNF180 is an E3 ubiquitin ligase that belongs to the ubiquitin-proteasome system and plays an important role in post-translational modification, which actually influence several processes of oncogenesis and tumor progression 26 .…”

Curcumin inhibits the viability, migration and invasion of papillary thyroid cancer cells by regulating the miR‑301a‑3p/STAT3 axis

“…These observations indicated that miR-301a-3p was a suppressor of STAT3 protein expression and the JAK/STAT signaling pathway in TPC-1 cells. STAT3 is considered to be one of the most common oncogenes in human cancers and plays a key role in PTC progression ( 17 , 55 ). It was further demonstrated that curcumin and miR-301a-3p mimics reduced the levels of phosphorylated JAK1, JAK2, JAK3, STAT1 and STAT2 via the targeting of STAT3 by miR-301a-3p, whereas the overexpression of STAT3 abolished the suppressive effect of curcumin on this signaling pathway.…”

“…Furthermore, the overexpression of STAT3 reversed the inhibitory effects of curcumin on the viability, migration and invasion of TPC-1 cells. It has been reported that suppression of STAT3 activity or expression inhibits human cancer progression ( 55 , 63 , 64 ). Curcumin has been demonstrated to promote PTC cell apoptosis by increasing DNA damage, endoplasmic reticulum stress and the PI3K/Akt signaling pathway ( 16 , 42 , 59 ).…”

ICT1 Promotes Osteosarcoma Cell Proliferation and Inhibits Apoptosis via STAT3/BCL-2 Pathway

“…STAT3 is a critical signal protein that is involved in a variety of growth factors and cytokines, which triggers a variety of biological outcomes, including cell growth, differentiation, and survival [ 11 ]. Moreover, STAT3 is reported to be an important oncogene in many malignant tumors.…”