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Published on: August 23, 2019
RNF150 suppresses papillary thyroid carcinoma with ASK1 ubiquitination presenting a direct target via inactivating
Wei Deng1,2, Jing Wu2, Wei Zheng3
1Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Abstract:
Papillary thyroid carcinoma (PTC) is the most prevalent cancer in endocrine system. However, the pathogenic mechanism underlying tumor recurrence remains unclear. RING finger protein (RNF) family plays a crucial role in cancers whereas the role of RNF150 in PTC requires investigation. Our study aimed to explore the function and molecular mechanism of RNF150 in PTC. Here, we extracted data from The Cancer Genome Atlas-THCA (TCGA-THCA) data set to investigate the expression and prognostic value of RNF150 in THCA. We found that RNF150 was lowly expressed in THCA and its high expression indicated favorable prognosis in THCA patients. RNF150 could inhibit the proliferation of PTC cells and suppress p38 phosphorylation both in vitro and in vivo. Meanwhile, the knockdown of RNF150 significantly promoted the proliferation of PTC cells and the phosphorylation of p38, which could be reversed by p38 inhibitor. Besides, RNF150 could interact with ASK1 and promoted its ubiquitination. The overexpression of ASK1 exerted opposite effects against RNF150 in PTC cells. In PTC specimens, RNF150 and ASK1 shared reversed expression pattern. In conclusion, our study revealed that RNF150 could suppress the proliferation of PTC by inactivating p38 pathway and promoting ASK1 ubiquitination, which provided novel targets for PTC treatment.
Insights
Ring finger protein 150 (RNF150) suppresses papillary thyroid carcinoma (PTC) growth by inhibiting the p38 pathway and promoting ASK1 ubiquitination. High RNF150 expression correlates with better prognosis in PTC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy, but its recurrence mechanisms are not fully understood.
- The role of the RING finger protein (RNF) family, specifically RNF150, in PTC pathogenesis requires further investigation.
Purpose of the Study:
- To investigate the function and molecular mechanism of RNF150 in papillary thyroid carcinoma.
- To analyze the expression and prognostic value of RNF150 in thyroid cancer using The Cancer Genome Atlas-THCA (TCGA-THCA) dataset.
Main Methods:
- Analysis of TCGA-THCA dataset for RNF150 expression and correlation with patient prognosis.
- In vitro and in vivo experiments to assess the effect of RNF150 on PTC cell proliferation and p38 phosphorylation.
- Investigation of RNF150 interaction with ASK1 and its ubiquitination status.
- Assessment of p38 pathway activity using a p38 inhibitor.
Main Results:
- RNF150 was found to be lowly expressed in THCA, with high expression indicating a favorable prognosis.
- RNF150 inhibited PTC cell proliferation and suppressed p38 phosphorylation both in vitro and in vivo.
- Knockdown of RNF150 promoted PTC cell proliferation and p38 phosphorylation, effects reversible by a p38 inhibitor.
- RNF150 interacted with ASK1, promoting its ubiquitination, and RNF150 and ASK1 showed reversed expression patterns in PTC specimens.
Conclusions:
- RNF150 suppresses PTC proliferation by inactivating the p38 pathway and promoting ASK1 ubiquitination.
- RNF150 represents a potential therapeutic target for papillary thyroid carcinoma treatment.
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