The Mechanism Of Ubiquitin Ligase Pellino-1 In The Pathogenesis Of Tri-negative Breast Cancer

In China,the health burden of cancer increased year by year.Every year more than 2 million people are diagnosed with cancer and nearly 1 million people die from cancer.The breast cancer has become the most common cancer among Chinese women Like most other countries.In recent years,the second most common cause of malignant tumors in China is breast cancer.There are approximately 200,000 new cases each year.Moreover,the rate of new breast cancer and the number of deaths in China has increased around the world.Therefore,the discovery,diagnosis,research and treatment of breast cancer urgently need to be improved.Epithelial to mesenchymal transition(EMT)refers to the phenomenon of epithelial cells transforming into mesenchymal cells under specific physiological and pathological conditions.EMT plays an important role in embryonic development,chronic inflammation,tissue remodeling,cancer metastasis,and multiple fibrotic diseases.Its main features are the reduction of the expression of cell adhesion molecules(such as E-cadherin),the conversion of cytoskeleton cytoskeleton into vimentin-based cytoskeleton and the morphology of mesenchymal cells.Current research shows that EMT is a pathological process leading to tumor progression and is associated with invasion and metastasis.This topic mainly studies the EMT process of breast cancer cells and explores the molecular mechanism of breast cancer invasion and metastasis.The Pellinos protein family is an E3 ubiquitin ligase,with three evolutionarily conserved members,including Pellino-1,Pellino-2,and Pellino-3.Pellino-1 has K48 E3 ubiquitin ligase activity,but also K63 E3 ubiquitin ligase activity.Therefore,Pellino-1 has complex functions and there is a huge difference in the role of different signaling pathways in different cells.This topic mainly studies the mechanism of action of Pellino-1 in the development of breast cancer.Pellino-1 has played a more prominent role especially in the triple negative breast cancer.During the experiment,we used immunohistochemical method to detect the microarray of breast cancer cases and found that the expression of Pellino-1 in breast cancer tissues was significantly higher than that of the adjacent tissues.In multiple human breast cancer clinical sample tissues collected,it was found that the Pellino-1 protein level was significantly increased,and the mRNA level was also significantly increased.At the same time,we examined the expression of Pellino-1 protein in two types of normal breast cells and six breast cancer cell lines,and the results were consistent.In particular,the expression of Pellino-1 protein was higher in triple-negative breast cancer cell lines.By further exploring the mechanism of action of Pellino-1 in breast cancer,we found that knocking down the Pellino-1 gene can affect the morphological characteristics of breast cancer cells,such as the proliferation and invasion of breast cancer cells,and cell dryness is also significantly reduced.In subsequent experiments,we examined the molecular mechanism of action of Pellino-1 in triple-negative breast cancer cells.The expression of EMT-related proteins in cells was detected by Western Blot.The results showed that knockdown of Pellino-1 can effectively inhibit the expression of Snail,Slug,N-cadherin,and vimentin and activate the expression of E-cadherin These results show that knocking down Pellino-1 can inhibit the EMT process of triple negative breast cancer cells.In addition,by real-time quantitative PCR,the results showed that the mRNA level of e-cadherin was decreased after the knockdown of Pellino-1 gene,while at the same time,after the expression of the Snail/Slug,the phenomenon was reversed.The interaction between Pellino-1 and Snail/Slug was detected by immune coprecipitation.The results of the microarray also indicated that the expression of Pellino-1 and Snail/Slug protein was positively correlated.Therefore,Pellino-1 affected the breast cancer cell's EMT process by interacting with Snail/Slug,thereby promoting the development of breast cancer.So,Pellino-1 may be a potential target for breast cancer treatment.To sum up,the ubiquitin ligase Pellino-1 can enhance the proliferation and invasion of breast cancer cells and promote the EMT process,thereby promoting the metastasis and development of breast cancer.Therefore,this study provides a new basis for the prevention and treatment of breast cancer,especially for the follow-up study of triple negative breast cancer.