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Mechanism Of C-Raf Kinase Binding Protein RCN2 In Lung Carcinogenesis

Posted on:2020-09-20Degree:MasterType:Thesis
Country:ChinaCandidate:P FanFull Text:PDF
GTID:2404330599955969Subject:Medicinal chemistry
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.Lung cancer is the most malignant tumor with the highest morbidity and mortality in the world.On a global scale,lung cancer has already occupied the top of the malignant tumor mortality rate.Even the sum exceeds breast cancer,prostate cancer and colorectal cancer.In 2017,a total of 3.93 million people were diagnosed with cancer in China,with an average of 7.5 people per minute suffering from cancer,and about 10,000 people were diagnosed with cancer every day.Among these cancer patients,the number of patients with lung cancer,stomach cancer,colorectal cancer,liver cancer,and breast cancer is in the top five.According to the National Cancer Center,among all malignant tumor patients,lung cancer patients accounted for 78.7%,followed by gastric cancer: 40.3%,colorectal cancer: 38.8%,and liver cancer: 37%.The lowest rates of cancer were cervical cancer: 11.1%,brain tumor: 10.6%,and pancreatic cancer: 9.5%.According to the above data analysis,the cancer rate of lung cancer is almost 7 times that of low-grade tumors such as cervical cancer,brain tumor and pancreatic cancer.Not only that,lung cancer is the most common among men,and second only to breast cancer among female patients.This shows that lung cancer has become the most deadly "killer" threatening human health.Therefore,for the study of the mechanism of lung cancer,it is imperative to seek new therapeutic targets.In the study of malignant tumors,we found that mutation of Raf protein kinase is one of the main causes of normal cell carcinogenesis.There are also three subtypes of Raf protein kinase:(A,B and C)-Raf.Each subtype mutation plays a role in different types of cancer.Analysis of the data revealed that C-raf is closely related to small cell lung cancer in lung cancer.At the same time,it is also abnormally expressed in tissues of lung cancer.This suggests that C-raf protein kinases and phase-associated binding proteins may be potential new targets we are looking for.C-Raf and its related proteins specifically affect how tumors occur,which is something we need to pay close attention to.Studies this year have shown that the mitogen-activated protein kinase(MAPK)signaling pathway carries many different types of signals and also mediates many cellular functions.In addition to cell growth,proliferation,cell differentiation,cell transfer and other reactions,it also controls immune system response and neuronal transmission.The Raf-MEK-ERK1/2 signaling pathway is a major pathway for cell-cell signaling.One of the main factors of normal cell carcinogenesis is the abnormal conduction and abnormal regulation of this signaling pathway.RCN2(Reticulocalbin2)is a secreted protein widely present in high-grade animal cells,which is an important member of the CREC family of proteins.Other members of this family,including RCN2,mediate different types by binding to second messenger calcium ions in the body.Cell function.These cellular functions include: cell growth,cell migration,cell differentiation,and the like.Not only that,but it also mediates the invasion and abnormal differentiation of cancer cells.Not only that,RCN2 can also bind to different proteins,mediating different kinds of diseases.Including the absorption of vitamin D,the differentiation of extraembryonic endoderm,mediating the toxicity of snake venom.It is also abnormally expressed in liver cancer,colorectal cancer,and cervical cancer.Although there is currently evidence that RCN2 plays a key role in a variety of cancers,no studies have yet shown its role in lung cancer.It was found that C-raf can specifically bind to RCN2,so a cell line overexpressing and knocking out of RCN2 was constructed in vitro.In addition,cell scratch test,cell dry globule experiment,TRANSWELL experiment and chemical drug sensitivity new experiment were carried out in the constructed cell line.After the experiment,it was found that the silencing cells constructed based on the lung cancer H1299 cell line showed a decrease in proliferation rate and were sensitive to chemical drugs such as etoposide and cisplatin.In the cell scratch test and the TRANSWELL experiment,it was found that the knockout of H1299 cells was significantly inhibited.In the cell dry globule experiment,it was found that the H1299 knockout cells showed a spherical decrease.In contrast,H1299 cells overexpressing RCN2 showed the opposite effect.This study shows that RCN2 plays an important role in lung cancer H1299 cells.After knocking out RCN2,cell growth,cell migration,cell dryness,etc.are inhibited,and chemotherapy drugs such as etoposide and cisplatin are compared.sensitive.The over-expressed one is just the opposite.The role of RCN2 in lung cancer has not been studied yet,and this study explored the pathogenesis of RCN2 in lung cancer.The experimental results show that RCN2 is promising as a new drug target for the treatment and diagnosis of lung cancer.
Keywords/Search Tags:lung cancer, RCN2, tumor, treatment, gene silencing high expression
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