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Long Non-Coding RNA AWPPH Promotes Postoperative Distant Recurrence In Resected Non-small Cell Lung Cancer By Upregulating Transforming Growth Factor Beta 1

Posted on:2021-03-14Degree:MasterType:Thesis
Country:ChinaCandidate:L X TangFull Text:PDF
GTID:2404330611958777Subject:Internal medicine (respiratory disease)
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Primary bronchial lung cancer,referred to as lung cancer,is a malignant tumor that originates from the bronchial mucosa or alveolar epithelium.The Global Cancer Report2014 published by the WHO shows that the incidence of lung cancer ranks first among men,second to breast cancer among women,and the mortality rate of lung cancer is much higher than all other malignancies,accounting for 19.4%.The clinical manifestations of lung cancer are complex,with no obvious clinical symptoms in early stages.As the disease progresses,tumors can cause cough,sputum or hemoptysis,chest pain,wheezing,hoarseness,dyspnea,fever,anemia,weight loss and cachexia when the tissue causes blockage,infiltration and hemoptysis.Almost two-thirds of the patients are already at the advanced stage due to clinical symptoms,and lung cancer is also one of the most prone to distant metastases,Without antitumor treatment,the average survival time is about six months.Lung cancer is a complex disease process with multiple genetic changes,multiple factors and multiple stages of development.The current treatment methods include surgery,chemotherapy,radiotherapy,molecular targeted therapy and biological therapy.Although the level of diagnosis and treatment of lung cancer is constantly improving,the long-term prognosis and long-term survival of lung cancer patients are not very optimistic.At present,due to the increased resistance to lung cancer,gene-targeted therapy has become a new hotspot in current research.Exploring and becoming familiar with newly discovered therapeutic targets and applying them to the clinical diagnosis and treatment of lung cancer will help improve the survival rate and improve the quality of life of patients with lung cancer.It has very important clinical research value and great practical significance.Combining genomic and transcriptional sequencing studies has identified many gene-driven mutations that are one of the causes of lung cancer.Importantly,these methods also reveal the widespread expression of "non-coding RNA"(including long-chain non-coding RNA),which affects biological responses by regulating the transcription or translation of m RNA.So far,most studies on the role of non-coding RNA have focused on long-chain non-coding RNAs that regulate m RNA translation through RNA interference pathways.Although many of their properties,such as expression patterns,are still unknown,long non-coding RNAs have key functions in transcription,post-transcription,and epigenetic regulation.In recent years,with the discovery of various new nc RNAs and regulatory functions,and the growing number of genetic elements involved in cancer development,nc RNAs are becoming a growing focus of cancer genomics research.Many studies have shown that the expression levels of certain lnc RNAs in metastatic tissues are significantly different from those in primary and normal tissues of cancer patients.Abnormal upregulation of lnc RNA in NSCLC is often classified as oncogenic lnc RNA.Carcinogenic lnc RNA has many functions,including maintaining cell growth and proliferation;avoiding growth inhibitors;ensuring continuous replication of DNA;promoting metastasis and invasion;inhibiting apoptosis and inducing angiogenesis;discovering new lnc RNAs that inhibit tumors.Lnc RNA that can inhibit tumor development is called "tumor-inhibiting lnc RNA".Therefore,Lnc RNA has received more attention in cancer research.Elucidating its function is important for understanding the mechanism of tumorigenesis,and is a prerequisite for further research and development of new therapeutic targets.Our study explored the role of lnc RNAAWPPH in the postoperative recurrence of patients with non-small cell carcinoma in order to provide sensitive molecular biological indicators for clinical treatment.Material/Methods A total of 128 patients were followed up for 3 years.Blood was extracted from each patient on the day of discharge,the day of the diagnosis of recurrence,or at the end of follow-up.Blood from 30 healthy controls was used as a control group.Patient were divided into 3 groups – a non-recurrence group(NR,n=54),a local recurrence group(LR,n=42),and a distant recurrence(DR,n=32)group – according to the follow-up results.Blood AWPPP was detected by q RT-PCR.AWPPH expression vectors were transfected into cells of human NSCLC cell lines.Cell migration and invasion were detected by Transwell migration and invasion assay,respectively.TGF-b1 expression was detected by Western blot analysis.Results Blood AWPPH levels were the highest in the DR group,followed by the LR and NR groups.The lowest blood AWPPH levels were observed in the control group.Blood AWPPH levels increased significantly in the DR group but not in the NR and LR groups during follow-up.Blood AWPPH levels were positively correlated with TGF-b1 m RNA levels in the DR group but not in the NR and LR groups during follow-up.AWPPH overexpression promoted cell migration and invasion and upregulated TGF-b1 expression.Conclusions Lnc RNA AWPPH can promote postoperative distant recurrence in resected NSCLC by upregulating TGF-b1.
Keywords/Search Tags:Non-Small-Cell Lung, Recurrence, Long Non-coding Ribonucleic Acid, Transforming Growth Factor beta1
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