Study On The Roles And Mechanism Concerning Overexpression Of Carnitine Palmitoyltransferase1C On The Survival Under Metabolic Stress In Papillary Thyroid Carcinoma

Thyroid cancer is one of the most common endocrine system malignancies in the world,accounting for 1.5% of systemic malignancies.while accounts for the first(30%)in the incidence of cancer in head and neckhe peak period of Thyroid cancer is generally the young-and-middle ages,male to female ? 1: 3.Thyroid cancer is usually divided clinically into 4 types: papillary carcinoma,follicular carcinoma,medullary carcinoma and undifferentiated carcinoma.Papillary thyroid cancer accounts for about 3/5 of adult thyroid cancer and and the whole children thyroid cancer.With the relatively low degree of malignancy,most of the tumors are centric.Cervical lymph node metastasis appears early,the prognosis is better.But it is worrying that the incidence of papillary thyroid cancer is still showing a rising trend year by year.The occurrence,development and metastasis of papillary thyroid carcinoma is a complex biological process involving multiple genes and multi-step parameters.Although the diagnosis and treatment of papillary thyroid cancer has made great progress,because of its intricate gene regulatory network,which involves a lot of pathogenesis of changing the of thyroid cancer by genes has not been fully elucidated so far.CPT1 family protein is a transmembrane integrin,which is related to the transmembrane transport of mitochondrial membrane chains.It is a fatty acid beta oxidative rate-limiting enzyme,plays an important role in cell fatty acid oxidation.Its family has three tissue-Specific family members: CPT1 A,CPT1B,CPT1 C.In recent years,it has been found that fatty acid beta-oxidation may be one of the main regulatory mechanisms for tumor metabolism adaptation.As an important member of the CPT1 family of fatty acid oxidative metabolic rate limiting enzymes,CPT1 C may be an important regulator of cancer cell metabolism and plays an important role in cancerous lesions.Therefore,this study preliminarily studied CPT1 C regulation of papillary thyroid cancer fatty acid oxidation and metabolism of the mechanism and biological significance.The significance of this study is to provide new ideas for the identification and treatment of patients with clinical thyroid cancer.And it may help to explain the mechanism forthe development of thyroid cancer from the perspective of metabolism,which also provides new targets and strategies for thyroid cancer treatment.Chapter 1 The role of carnitine acyltransferase 1C(CPT1C)in the developmentand progression of papillary thyroid carcinomaOur subject group focuss on the role of CPT1 C in papillary thyroid carcinoma,especially under metabolic stress.In this study,48 cases of papillary thyroid carcinoma specimens were collected.The m RNA level of CPT1 C in clinical specimens was detectedby q RT-PCR.To determine the role of CPT1 C in papillary thyroid carcinoma,the effect of CPT1 C on the proliferation,apoptosis,and cycle as well as migration of thyroid cancer cells was investigated by CPT1 C si RNA in thyroid cancer cells lines.On the basis of this,hypoxia stress and low glucose stress were constructed to detect the expression of CPT1 C in glucose deprivation and hypoxia models.The effects of CPT1 C up-regulation on the viability of thyroid cancer cells under glucose deprivationand hypoxia culture were studied,respectively.The results of our study show that CPT1 C is highly expressed in tumor tissues of thyroid carcinoma.And down-regulation of CPT1 C research can inhibits the proliferation of thyroid cancer cells,promotes cell apoptosis,and promotes cell G1 and S stagnation,while CPT1 C silencing can also inhibit the migration of thyroid cancer cells.In addition,hypoxia and glucose deprivation can promote CPT1 C expression;silencing CPT1 C can promote hypoxia and glucose deprivation conditions of thyroid cancer cell death,while high expression of CPT1 C can promote thyroid cancer cell survival under the hypoxia and glucose deprivation stress.Chapter 2 The relationship between carnitine acyltransferase 1C(CPT1C)and theup-regulation mechanism of papillary thyroid carcinomaAfter constructing the metabolic stress model(hypoxia and glucose deprivation model),the expression of CPT1 C and the phosphorylation of AMPK were detected by western blot.Under normal circumstances,different concentrations of AICAR were used to stimulate thyroid cancer cells KTC-1,Under the condition of glucose deprivation and hypoxia,CPT1 C expression was detected by Compound C co-culture of thyroid cancer cell KTC-1 under different concentrations.Our study showed that CPT1 C expression was regulated by AMPK.