Study On Mechanism Of CPT1A In Esophageal Squamous Cell Carcinoma Development

Esophageal squamous cell carcinoma(ESCC)is one of the common gastrointestinal cancer,with the development of the economy and the world’s aging population,the incidence of esophageal cancer showed an increasing trend.The mortality of esophageal cancer ranked fourth among all types of cancer.Currently,the use of a comprehensive treatment or surgery combined with radiotherapy improves the cure rate of esophageal cancer,but the survival rate after five years is still less than 20%.There are no obvious symptoms in the early time of esophageal cancer,so patients often miss the best time for treatment when they come to the hospital.Therefore,early diagnosis and identification of molecular markers associated with esophageal cancer has become a hot content of clinical research.Esophageal cancer occurrence and development is a multi-gene effects.Not only autoimmunity,environmental and other external factors are involved in this progress,but also many other factors.Such as abnormal expression of tumor suppressor genes or ncogenes,regulatory disorders of biological pathways and metabolism disorders.In our earlier study,we used whole-genome sequencing and comparative genomic hybridization to test 79 cases of tissue samples from ESCC patients.It showed that amplifications at 11q13.2 and deletions at 7q34 and 18q21.1-q23 are popular in ESCC.Besides,the amplification at 11q13.2 is an independent prognostic factor in ESCC.Then,we tested the relationship between 11q13.2 amplification and ESCC survival rate.We found that short-term survival in patients with ESCC and lymph node metastasis are related with abnormal Carnitine palmitoyltransferase 1A(CPT1A)amplifications.Immunohistochemical detection results showed that the short-term survival in patients with ESCC and lymph node metastasis are also related with the high expression of CPT1A.In our present study,we found that the ability of proliferation,migration and invasion in CPT1A high expressed ESCCs were significantly reduced after siRNA intervention,knocking down CPT1A expression can also increase the ability of apoptosis in ESCCs.We got the same result after the use of etomoxir,a specific inhibitor of CPT1A.These results suggest that CPT1A is a target gene at 11q13.2 and CPT1A plays an important role in ESCC.In order to further explore the molecular mechanisms of CPT1A in controlling esophageal squamous cancer cell proliferation,migration and invasion.We knocked down the expression of CPT1A in ESCCs and did the cDNA microarray detection.We found 11 significantly upregulated genes:PRB2,FAM153B,LOC101927136,CASC11,AKR1C1,CAMK1G,KCND1,DNAH17,MTERF4,MUC17 and SERPINB2;and 18 significantly down-regulated genes:KCNK2,TP53INP1,PPT1,SLC43A2,LOC100422737,SCARB2,BEND4,OAS1,ATP11A,DAG1,PLAU,KIAA0101,PARK7,RFK,ALDH1A3,LGALS1,SLC47A2,FZD1.Our study is important for researchers to reveal the role of the molecular mechanism in ESCCs and we hope to find a new candidate molecular targets for the clinical treatment of ESCC.