The Function And Mechanism Of Long Non-coding RNA HUESCC-lncRNA2 In Esophageal Squamous Cell Carcinoma

Background:Esophageal squamous cell carcinoma(ESCC),a primary histologic type of esophageal carcinoma in Asia,is the eighth most common cancer worldwide and the sixth most common cause of death from cancer,Esophageal squamous cell cancer is one of the most virulent and aggressive tumors in solid tumor.Despite the development of new treatment modalities including chemoradiotherapy(CRT)alone or as an adjunct prior to surgery,diagnostic technologies,and preventive approaches of this disease,the majority of patients with ESCC are diagnosed at an advanced stage and die within 24-48months after operation because of recurrence and metastasis.The crude mortality rate of esophageal cancer remained with a 5-year survival rate less than 30%.The long non-coding RNAs(IncRNAs),are new members of ncRNAs,which is with limited or no protein-coding capacity,they have been found to participate in a large range of biological processes,including modulation of apoptosis and invasion,reprogramming stem cell pluripotency,and parental imprinting.Methods:Using IncRNA microarray,we detected the expression levels of several ESCC related differentially expressed IncRNAs,and finally determined HUESCC-lncRNA2 for further study.Expression of HUESCC-lncRNA2 was analyzed in 110 ESCC tissues and eight ESCC cell lines using quantitative polymerase chain reaction(qPCR)assays.We further analyzed whether there was an association between HUESCC-lncRNA2 expression and specific clinicopathological parameters in patients with ESCC.Small interfering RNA was used to knock down HUESCC-lncRNA2 expression to further explore its role in tumor progression.MTS assay was perfumed to test cell viability in vitro(OD=490 nm),and cell invasion and migration were investigated by transwell.We further detected the HUESCC-lncRNA2 expression on protein level.Results:HUESCC-lncRNA2 expression was significantly upregulated in 92%tumor tissues when compared to the adjacent normal tissues(p<0.01);high HUESCC-lncRNA2 group was significantly associated with worse histologic grade,advanced TNM stage,and more lymph node metastasis(p<0.05);decreased overall survival rates(P<0.001),In vitro assays of the ESCC cell lines KYSE30 and TE10 demonstrated that suppression of HUESCC-lncRNA2 expression by si-RNA reduced cell growth and the ability of invasion and migration(all P<0.01).Apoptosis of ESCC cells increased when HUESCC-lncRNA2 expression was suppressed.Conclusions:HUESCC-lncRNA2 is overexpressed in ESCC fresh tissues and cell lines.HUESCC-lncRNA2 expression is well correlated to ESCC progression,aggressive behaviors and poor prognosis.Therefore,we envision that HUESCC-lncRNA2 may be a novel tumor biomarker for diagnose,a prospective prognostic indicator and a potential therapeutic target for ESCC.