Abstract. Long non-coding RNAs (lncRNAs) have been recognized as a regulator of gene expression, and the deregulation of lncRNAs have been reported to be correlated with carcinogenesis and cancer progression. To explore the function of lncRNA in endometrial carcinoma, we analyzed the expression profiles of lncRNAs and coding genes in 3 paired endometrial carcinoma and adjacent non-tumor tissues, using a microarray. The results of microarray analysis indicated a significant difference in lncRNA and coding gene expression between endometrial carcinoma and their paired adjacent nontumor tissues. A total of 53 lncRNAs (fold change >2.0, p-value <0.05) were found to be differently expressed in endometrial carcinoma compared to the normal controls. Among these ASLNC04080 was the most significantly upregulated lncRNA in microarray data, highly expressed in 22 out of 24 endometrial carcinoma tissues and HEC-1-B cell line. ASLNC04080 is 1867nt in length, consist of 6 exons, and locates at 1 p35.3(chr1: -28905061 --28909492). In addition, 46 coding gene transcripts were differentially expressed (fold change >2.0, p-value <0.05) between endometrial carcinoma and adjacent non-tumor tissues. Pathway and gene ontology analysis demonstrated that these deregulated transcripts were involved in multiple signal pathways, biological processes, cellular components and molecular functions. Moreover, the ASLNC04080 lncRNA expression was correlated with 19 coding genes, and may contribute to endometrial carcinoma genesis and progression by co-regulating with coding gene. Expression inhibition of lncRNA ASLNC04080 in HEC-1-B cells caused repression of cell proliferation, increased cell apoptosis, and G1 phase arrest. These results suggested a potential function of ASLNC04080 in endometrial carcinoma genesis and progression.
IntroductionEndometrial carcinoma, comprising of several types of malignancies arise from the endometrium or lining of the uterus, is the most common gynecologic malignancy among women in the United States, with an estimated 52,630 new case and 8,590 deaths in 2014 (1). Endometrial carcinoma cases in Chinese women increased in the last decade. Based on clinical features and pathogenesis endometrial carcinomas have been classified into two types (2). Type I endometrial carcinomas occur commonly in perimenopausal women, with low grade, related to obesity and estrogen exposure. Type II endometrial carcinomas are more common in older women, unrelated to hormone excess, with a worse outcome than Type I. Previous studies have reported that various gene mutations, and expression deregulation are related to endometrial carcinoma genesis. PTEN and K-ras mutations occur in Type I endometrial carcinomas, often with Wnt, AKT and PI3KCA deregulation. TP53 and PPP2R1A mutations are frequent in Type II endometrial carcinomas, with HER2/neu overexpression and p16 inactivation (3,4).LncRNAs are a spectrum of RNAs transcripted by RNA polymerase II, but not translated into proteins, with more than 200 nucleotides in length. LncRNAs whi...