Study On The Mechanism Of Long Non-coding RNA UCA1 Regulating The Proliferation And Metastasis Of Gastric Cancer Cells

One of the most important discoveries from recent studies at the genomic scale is that there are much more abundant non-coding transcripts in different species than previously imagined.Long noncoding RNAs(IncRNAs)are defined as transcripts longer than 200 nt without coding capacities.Compared to short ncRNAs,the functions of lncRNAs are less understood.IncRNAs played a vital role in the regulation of human normal development and differentiation.Dysregulated IncRNAs expression was associated with disease generation and development,including cancer progression.A large number of lncRNAs were expressed disorderly in gastric cancer,and acted as oncogenes or cancer suppressors.In this study,we analyzed the expression levels of UCA1 in human gastric cancer tissues by using raw microarray data downloaded from GEO(Gene Expression Omnibus,GSE53137)and TCGA(The Cancer Genome Atlas).The results showed that the UCA1 expression levels were upregulated in gastric cancerous tissues compared with noncancerous tissues.QRT-PCR was used to testify all above results.UCA1 gene was located in human chromosome 19,and the transcript length was 2314bp.High LUCA1 expression in gastric cancer was significantly correlated with tumor size,advanced TNM stage,lymph node metastasis and patients' prognosis.Knockdown of UCA1 inhibited gastric cancer cell proliferation,metastasis,and promoted cell apoptosis.The result of animal experiment showed that Knockdown of UCA1 suppressed gastric cancer cell tumorigenesis and metastasis in vivo.The results of RNA-seq with GO analysis and KEGG pathway analysis showed that UCA1 regulates proliferation and apoptosis-related gene expression after UCA1 knockdown in gastric cancer cells.QRT-PCR detection further found that SPRY1 and CDKN1A might be UCA1 target genes.Mechanism studies have shown that UCA1 is highly enriched in the nucleus and that UCA1 could bind to Polycomb Repressive Complex 2(PRC2)by RIP experiment.We used ChIP experiment confirmed that UCA1 can affect the SPRY1 and CDKN1A promoter group histone methylation level and thus inhibit the expression of SPRY1 and CDKN1A,thus regulating the proliferation and metastasis of gastric cancer.Furthermore,the results of chromatin immunoprecipitation(ChIP)assays showed that EZH2 could directly bind to SPRY1 and CDKN1A promoter regions and induce the histone H3 lysine 27 trimethylation(H3K27me3).These results suggest that UCA1 could promote gastric cancer cell proliferation and metastasis through epigenetically silencing SPRY1 and CDKN1A transcription by binding to EZH2.All of results showed that UCA1 acted as an oncogene in gastric cancer cell,and participated in gastric cancer malignant progression.UCA1 could be novel biomarkers in gastric cancer diagnosis and prognosis.