Abstract
BackgroundUCA1 is a long non-coding RNA which was found overexpressed in various human cancers including gastric cancer (GC). It is identified that UCA1 promotes GC cells proliferation, migration and invasion, however, the role of UCA1 during the processes of immune escape is still not unclear.MethodsWe collected 40 paired GC and non-tumor tissue samples. The level of UCA1 in GC and control tissue samples were determined by in situ hybridization and qRT-PCR. Cell viability was determined by MTT assay. GC cells’ migration capacities were examined by transwell assay. To understand the roles of UCA1 during immune escape, wildtype or UCA1 KO GC cells co-cultured with peripheral blood mononuclear cells or cytokine-induced killer cells in vitro. Mouse model was used to examine the function of UCA1 in vivo.ResultsUCA1 promoted GC cells proliferation and migration, and inhibit apoptosis. UCA1 repressed miR-26a/b, miR-193a and miR-214 expression through direct interaction and then up-regulated the expression of PDL1. UCA1-KO GC cells could induce a higher IFNγ expression when co-cultured with peripheral blood mononuclear cells (PBMCs), and have a lower survival rate when co-cultured with cytokine-induced killer (CIK) cells in vitro. UCA1-KO GC cells formed smaller tumors, had higher miR-26a, −26b, −193a and − 214 level, reduced cell proliferation and increased apoptosis in xenograft mouse model.ConclusionsUCA1 overexpression protected PDL1 expression from the repression of miRNAs and contributed to the GC cells immune escape. UCA1 could serve as a potential novel therapeutic target for GC treatment.
Highlights
As the fourth most common cancer worldwide, gastric cancer (GC) is still incurable and induces about 700, 000 mortalities each year [1,2,3,4]
To further confirm up-regulation of UCA1 in GC tissues and identify its subcellular location, we detected the UCA1 in GC and control tissue sections using in situ hybridization (ISH)
We found miR-26a and -b may bind with UCA1 directly, and this binding was subsequently confirmed by dualluciferase assay (Fig. 3a, b), RNA antisense purification (RAP) assay (Additional file 3: Figure S3A) and Fluorescence in situ hybridization (FISH) (Additional file 3: Figure S3B)
Summary
As the fourth most common cancer worldwide, gastric cancer (GC) is still incurable and induces about 700, 000 mortalities each year [1,2,3,4]. Among the newly discovered RNA elements, long non-coding RNAs (lncRNAs) have been identified to function as key regulators of diverse cellular processes, such as development, differentiation, and cell fate as well as disease pathogenesis [8, 9]. LncRNAs can serve as signal mediators, molecular decoys and scaffold or enhancers of transcription and what is intriguing is that a large group of lncRNAs function as competing endogenous. Different groups have screened the expression profile of lncRNAs in GC tumors and found several disordered lncRNAs relates to GC carcinogenesis such as PVT1, H19, LNC00152 and so on [11,12,13]. UCA1 is a long non-coding RNA which was found overexpressed in various human cancers including gastric cancer (GC). It is identified that UCA1 promotes GC cells proliferation, migration and invasion, the role of UCA1 during the processes of immune escape is still not unclear
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