The lncRNA UCA1 promotes proliferation, migration, immune escape and inhibits apoptosis in gastric cancer by sponging anti-tumor miRNAs

Abstract

Background 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, however, the role of UCA1 during the processes of immune escape is still not unclear. Methods We 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. Results UCA1 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. Conclusions UCA1 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. Electronic supplementary material The online version of this article (10.1186/s12943-019-1032-0) contains supplementary material, which is available to authorized users.

LINC00673 is activated by YY1 and promotes the proliferation of breast cancer cells via the miR-515-5p/MARK4/Hippo signaling pathway

“…Most of the lncRNAs that have been investigated thus far act in the nucleus by regulating gene expression [40]. However, lncRNAs also act as ceRNAs to regulate mRNA degradation and translation in the cytoplasm [41]. Thus, we first assessed the cellular localization of LINC00673 by measuring its expression in the nucleus and cytoplasm in MDA-MB-453 and MDA-MB-231 cells.…”

Long Non-coding RNAs: Emerging Roles in the Immunosuppressive Tumor Microenvironment

“…LncRNAs can indirectly upregulate PD-L1 expression by sponging miRNAs. For example, lncRNA UCA1 repressed the expression of miR-193a, miR-26a/b, and miR-214 in gastric cancer through direct interactions and improved the expression of PD-L1 (58).…”

Silencing of long noncoding RNA UCA1 inhibits colon cancer invasion, migration and epithelial‐mesenchymal transition and tumour formation by upregulating miR‐185‐5p in vitro and in vivo

“…As an oncogene, UCA1 promoted the growth and motility of laryngeal squamous cell carcinoma cells by activating the Wnt/β‐catenin pathway . Wang et al found that UCA1 participated in immune escape and metastasis of gastric cancer cells by binding to miR‐26a/b, miR‐193a and miR‐214 and reversing the inhibitory effect of miRNAs on PDL1 expression . Chen et al pointed out that UCA1 regulated Wnt/β‐catenin signalling pathway by competitively adsorbing miR‐185‐5p, thereby inhibiting the invasion of melanoma cells and EMT .…”