Abstract
Long noncoding RNAs (lncRNAs) play roles in the tumorigenesis, proliferation and metastasis of tumor cells. Previous studies indicate that the transcription factor Sp1 is responsible for transcription of the XIAP gene, but it is unknown whether lncRNAs are involved in XIAP transcription. Herein, we identified a novel lncRNA, denoted as XIAP-AS1, transcribed from the first intron of the complementary strand of the XIAP gene. Using RNA FISH, cell fractionation and qRT-PCR, XIAP-AS1 was determined to be located primarily in the nucleus. After various XIAP-AS1 deletion mutants were expressed, RIP assays showed that only the full-length XIAP-AS1 RNA interacted with Sp1 and thereby participated in XIAP transcription. ChIP assays showed that XIAP-AS1 knockdown decreased the binding of Sp1 to the promoter region of XIAP. XIAP-AS1 knockdown promoted tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in gastric tumor cells, as cleaved caspase-3 and caspase-9 was detected. Moreover, in an in vivo mouse xenograft model, tumor cell proliferation was inhibited by XIAP-AS1 knockdown in response to TRAIL administration. In conclusion, our results indicate that XIAP-AS1 is involved in XIAP transcription by interacting with Sp1. Additionally, XIAP-AS1 is a potential target for TRAIL-induced apoptosis in gastric cancer cells.
Highlights
Long noncoding RNAs are defined as transcripts longer than 200 nucleotides, and they participate in cancer development and metastasis, as well as exert considerable influence on the transcription [1], alternative splicing [2], and translation [3] of target genes
XIAP-AS1 was expressed at various levels in all the gastric cancer cell lines, and XIAP-AS1 expression was positively correlated with XIAP expression (Fig 1B and 1C)
The levels of XIAP-AS1 in stomach adenocarcinoma (n = 285) and normal tissues (n = 33) derived from TCGA were analyzed and the results showed that XIAP-AS1 was highly expressed in stomach adenocarcinoma (S1A Fig)
Summary
Long noncoding RNAs (lncRNAs) are defined as transcripts longer than 200 nucleotides, and they participate in cancer development and metastasis, as well as exert considerable influence on the transcription [1], alternative splicing [2], and translation [3] of target genes. The lncRNA HOTAIR promotes the invasiveness and metastatic potential of human breast cancer cells via recruitment of polycomb repressive complex 2 (PRC2) and induction of H3K27 trimethylation, thereby resulting in altered gene expression [4]. LncRNA MALAT1 is involved in the alternative splicing of target genes by the recruitment of serine/arginine-rich splicing factor 1 (SRSF1) [2]. Et al report that lincRNA-p21 selectively lowers the translation of target gene CTNNB1 and JUNB mRNA by its partial complement with target. JH. et al report that lincRNA-p21 selectively lowers the translation of target gene CTNNB1 and JUNB mRNA by its partial complement with target
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