The long noncoding RNA XIAP-AS1 promotes XIAP transcription by XIAP-AS1 interacting with Sp1 in gastric cancer cells

PLoS One. 2017 Aug 8;12(8):e0182433. doi: 10.1371/journal.pone.0182433. eCollection 2017.

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.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Carcinogenesis / metabolism
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Nucleus / pathology
  • Cell Proliferation / physiology
  • Cytoplasm / metabolism
  • Cytoplasm / pathology
  • Female
  • Gene Expression Regulation, Neoplastic / physiology
  • Gene Knockdown Techniques
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Transplantation
  • Promoter Regions, Genetic
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Sp1 Transcription Factor / metabolism*
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • TNF-Related Apoptosis-Inducing Ligand / metabolism
  • X-Linked Inhibitor of Apoptosis Protein / metabolism

Substances

  • RNA, Long Noncoding
  • Sp1 Transcription Factor
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • X-Linked Inhibitor of Apoptosis Protein
  • XIAP protein, human
  • long noncoding RNA XIAP-AS1, human

Grants and funding

This research was supported by grants from Basic-Clinical research cooperation fund of Beijing Friendship Hospital Affiliated to Capital Medical University (14JL33).