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LINC01232 Promotes Gastric Cancer Proliferation through Interacting with EZH2 to Inhibit the Transcription of KLF2

  • Liu, Jing (Department of Pathology, Yantai Yuhuangding Hospital) ;
  • Li, Zhen (Department of General and Pediatric Surgery, Yantai Yuhuangding Hospital) ;
  • Yu, Guohua (Department of Pathology, Yantai Yuhuangding Hospital) ;
  • Wang, Ting (Department of Pathology, Yantai Yuhuangding Hospital) ;
  • Qu, Guimei (Department of Pathology, Yantai Yuhuangding Hospital) ;
  • Wang, Yunhui (Department of General and Pediatric Surgery, Yantai Yuhuangding Hospital)
  • Received : 2021.06.15
  • Accepted : 2021.08.17
  • Published : 2021.10.28

Abstract

To clarify the role of long intergenic nonprotein-coding RNA 1232 (LINC01232) in the progression of gastric cancer and the potential mechanism, we analyzed the expression of LINC01232 in TCGA database using the GEPIA online tool, and the LINC01232 level in gastric cancer cell lines was detected by quantitative real time-polymerase chain reaction (qRT-PCR) as well. Cell proliferation assay, colony formation assay, transwell assay and tumor formation experiment in nude mice were conducted to observe the biological behavior changes of gastric cancer cells through the influence of LINC01232 knockdown. LncATLAS database and subcellular isolation assay were used for subcellular distribution of LINC01232 in gastric cancer cells. The interaction among LINC01232, zeste homolog 2 (EZH2) and kruppel-like factor 2 (KLF2) was clarified by RNA-protein interaction prediction (RPISeq), RNA immunoprecipitation (RIP), qRT-PCR and chromatin immunoprecipitation (ChIP) assay. Rescue experiments were further conducted to elucidate the biological function of LINC01232/KLF2 axis in the progression of gastric cancer. LINC01232 was upregulated in stomach adenocarcinoma (STAD) tissues and gastric cancer lines. LINC01232 knockdown inhibited the proliferative capacities of gastric cancer cells in vitro, and impaired in vivo tumorigenicity. LINC01232 was mainly distributed in the cell nucleus where it epigenetically repressed KLF2 expression via binding to the enhancer of EZH2, which was capable of binding to promoter regions of KLF2 to induce histone H3 lysine 27 trimethylation (H3K27me3). LINC01232 exerts oncogenic activities in gastric cancer via inhibition of KLF2, and therefore, the knockdown of KLF2 could reverse the regulatory effect of LINC01232 in the proliferative ability of gastric cancer cells.

Keywords

References

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