miR-2682-3p antagonizes its host lncRNA-MIR137HG by interacting with the same target FUS to regulate the progression of gastric cancer

BMC Cancer. 2022 Jun 22;22(1):689. doi: 10.1186/s12885-022-09740-9.

Abstract

Background: The mechanism of long non-coding RNA MIR137HG in human gastric cancer (GC) is currently unknown. In the present study, we aimed to explore the function and mechanism of MIR137HG in gastric cancer.

Methods: The expression of lncRNA-MIR137HG in 69 gastric cancer samples and their paired surgical margin (SM) tissue samples were tested by QRT-PCR. UCSC was used to find the gene location relationship among MIR137HG and its embedded miRNAs. TargetScan was used to predict the targets of miR-2682-3p. Starbase was used to predict the candidate proteins that interacted with MIR137HG. Western blot, co-focus, and RIP assay were used to verify the direct interaction between MIR137HG and FUS (fused in sarcoma/translocated in liposarcoma, FUS/TLS), while dual-luciferase reporter assay was used to confirm the interaction between miR-2682-3p and FUS. Cell migration assays, colony formation, and xenografts assay were used to investigate the function of MIR137HG and miR-2682-3p to tumor growth and metastasis. Western blot assay was used to explore the downstream candidate protein of FUS.

Results: Data showed that MIR137HG expressed significantly higher in GC than in SM. MIR137HG promoted colony formation and migration in vitro and promoted tumor formation and metastasis in vivo. MIR137HG is distributed in both the nucleus and cytoplasm. It was co-located with FUS and could directly interact with FUS, which might interact with other proteins, such as MET(MET-proto-oncogene, receptor tyrosine kinase), RHOC(ras homolog family member), and CTNNB1(catenin beta1). These proteins may involve different signaling pathways to regulate gastric cancer progression. By contrast, the embedded miR-2682-3p could antagonize the series functions of its host lncRNA-MIR137HG by targeting FUS.

Conclusions: lncRNA-MIR137HG promoted growth and metastasis in gastric cancer by interacting with FUS, while miR-2682-3p could inhibit the function of MIR137HG via the same target FUS.

Keywords: FUS; Gastric cancer; LncRNA; MIR137HG; miR-2682-3p.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • RNA-Binding Protein FUS* / genetics
  • RNA-Binding Protein FUS* / metabolism
  • Stomach Neoplasms* / pathology

Substances

  • FUS protein, human
  • MIRN137 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA-Binding Protein FUS