Long-Noncoding RNA Colorectal Neoplasia Differentially Expressed Gene as a Potential Target to Upregulate the Expression of IRX5 by miR-136-5P to Promote Oncogenic Properties in Hepatocellular Carcinoma

Cell Physiol Biochem. 2018;50(6):2229-2248. doi: 10.1159/000495084. Epub 2018 Nov 13.

Abstract

Background/aims: The long-noncoding RNA colorectal neoplasia differentially expressed (CRNDE) gene was first found to be activated in colorectal neoplasia. Now, it also has been found to be upregulated in many other solid tumors. Whether CRNDE affects tumorigenesis remains unknown.

Methods: We conducted bioinformatics, real-time polymerase chain reaction (PCR), Western blot analysis, cell proliferation assay, colony formation assay, wound healing assay, cell migration and invasion assays, RNA immunoprecipitation, and reporter vector construction and luciferase assays.

Results: CRNDE was upregulated in hepatocellular carcinoma (HCC). The overexpression of CRNDE promoted HCC cellular proliferation, migration, and invasion in intro and in vivo, and acted as an oncogene in HCC progression. Furthermore, CRNDE impaired miR-136-5P expression in a RISC manner, and a reciprocal repression feedback loop was possible between CRNDE and miR-136-5P. We found that the neighboring mRNA of CRNDE was IRX5, and IRX5 increased the tumorigenicity of HCC cells. IRX5 was a potential downstream target gene of miR-136-5P. MiR-136 regulated IRX5 by interacting with its 3'UTR. In addition, miR-136-5P was involved in the CRNDE-regulated expression of IRX5.

Conclusion: CRNDE acted as a tumor oncogene by exhibiting oncogenic properties of human HCC and revealed a novel CRNDE-miR-136-5P-IRX5 regulatory network in HCC. CRNDE may be considered to be a potential target for HCC therapies based on its ability to upregulate IRX5, and it deserves further investigation.

Keywords: CRNDE; HCC; IRX5; Oncogenic property; miR-136-5P.

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Antagomirs / metabolism
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Homeodomain Proteins / chemistry
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Metastasis
  • RNA Interference
  • RNA, Long Noncoding / antagonists & inhibitors
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Small Interfering / metabolism
  • RNA, Small Interfering / therapeutic use
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Up-Regulation

Substances

  • 3' Untranslated Regions
  • Antagomirs
  • CRNDE RNA, human
  • Homeodomain Proteins
  • IRX5 protein, human
  • MIRN136 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • Transcription Factors