MYC-activated lncRNA HNF1A-AS1 overexpression facilitates glioma progression via cooperating with miR-32-5p/SOX4 axis

Cancer Med. 2020 Sep;9(17):6387-6398. doi: 10.1002/cam4.3186. Epub 2020 Jul 20.

Abstract

Mounting literatures have revealed the crucial effects of long noncoding RNA (lncRNA) in various cancers, including glioma. HNF1A-AS1, a novel lncRNA, is reported to modulate tumorigenesis and development of multiple cancers. However, the tumorigenic function of lncRNA HNF1A-AS1 in glioma remains largely unknown. quantitative reverse transcription and polymerase chain reaction and western blot assays were applied to evaluate the expression of relevant mRNAs and proteins. 5-Ethynyl-2'- deoxyuridine, terminal deoxynucleotidyl transferase dUTP nick-end labeling, flow cytometry, and transwell assays were conducted for examining the influence of HNF1A-AS1 on glioma cell functions. The relationship among RNAs was investigated by mechanical experiments. The results demonstrated that HNF1A-AS1 was predominantly highly expressed in glioma cell lines compared with nontumor glial epithelial cell, which was associated with the stimulation of transcription factor myelocytomatosis oncogene. Knockdown of HNF1A-AS1 remarkably inhibited glioma cells proliferation, migration, and invasion, while accelerating cell apoptosis in vitro. Mechanically, HNF1A-AS1 served as a miR-32-5p sponge. Moreover, SOX4 was discovered as a target of miR-32-5p. Inhibited miR-32-5p or upregulated SOX4 could markedly counteract the inhibitory effects of silencing HNF1A-AS1 on glioma malignant biological behaviors. HNF1A-AS1 exerted oncogenic property in glioma progression via upregulating miR-32-5p-mediated SOX4 expression, suggesting potential novel therapeutic target for future glioma treatment.

Keywords: HNF1A‐AS1; SOX4; miR‐32‐5p; glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Brain Neoplasms / etiology
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • DNA Nucleotidylexotransferase
  • Deoxyuridine / analogs & derivatives
  • Disease Progression
  • Flow Cytometry
  • Gene Silencing
  • Glioma / etiology
  • Glioma / metabolism*
  • Glioma / pathology
  • Humans
  • In Situ Nick-End Labeling
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Neoplasm Proteins / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • SOXC Transcription Factors / metabolism*
  • Transcription Factors / metabolism

Substances

  • MIRN32 microRNA, human
  • MYC protein, human
  • MicroRNAs
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-myc
  • RNA, Long Noncoding
  • SOX4 protein, human
  • SOXC Transcription Factors
  • Transcription Factors
  • long non-coding RNA HNF1A-AS1, human
  • DNA Nucleotidylexotransferase
  • 5-ethynyl-2'-deoxyuridine
  • Deoxyuridine