Clinical significance and oncogene function of long noncoding RNA HAGLROS overexpression in ovarian cancer

Arch Gynecol Obstet. 2019 Sep;300(3):703-710. doi: 10.1007/s00404-019-05218-5. Epub 2019 Jun 13.

Abstract

Purpose: To explore the clinical significance and mechanism of long noncoding RNA (lncRNA) HAGLROS in ovarian cancer.

Methods: The expression of HAGLROS in ovarian cancer was verified by online databases and quantitative reverse transcription polymerase chain reaction (qRT-PCR), and its relationship with clinicopathological parameters was analysed. Pearson correlation analysis was used to study the correlation between HAGLROS and miR-100 in ovarian cancer. Meta-analysis was used to explore the expression of miR-100 in ovarian cancer. In addition, we used bioinformatics to explore the target genes of miR-100 and perform functional analysis.

Results: HAGLROS was significantly upregulated in ovarian cancer (P < 0.001) and was closely related to disease stage (P = 0.033), tumour size (P = 0.032) and poor prognosis (P = 0.019). HAGLROS had a certain diagnostic value in ovarian cancer (area under the curve = 0.751). MiR-100 was negatively correlated with HAGLROS (r = 0.167, P = 0.001) and significantly downregulated in ovarian cancer. Bioinformatics analysis predicted a total of 31 potential target genes that interact with miR-100. These target genes were mainly involved in the regulation of cellular catabolic process, proteoglycan biosynthetic process and positive regulation of proteasomal ubiquitin-dependent protein catabolic process. Among them, mTOR and ZNRF2 are hub genes.

Conclusion: HAGLROS is a potential biomarker for early diagnosis and prognosis evaluation of ovarian cancer. It can be used as a molecular sponge of miR-100 to regulate the expression of mTOR and ZNRF2 and affect the signal transduction of the mTOR pathway. HAGLROS is expected to be a new target for the treatment of ovarian cancer.

Keywords: HAGLROS; Long noncoding RNA; Ovarian cancer; ZNRF2; mTOR signalling pathway; miR-100.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Ovarian Epithelial / genetics
  • Carcinoma, Ovarian Epithelial / mortality
  • Carcinoma, Ovarian Epithelial / pathology*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • MicroRNAs / genetics*
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology*
  • Prognosis
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism*
  • Ubiquitin-Protein Ligases / metabolism
  • Up-Regulation

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • Ubiquitin-Protein Ligases
  • ZNRF2 protein, human
  • MTOR protein, human
  • TOR Serine-Threonine Kinases