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LncRNA HSP90AA1-IT1 promotes gliomas by targeting miR-885-5p-CDK2 pathway

Taihong Gao1, Guangyan Gu2, Jingxia Tian3

  • 1Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China.

Oncotarget
|November 2, 2017
PubMed

Insights

The long noncoding RNA HSP90AA1-IT1 promotes glioma development by inhibiting miR-885-5p, which targets CDK2. This lncRNA is a potential therapeutic target for glioma treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Non-coding RNAs (ncRNAs) are increasingly recognized as crucial regulators in cancer, but their specific roles in gliomagenesis require further elucidation.
  • The long noncoding RNA (lncRNA) HSP90AA1-intronic transcript 1 (HSP90AA1-IT1) has emerged as a potential player in cancer, with its expression levels and functional significance in gliomas not yet fully understood.

Purpose of the Study:

  • To investigate the role of HSP90AA1-IT1 in glioma progression and its underlying molecular mechanisms.
  • To determine the correlation between HSP90AA1-IT1 expression and glioma pathological grades and patient prognosis.
  • To identify potential therapeutic targets for glioma treatment based on HSP90AA1-IT1's function.

Main Methods:

  • Quantitative real-time PCR to assess HSP90AA1-IT1 expression levels in glioma tissues and cell lines.
  • Cell viability, proliferation, apoptosis, cell cycle, epithelial-mesenchymal transition (EMT), invasion, and migration assays in glioma cell lines with altered HSP90AA1-IT1 expression.
  • In vivo tumor formation assays in nude mice.
  • RNA immunoprecipitation (RIP) and dual-luciferase reporter assays to confirm the direct binding of HSP90AA1-IT1 to miR-885-5p and its interaction with CDK2.

Main Results:

  • HSP90AA1-IT1 expression levels correlated with glioma pathological grades, and high expression predicted poor prognosis.
  • Downregulation of HSP90AA1-IT1 significantly suppressed glioma cell viability, proliferation, EMT, invasion, and migration, while increasing apoptosis and altering cell cycle progression.
  • Reduced tumorigenic capacity was observed in vivo upon HSP90AA1-IT1 downregulation.
  • HSP90AA1-IT1 directly binds to miR-885-5p and competitively inhibits miR-885-5p-mediated repression of CDK2, a key regulator in gliomagenesis.

Conclusions:

  • HSP90AA1-IT1 acts as an oncogenic lncRNA in glioma development by regulating the miR-885-5p-CDK2 signaling axis.
  • HSP90AA1-IT1's role in tumorigenesis provides a novel perspective and suggests its potential as a therapeutic target for glioma treatment.
Keywords:
CDK2HSP90AA1-IT1gliomalncRNAmiR-885-5p

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