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Long non-coding RNA HOTAIR promotes cell migration by upregulating insulin growth factor-binding protein 2 in renal

Hiromichi Katayama1,2, Keiichi Tamai3, Rie Shibuya1

  • 1Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Natori, Japan.

Scientific Reports
|September 22, 2017
PubMed

Insights

Hox antisense intergenic RNA (HOTAIR) promotes renal cell carcinoma (RCC) metastasis by increasing insulin growth factor-binding protein 2 (IGFBP2) expression. This HOTAIR-IGFBP2 pathway is linked to poor prognosis and may offer a new therapeutic target for advanced RCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Renal cell carcinoma (RCC) is a lethal urologic cancer with high rates of metastasis at diagnosis.
  • Hox antisense intergenic RNA (HOTAIR) is implicated in metastasis in various cancers, but its role in RCC is not fully understood.

Purpose of the Study:

  • To elucidate the mechanism by which HOTAIR contributes to RCC malignancy and metastasis.
  • To investigate the potential of the HOTAIR-IGFBP2 axis as a therapeutic target for advanced RCC.

Main Methods:

  • Correlation analysis of HOTAIR expression with clinical parameters (grade, metastasis, prognosis) in patient datasets.
  • In vitro studies assessing HOTAIR's effect on RCC cell migration and IGFBP2 expression.
  • In vivo studies using immunodeficient mice to evaluate HOTAIR's impact on tumorigenicity and lung metastasis.
  • Microarray analysis to identify genes regulated by HOTAIR.

Main Results:

  • HOTAIR expression positively correlated with higher nuclear grade, lymph-node metastasis, and lung metastasis in RCC patients.
  • High HOTAIR expression predicted poor prognosis in both the study cohort and The Cancer Genome Atlas (TCGA) dataset.
  • HOTAIR overexpression enhanced RCC cell migration and accelerated tumor growth and lung metastasis in mice.
  • HOTAIR upregulates Insulin Growth Factor-Binding Protein 2 (IGFBP2) expression, and HOTAIR-induced migration is dependent on IGFBP2.

Conclusions:

  • The HOTAIR-IGFBP2 axis is a critical driver of metastasis in renal cell carcinoma.
  • HOTAIR and IGFBP2 are co-expressed in clinical RCC samples, highlighting their clinical relevance.
  • Targeting the HOTAIR-IGFBP2 pathway presents a promising therapeutic strategy for advanced RCC.

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