Long Non-coding RNA HOTAIR Promotes Cell Migration by Upregulating Insulin Growth Factor-binding Protein 2 in Renal Cell Carcinoma

Overview

Journal Sci Rep

Specialty Science

Date 2017 Sep 22

PMID 28931862

Citations 18

Authors

Hiromichi Katayama

Keiichi Tamai

Rie Shibuya

Mao Nakamura

Mai Mochizuki

Kazunori Yamaguchi

Sadafumi Kawamura

Tatsuo Tochigi

Ikuro Sato

Takamasa Okanishi

Kunie Sakurai

Wataru Fujibuchi

Yoichi Arai

Kennichi Satoh

Affiliations

Soon will be listed here.

Abstract

Renal cell carcinoma (RCC) is one of the most lethal urologic cancers. About one-third of RCC patients already have distal metastasis at the time of diagnosis. There is growing evidence that Hox antisense intergenic RNA (HOTAIR) plays essential roles in metastasis in several types of cancers. However, the precise mechanism by which HOTAIR enhances malignancy remains unclear, especially in RCC. Here, we demonstrated that HOTAIR enhances RCC-cell migration by regulating the insulin growth factor-binding protein 2 (IGFBP2) expression. HOTAIR expression in tumors was significantly correlated with nuclear grade, lymph-node metastasis, and lung metastasis. High HOTAIR expression was associated with a poor prognosis in both our dataset and The Cancer Genome Atlas dataset. Migratory capacity was enhanced in RCC cell lines in a HOTAIR-dependent manner. HOTAIR overexpression accelerated tumorigenicity and lung metastasis in immunodeficient mice. Microarray analysis revealed that IGFBP2 expression was upregulated in HOTAIR-overexpressing cells compared with control cells. The enhanced migration activity of HOTAIR-overexpressing cells was attenuated by IGFBP2 knockdown. IGFBP2 and HOTAIR were co-expressed in clinical RCC samples. Our findings suggest that the HOTAIR-IGFBP2 axis plays critical roles in RCC metastasis and may serve as a novel therapeutic target for advanced RCC.

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