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Long non-coding RNA HOTAIR promotes cell migration by upregulating insulin growth factor-binding protein 2 in renal cell carcinoma
Open accessAbstract
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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IGFBP2 is the most up-regulated gene in cEDS cells.
“IGFBP2 (insulin-like growth factor-binding protein 2), the most up-regulated gene in cEDS cells, enhances cell migration in different cell types through its binding to αvβ3 and α5β1 integrins [72,73].”
From Cellular and Molecular Mechanisms in the Pathogenesis of Classical, Vascular, and Hypermobile Ehlers‒Danlos Syndromes (2019) · cites this paper as [73]
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References 42 · Cited by 37
Metadata
- Authors
- Katayama, H., Tamai, K., Shibuya, R., Nakamura, M., Mochizuki, M., Yamaguchi, K., Kawamura, S., Tochigi, T., Sato, I., Okanishi, T., Sakurai, K., Fujibuchi, W., Arai, Y., & Satoh, K.
- Affiliations
- Tohoku University (JP)
- Miyagi Prefectural Hospital Organization (JP)
- Kyoto University (JP)
- Corresponding author
- Tamai, Keiichi
- ORCID
- Venue
- Scientific Reports
- Published
- 2017-09-20
- Volume
- 7
- Issue
- 1
- Pages
- 12016-12016
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5607269
- OpenAlex
- W2754087347
- Cited by
- 37
- References
- 42
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 8 · 2021: 4 · 2020: 1 · 2019: 10 · 2018: 3
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion, cc-by)
- Funders
- Japan Agency for Medical Research and Development
- Novartis Pharma
- Japan Society for the Promotion of Science (16K07187, 16K20290, 17H06396, 16K07132, 15K06848, 15K09055)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Health Sciences › Medicine › Oncology › Renal cell carcinoma treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Keywords
- HOTAIR, long non-coding RNA, renal cell carcinoma, IGFBP-2, cell migration, metastasis, lung metastasis, prognostic factors, therapeutic target
- MeSH terms
- Animals, Carcinoma, Renal Cell, Cell Movement, Female, Humans, Kidney Neoplasms, Lung Neoplasms, Lymphatic Metastasis, Male, Middle Aged, Transplantation, Heterologous, Up-Regulation, Gene Expression Regulation, Neoplastic, Mice, SCID, Mice, Inbred NOD, Mice, Knockout, Insulin-Like Growth Factor Binding Protein 2, Gene Expression Profiling, RNA Interference, Cell Line, Tumor, Kaplan-Meier Estimate, RNA, Long Noncoding
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