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Updated: Nov 19, 2025

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Long Noncoding RNA HOXA11-AS and Transcription Factor HOXB13 Modulate the Expression of Bone Metastasis-Related Genes
Aya Misawa1, Yukihiro Kondo2, Hiroyuki Takei3
1Department of Molecular Medicine and Anatomy, Nippon Medical School, 1-1-5 Sendagi, Tokyo 113-8602, Japan.
Abstract:
Long noncoding RNAs (lncRNAs) are emerging as critical regulators of gene expression, which play fundamental roles in cancer development. In this study, we found that homeobox A11 antisense RNA (HOXA11-AS), a highly expressed lncRNA in cell lines derived from prostate cancer bone metastases, promoted the cell invasion and proliferation of PC3 prostate cancer cells. Transcription factor homeobox B13 (HOXB13) was identified as an upstream regulator of HOXA11-AS.HOXA11-AS regulated bone metastasis-associated C-C motif chemokine ligand 2 (CCL2)/C-C chemokine receptor type 2 (CCR2) signaling in both PC3 prostate cancer cells and SaOS2 osteoblastic cells. The HOXB13/HOXA11-AS axis also regulated integrin subunits (ITGAV and ITGB1) specific to prostate cancer bone metastasis. HOXB13, in combination with HOXA11-AS, directly regulated the integrin-binding sialoprotein (IBSP) promoter. Furthermore, conditioned medium containing HOXA11-AS secreted from PC3 cells could induce the expression of CCL2 and IBSP in SaOS2 osteoblastic cells. These results suggest that prostate cancer HOXA11-AS and HOXB13 promote metastasis by regulation of CCL2/CCR2 cytokine and integrin signaling in autocrine and paracrine manners.
Insights
Prostate cancer metastasis is promoted by the HOXA11-AS long noncoding RNA and HOXB13 transcription factor. They regulate key signaling pathways involved in bone metastasis, offering potential therapeutic targets.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Long noncoding RNAs (lncRNAs) are critical regulators of gene expression with roles in cancer development.
- Prostate cancer bone metastasis involves complex molecular signaling pathways.
Purpose of the Study:
- To investigate the role of HOXA11-AS in prostate cancer bone metastasis.
- To identify upstream regulators and downstream targets of HOXA11-AS in this context.
Main Methods:
- Analysis of HOXA11-AS expression in prostate cancer bone metastasis cell lines.
- Investigating the effects of HOXA11-AS on PC3 cell invasion and proliferation.
- Identifying HOXB13 as an upstream regulator.
- Studying the regulation of CCL2/CCR2, ITGAV, ITGB1, and IBSP signaling.
- Assessing the effects of secreted HOXA11-AS on osteoblastic cells.
Main Results:
- HOXA11-AS is highly expressed in prostate cancer bone metastasis cell lines and promotes PC3 cell invasion and proliferation.
- HOXB13 acts as an upstream regulator of HOXA11-AS.
- The HOXB13/HOXA11-AS axis regulates CCL2/CCR2, ITGAV, ITGB1, and IBSP signaling.
- Secreted HOXA11-AS from PC3 cells induces CCL2 and IBSP expression in SaOS2 osteoblastic cells.
Conclusions:
- Prostate cancer HOXA11-AS and HOXB13 promote metastasis.
- They regulate metastasis through autocrine and paracrine actions on cytokine and integrin signaling pathways.
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