Loss of HOXD10 expression induced by upregulation of miR-10b accelerates the migration and invasion activities of ovarian cancer cells

Nakayama,Ikue; Shibazaki,Masahiko; Yashima-Abo,Akiko; Miura,Fumiharu; Sugiyama,Toru; Masuda,Tomoyuki; Maesawa,Chihaya

doi:10.3892/ijo.2013.1935

Loss of HOXD10 expression induced by upregulation of miR-10b accelerates the migration and invasion activities of ovarian cancer cells

Authors:
- Ikue Nakayama
- Masahiko Shibazaki
- Akiko Yashima-Abo
- Fumiharu Miura
- Toru Sugiyama
- Tomoyuki Masuda
- Chihaya Maesawa
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Affiliations: Department of Tumor Biology, Institute of Biomedical Science, Iwate Medical University, Iwate, Japan, Department of Pathology, School of Medicine, Iwate Medical University, Iwate, Japan, Department of Obstetrics and Gynecology, School of Medicine, Iwate Medical University, Iwate, Japan
Published online on: May 13, 2013 https://doi.org/10.3892/ijo.2013.1935
Pages: 63-71

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Abstract

Small and large non-coding RNAs (ncRNAs) contribute to the acquisition of aggressive tumor behavior in diverse human malignancies. Two types of ncRNAs, miRNA‑10b (miR-10b) and homemobox (HOX) transcript antisense RNA (HOTAIR), can suppress the translation of the HOXD10 gene, an mRNA encoding a transcriptional repressor that inhibits the expression of cell migration/invasion-associated genes. Using epithelial ovarian cancer cell lines and primary tumors, we investigated whether miR‑10b and/or HOTAIR can regulate the expression of HOXD10, and whether it permits gain of pro‑metastatic gene products, matrix metallopeptidase 14 (MMP14) and ras homolog family member C (RHOC). Overexpression of miR-10b induced a decrease in HOXD10 protein expression, and upregulated the migration and invasion abilities in ovarian cancer cell lines (P<0.05). In these cells, a significant increase of MMP14 and RHOC protein was observed. No significant upregulation of the HOXD10 protein was observed in cells with the treatment of HOTAIR-siRNA. Positive signals for HOXD10 and MMP14 proteins were observed in 47 (69%) and 25 (37%) of 68 patients with epithelial ovarian cancers. An inverse correlation between HOXD10 and MMP14 immunoreactivities was observed (P<0.05), and miR-10b expression was also inversely correlated with HOXD10 protein expression (P<0.05). These results suggested that downregulation of HOXD10 expression by miR-10b overexpression may induce an increase of pro-metastatic gene products, such as MMP14 and RHOC, and contribute to the acquisition of metastatic phenotypes in epithelial ovarian cancer cells.

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