MicroRNA-29b regulates migration in oral squamous cell carcinoma and its clinical significance
Journal
Oral Oncology
Journal Volume
51
Journal Issue
2
Pages
170-177
Date Issued
2015
Author(s)
Yang C.-N.
Tang J.-Y.
Chen S.-T.
Li Y.-J.
Wu T.-S.
Yang M.-H.
Chang C.-C.
Abstract
Objectives: MicroRNA (miRNA) machinery regulates cancer cell behavior, and has been implicated in patients' clinical status and prognosis. We found that microRNA-29b (miR-29b) increased significantly in advanced migratory cells. However, miR-29b controls the migration ability, and its regulatory mechanism in oral squamous cell carcinoma (OSCC) remains unknown. Materials and methods: We triggered miR-29b expression in OSCC patients and cell lines by conducting real-time quantitative PCR. We determined the functions of miR-29b in the migration of OSCC cells by using gain- and loss-of-function approaches. We elevated the target genes of miR29b through software predictions and a luciferase report assay. We used an orthotopic OSCC animal model to investigate the effects of miR29b on OSCC cell metastasis in vivo. Results: The clinical data revealed that miR-29b expression was correlated with lymph node metastasis and an advanced tumor stage in 98 OSCC patients. Furthermore, multivariate analysis revealed that miR-29b expression was significantly correlated with recurrence, and indicated poor survival. MiR-29b promoted OSCC cell migration and downregulated CX3CL1, a cell-cell adhesion regulator, which plays an essential role in miR-29b-regulated OSCC cell migration machinery. Furthermore, we found that CX3CL1 expression was correlated with lymph node metastasis and an early tumor stage in OSCC patients, and negatively correlated with miR-29b expression. Conclusion: MiR-29b acts as an oncomir, promoting cell migration through CX3CL1 suppression, and could be a potential therapeutic target for preventing OSCC progression. ? 2014 Elsevier Ltd. All rights reserved.
Other Subjects
fractalkine; microRNA 29b; fractalkine; microRNA; MIRN29 microRNA, human; advanced cancer; Article; cancer patient; cancer prognosis; cancer recurrence; cancer staging; cancer survival; cell function; cell migration; controlled study; down regulation; gain of function mutation; gene expression; human; human cell; in vivo study; loss of function mutation; luciferase assay; lymph node metastasis; mouth squamous cell carcinoma; oral cancer cell line; priority journal; quantitative analysis; real time polymerase chain reaction; regulatory mechanism; animal; gene silencing; genetics; lymph node metastasis; metastasis; mouse; mouth tumor; pathology; physiology; squamous cell carcinoma; survival; Animals; Carcinoma, Squamous Cell; Chemokine CX3CL1; Gene Silencing; Humans; Lymphatic Metastasis; Mice; MicroRNAs; Mouth Neoplasms; Neoplasm Metastasis; Survival Analysis
Publisher
Elsevier Ltd
Type
journal article