Cheng-Ning Yang1, Yi-Ting Deng2, Jia-Yu Tang3, Shih-Jung Cheng4, Szu-Ta Chen5, Yue-Ju Li6, Tai-Sheng Wu6, Muh-Hwa Yang7, Been-Ren Lin8, Mark Yen-Ping Kuo9, Jenq-Yuh Ko10, Cheng-Chi Chang11. 1. Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan. 2. Department of Dentistry, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan. 3. Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan. 4. Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan. 5. Department of Pediatrics, National Taiwan University Hospital Yun-Lin Branch, Yunlin, Taiwan; Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan. 6. Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan. 7. Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan. 8. Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan. 9. Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan. 10. Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan. 11. Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan; Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan; Angiogenesis Research Center, National Taiwan University, Taipei, Taiwan. Electronic address: ccclrc@gmail.com.
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.
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.
Authors: Christopher A Drummond; Michael C Hill; Huilin Shi; Xiaoming Fan; Jeffrey X Xie; Steven T Haller; David J Kennedy; Jiang Liu; Michael R Garrett; Zijian Xie; Christopher J Cooper; Joseph I Shapiro; Jiang Tian Journal: Physiol Genomics Date: 2015-12-23 Impact factor: 3.107
Authors: Gerhard Schmalz; Simin Li; Ralph Burkhardt; Sven Rinke; Felix Krause; Rainer Haak; Dirk Ziebolz Journal: Biomed Res Int Date: 2016-06-27 Impact factor: 3.411