Kunliang Luo1, Jun He1, Dongqin Yu2, Yahya Açil3. 1. Department of Dentistry, Sir Run Run Shaw Hospital, Affiliated with The Zhejiang University School of Medicine Hangzhou, Zhejiang, China. 2. Department of Stomatology, Shaoxing Central Hospital Shaoxing, Zhejiang, China. 3. Department of Oral and Maxillofacial Surgery, University Hospital of Schleswig-Holstein Campus Kiel, Arnold-Heller-Straße 3, 24105 Kiel, Germany.
Abstract
BACKGROUND: Oral squamous cell carcinoma (OSCC) is a public health problem worldwide. MicroRNAs, acting as either oncogenes or tumor suppressors, have gathered much attention. The aim of this study was to characterize the role of miR-149-5p in drug resistance, cell growth, and metastasis and its underlying mechanism in oral squamous cell carcinoma. METHODS: The expressions of miR-149-5p and TGFβ2 were measured by quantitative real-time polymerase chain reaction. The survival rate of cells treated with different concentrations of CDDP was checked by CCK-8. The cell proliferation and apoptosis was determined by CCK-8 and flow cytometry, respectively. Cell migration and invasion were examined using transwell assay. The interaction of miR-149-5p and TGFβ2 was predicted by online software Targetscan and confirmed by luciferase reporter assay. The protein expression of TGFβ2, p-SMAD2 and p-SMAD3 was quantified using western blot. RESULTS: The expression of miR-149-5p was obviously decreased in OSCC tissues and cell lines, and its expression was lower in a cisplatin resistant cell line (CAL-27/CDDP) than that of a normal OSCC cell line (CAL-27). CCK-8 assay suggested that miR-149-5p increased drug sensitivity in CAL-27 and CAL-27/CDDP cells. miR-149-5p attenuated proliferation, migration and invasion, and promoted apoptosis of CAL-27 and CAL-27/CDDP cells. In addition, TGFβ2 was up-regulated in OSCC cells at both mRNA and protein levels. Moreover, miR-149-5p promoted cisplatin chemosensitivity and regulated cell proliferation, apoptosis, migration and invasion by targeting TGFβ2 in CAL-27 and CAL-27/CDDP cells. CONCLUSION: miR-149-5p regulates cisplatin chemosensitivity, cell growth, apoptosis and metastasis by targeting TGFβ2. miR-149-5p/TGFβ2 axis has potential for therapy of OSCC. IJCEP
BACKGROUND:Oral squamous cell carcinoma (OSCC) is a public health problem worldwide. MicroRNAs, acting as either oncogenes or tumor suppressors, have gathered much attention. The aim of this study was to characterize the role of miR-149-5p in drug resistance, cell growth, and metastasis and its underlying mechanism in oral squamous cell carcinoma. METHODS: The expressions of miR-149-5p and TGFβ2 were measured by quantitative real-time polymerase chain reaction. The survival rate of cells treated with different concentrations of CDDP was checked by CCK-8. The cell proliferation and apoptosis was determined by CCK-8 and flow cytometry, respectively. Cell migration and invasion were examined using transwell assay. The interaction of miR-149-5p and TGFβ2 was predicted by online software Targetscan and confirmed by luciferase reporter assay. The protein expression of TGFβ2, p-SMAD2 and p-SMAD3 was quantified using western blot. RESULTS: The expression of miR-149-5p was obviously decreased in OSCC tissues and cell lines, and its expression was lower in a cisplatin resistant cell line (CAL-27/CDDP) than that of a normal OSCC cell line (CAL-27). CCK-8 assay suggested that miR-149-5p increased drug sensitivity in CAL-27 and CAL-27/CDDP cells. miR-149-5p attenuated proliferation, migration and invasion, and promoted apoptosis of CAL-27 and CAL-27/CDDP cells. In addition, TGFβ2 was up-regulated in OSCC cells at both mRNA and protein levels. Moreover, miR-149-5p promoted cisplatin chemosensitivity and regulated cell proliferation, apoptosis, migration and invasion by targeting TGFβ2 in CAL-27 and CAL-27/CDDP cells. CONCLUSION:miR-149-5p regulates cisplatin chemosensitivity, cell growth, apoptosis and metastasis by targeting TGFβ2. miR-149-5p/TGFβ2 axis has potential for therapy of OSCC. IJCEP