Ling-Fei Jia1, Yi-Ping Huang2, Yun-Fei Zheng3, Ming-Yue Lyu3, Su-Bi Wei4, Zhen Meng3, Ye-Hua Gan5. 1. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China; Laboratory of Molecular Biology, Peking University School and Hospital of Stomatology, Beijing 100081, China. 2. Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing 100081, China. 3. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China. 4. Medical Systems Biology Research Center, Tsinghua University, Beijing 100084, China. 5. Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing 100081, China; Laboratory of Molecular Biology, Peking University School and Hospital of Stomatology, Beijing 100081, China. Electronic address: kqyehuagan@bjmu.edu.cn.
Abstract
OBJECTIVES: miR-29b has been implicated in various cancers. However, the role of miR-29b in tongue squamous cell carcinoma (TSCC) remains unclear. This study aimed to investigate the role of miR-29b in TSCC progression. MATERIALS AND METHODS: The expression of miR-29b was analyzed in TSCC tissues and cells. Functional studies were performed in TSCC cells. Real time-PCR, Western blot, cell proliferation, transwell, and dual luciferase reporter assays were performed according to standard procedures. RESULTS: miR-29b was significantly decreased in TSCC specimens and cell lines compared with corresponding normal counterparts. Overexpression of miR-29b significantly inhibited the proliferation, migration, invasion, and cell-cycle progression of TSCC cells, and promoted apoptosis. Moreover, miR-29b targeted the 3' untranslated region of the Sp1 transcript and resulted in the deregulation of Sp1. The inhibition of Sp1 by miR-29b subsequently resulted in the upregulation of PTEN, leading to a decline of phosphorylated AKT. Knockdown of Sp1 in TSCC cell lines mimicked the effects of miR-29b overexpression. In addition, the expression of miR-29b was inversely correlated with Sp1 and positively correlated with the PTEN in TSCC specimens. CONCLUSION: miR-29b functions as a tumor suppressor in TSCC, and the miR-29b/Sp1/PTEN/AKT axis might represent a potential therapeutic target for TSCC intervention.
OBJECTIVES:miR-29b has been implicated in various cancers. However, the role of miR-29b in tongue squamous cell carcinoma (TSCC) remains unclear. This study aimed to investigate the role of miR-29b in TSCC progression. MATERIALS AND METHODS: The expression of miR-29b was analyzed in TSCC tissues and cells. Functional studies were performed in TSCC cells. Real time-PCR, Western blot, cell proliferation, transwell, and dual luciferase reporter assays were performed according to standard procedures. RESULTS:miR-29b was significantly decreased in TSCC specimens and cell lines compared with corresponding normal counterparts. Overexpression of miR-29b significantly inhibited the proliferation, migration, invasion, and cell-cycle progression of TSCC cells, and promoted apoptosis. Moreover, miR-29b targeted the 3' untranslated region of the Sp1 transcript and resulted in the deregulation of Sp1. The inhibition of Sp1 by miR-29b subsequently resulted in the upregulation of PTEN, leading to a decline of phosphorylated AKT. Knockdown of Sp1 in TSCC cell lines mimicked the effects of miR-29b overexpression. In addition, the expression of miR-29b was inversely correlated with Sp1 and positively correlated with the PTEN in TSCC specimens. CONCLUSION:miR-29b functions as a tumor suppressor in TSCC, and the miR-29b/Sp1/PTEN/AKT axis might represent a potential therapeutic target for TSCC intervention.
Authors: Anwar M Masoud; Syed W Bihaqi; Bothaina Alansi; Miriam Dash; Gehad M Subaiea; William E Renehan; Nasser H Zawia Journal: J Alzheimers Dis Date: 2018 Impact factor: 4.472