BACKGROUND: Glioma is the most common malignant tumor in the adult human brain and has one of the lowest patient survival rates. MicroRNAs (miRNAs) play important roles in the development of cancers, including glioma, and potentially have valuable therapeutic applications in glioma; however, their specific functions and mechanisms of action have yet to be fully defined. Here, we report that miR-129-5p directly targets DNA (cytosine-5)-methyltransferase 3A (DNMT3A) and functions as a tumor-suppressor in glioma. METHOD: We analyzed the expression profiles of miR-129-5p and DNMT3A in glioma-related databases. Quantitative reverse transcription-PCR was applied to detect the level of miR-129-5p in glioma specimens and cell lines. Western blotting was applied to detect the level of DNMT3A. We examined the effect of miR-129-5p on the cell cycle and proliferation of glioma cells using CCK-8 and EDU assays and flow cytometry. TargetScan software predicted DNMT3A to be a target of miR-129-5p, which we confirmed by means of luciferase reporter assays and rescue experiments. RESULT: miR-129-5p was expressed at low levels in glioma and negatively correlated with glioma grade. Over-expression of miR-129-5p in U87and LN229 cells inhibited proliferation and blocked the cell cycle in G1 Phase. DNMT3A is a direct target of miR-129-5p, and miR-129-5p affects glioma cell proliferation by targeting DNMT3A. CONCLUSION: Taken together, our results demonstrate that miR-129-5p plays a significant role in glioma suppression through inhibition of DNMT3A, which may provide a novel therapeutic strategy for treatment of glioma and other DNMT3A-driven cancers.
BACKGROUND:Glioma is the most common malignant tumor in the adult human brain and has one of the lowest patient survival rates. MicroRNAs (miRNAs) play important roles in the development of cancers, including glioma, and potentially have valuable therapeutic applications in glioma; however, their specific functions and mechanisms of action have yet to be fully defined. Here, we report that miR-129-5p directly targets DNA (cytosine-5)-methyltransferase 3A (DNMT3A) and functions as a tumor-suppressor in glioma. METHOD: We analyzed the expression profiles of miR-129-5p and DNMT3A in glioma-related databases. Quantitative reverse transcription-PCR was applied to detect the level of miR-129-5p in glioma specimens and cell lines. Western blotting was applied to detect the level of DNMT3A. We examined the effect of miR-129-5p on the cell cycle and proliferation of glioma cells using CCK-8 and EDU assays and flow cytometry. TargetScan software predicted DNMT3A to be a target of miR-129-5p, which we confirmed by means of luciferase reporter assays and rescue experiments. RESULT: miR-129-5p was expressed at low levels in glioma and negatively correlated with glioma grade. Over-expression of miR-129-5p in U87and LN229 cells inhibited proliferation and blocked the cell cycle in G1 Phase. DNMT3A is a direct target of miR-129-5p, and miR-129-5p affects glioma cell proliferation by targeting DNMT3A. CONCLUSION: Taken together, our results demonstrate that miR-129-5p plays a significant role in glioma suppression through inhibition of DNMT3A, which may provide a novel therapeutic strategy for treatment of glioma and other DNMT3A-driven cancers.
Authors: David N Louis; Arie Perry; Guido Reifenberger; Andreas von Deimling; Dominique Figarella-Branger; Webster K Cavenee; Hiroko Ohgaki; Otmar D Wiestler; Paul Kleihues; David W Ellison Journal: Acta Neuropathol Date: 2016-05-09 Impact factor: 17.088
Authors: Timothy J Ley; Li Ding; Matthew J Walter; Michael D McLellan; Tamara Lamprecht; David E Larson; Cyriac Kandoth; Jacqueline E Payton; Jack Baty; John Welch; Christopher C Harris; Cheryl F Lichti; R Reid Townsend; Robert S Fulton; David J Dooling; Daniel C Koboldt; Heather Schmidt; Qunyuan Zhang; John R Osborne; Ling Lin; Michelle O'Laughlin; Joshua F McMichael; Kim D Delehaunty; Sean D McGrath; Lucinda A Fulton; Vincent J Magrini; Tammi L Vickery; Jasreet Hundal; Lisa L Cook; Joshua J Conyers; Gary W Swift; Jerry P Reed; Patricia A Alldredge; Todd Wylie; Jason Walker; Joelle Kalicki; Mark A Watson; Sharon Heath; William D Shannon; Nobish Varghese; Rakesh Nagarajan; Peter Westervelt; Michael H Tomasson; Daniel C Link; Timothy A Graubert; John F DiPersio; Elaine R Mardis; Richard K Wilson Journal: N Engl J Med Date: 2010-11-10 Impact factor: 91.245
Authors: Lars Dyrskjøt; Marie S Ostenfeld; Jesper B Bramsen; Asli N Silahtaroglu; Philippe Lamy; Ramshanker Ramanathan; Niels Fristrup; Jens L Jensen; Claus L Andersen; Karsten Zieger; Sakari Kauppinen; Benedicte P Ulhøi; Jørgen Kjems; Michael Borre; Torben F Orntoft Journal: Cancer Res Date: 2009-06-01 Impact factor: 12.701