BACKGROUND: Our previous findings showed that miR-33 expressed abnormally in clinical specimens of melanoma, but the exact molecular mechanism has not been elucidated. OBJECT: To determine miR-33's roles in melanoma and confirm whether HIF-1α is a direct target gene of miR-33a. METHODS: First miR-33a/b expression levels were detected in HM, WM35, WM451, A375 and SK-MEL-1. Then lentiviral vectors were constructed to intervene miR-33a expression in melanoma cells. Cell proliferation, invasion and metastasis were detected. A375 cells mice model was performed to test the tumorigenesis of melanoma in vivo. Finally the dual reporter gene assay was carried out to confirm whether HIF-1α is a direct target gene of miR-33a. RESULTS: MiR-33a/b exhibited a lower expression in WM35, WM451, A375 and SK-MEL-1 of the metastatic skin melanoma cell lines than that in HM. Then inhibition of miR-33a expression in WM35 and WM451 cell lines could promote cell proliferation, invasion and metastasis. Conversely, increased expression of miR-33a in A375 cells could inhibit cellproliferation, invasion and metastasis. In vivo tests also confirmed that overexpression of miR-33a in A375 cells significantly inhibited melanoma tumorigenesis. Finally, we confirmed that HIF-1α is a direct target gene of miR-33a. CONCLUSION: The newly identified miR-33a/HIF-1α axis might provide a new strategy for the treatment of melanoma.
BACKGROUND: Our previous findings showed that miR-33 expressed abnormally in clinical specimens of melanoma, but the exact molecular mechanism has not been elucidated. OBJECT: To determine miR-33's roles in melanoma and confirm whether HIF-1α is a direct target gene of miR-33a. METHODS: First miR-33a/b expression levels were detected in HM, WM35, WM451, A375 and SK-MEL-1. Then lentiviral vectors were constructed to intervene miR-33a expression in melanoma cells. Cell proliferation, invasion and metastasis were detected. A375 cells mice model was performed to test the tumorigenesis of melanoma in vivo. Finally the dual reporter gene assay was carried out to confirm whether HIF-1α is a direct target gene of miR-33a. RESULTS:MiR-33a/b exhibited a lower expression in WM35, WM451, A375 and SK-MEL-1 of the metastatic skin melanoma cell lines than that in HM. Then inhibition of miR-33a expression in WM35 and WM451 cell lines could promote cell proliferation, invasion and metastasis. Conversely, increased expression of miR-33a in A375 cells could inhibit cellproliferation, invasion and metastasis. In vivo tests also confirmed that overexpression of miR-33a in A375 cells significantly inhibited melanoma tumorigenesis. Finally, we confirmed that HIF-1α is a direct target gene of miR-33a. CONCLUSION: The newly identified miR-33a/HIF-1α axis might provide a new strategy for the treatment of melanoma.
Authors: M Thomas; K Lange-Grünweller; U Weirauch; D Gutsch; A Aigner; A Grünweller; R K Hartmann Journal: Oncogene Date: 2011-07-11 Impact factor: 9.867
Authors: Alexandra Giatromanolaki; Efthimios Sivridis; Constantinos Kouskoukis; Kevin C Gatter; Adrian L Harris; Michael I Koukourakis Journal: Melanoma Res Date: 2003-10 Impact factor: 3.599
Authors: Sara C Hanna; Bhavani Krishnan; Sean T Bailey; Stergios J Moschos; Pei-Fen Kuan; Takeshi Shimamura; Lukas D Osborne; Marni B Siegel; Lyn M Duncan; E Tim O'Brien; Richard Superfine; C Ryan Miller; M Celeste Simon; Kwok-Kin Wong; William Y Kim Journal: J Clin Invest Date: 2013-04-08 Impact factor: 14.808
Authors: Katey J Rayner; Christine C Esau; Farah N Hussain; Allison L McDaniel; Stephanie M Marshall; Janine M van Gils; Tathagat D Ray; Frederick J Sheedy; Leigh Goedeke; Xueqing Liu; Oleg G Khatsenko; Vivek Kaimal; Cynthia J Lees; Carlos Fernandez-Hernando; Edward A Fisher; Ryan E Temel; Kathryn J Moore Journal: Nature Date: 2011-10-19 Impact factor: 49.962