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Santerre M , Chatila W , Wang Y , Mukerjee R , Sawaya BE
HIV-1 Nef promotes cell proliferation and microRNA dysregulation in lung cells
Cell Cycle. 2019 Jan;18(2) :130-142
PMID: 30563405   
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Non-small cell lung cancer (NSCLC) represents about 85% of all lung cancer cases. Lung cancer is the most frequent non-AIDS-defining malignancies in HIV-infected patients. The mechanism of the increased risk for lung cancer in HIV-1 patients is poorly understood. HIV-1 Nef protein has been suggested to be one of the key players in HIV-related lung disease. In here, we showed the involvement of Nef protein in cell modifications such as fibroblasts (IMR-90) and normal (BEAS-2B) or cancerous (A549) epithelial cells. We demonstrated that Nef protein reprograms initial stages of lung cancer (e.g. changes in the metabolism, improved cell survival and invasion, increase the angiogenesis factor VEGF). Additionally, we showed that Nef is provoking a global decrease of mature miRNA and a decrease of DICER1 and AGO expression in lung cells. MiRNAs play a crucial role in cell signaling and homeostasis, functioning as oncogenes or tumor suppressors, and their dysregulation can contribute to the tumorigenic process. These results showed that HIV-1 Nef protein is directly involved in preventing cell death and contributes to tumor progression.
1551-4005 Santerre, Maryline Chatila, Wissam Wang, Ying Mukerjee, Ruma Sawaya, Bassel E R01 AG054411/AG/NIA NIH HHS/United States R01 MH093331/MH/NIMH NIH HHS/United States R01 NS076402/NS/NINDS NIH HHS/United States R01 NS059327/NS/NINDS NIH HHS/United States Journal Article Research Support, N.I.H., Extramural United States Cell Cycle. 2019 Jan;18(2):130-142. doi: 10.1080/15384101.2018.1557487. Epub 2019 Jan 6.