title: MicroRNA-520a attenuates proliferation of Raji cells through inhibition of AKT1/NF-κB and PERK/eIF2α signaling pathway.
abstract: Burkitt's lymphoma (BL) is a fast growing cancer of the human lymphatic system, and an extremely invasive B-cell non-Hodgkin's lymphoma. We explored the mechanism of apoptosis in Raji cells associated with the post-transcriptional regulation factors. To confirm that the predicted microRNA-520a (miR-520a) is matched with AKT1, 3' untranslated region (UTR) luciferase activity of AKT1 was used in the assessment. In the presence of the mimics or inhibitors of miR-520a, cell function of Raji, such as proliferation, growth and apoptosis were analyzed. The expression of endoplasmic reticulum (ER) stress‑related proteins were examined. Luciferase reporter analysis showed that miR‑520a leads to decreased activity of luciferase gene fused with AKT1 3'UTR. Therefore, AKT1 is a direct target of miR‑520a. Our data indicated that the mimics of miR‑520a inhibited growth, proliferation of Raji cells and promoted its apoptosis, which was related to downregulation of AKT1, NF‑κB and ER stress response mediated by PERK/eIF2α pathway. On the contrary, the inhibitors of miR‑520a promoted growth, proliferation of Raji cells and inhibited its apoptosis, which was related to AKT1/NF‑κB and PERK/eIF2α pathway. We identified miR‑520a, which specifically binds to AKT1 mRNA 3'UTR. miR‑520a is a crucial mediator for proliferation and ER stress in Raji cells through regulating the AKT1/NF‑κB or PERK/eIF2α signaling pathway. Our findings suggest that targeting miR‑520a is a promising therapeutic strategy in BL.
authors.affiliation: Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, The Second People's Hospital of Guangdong Province, Southern Medical University, Guangzhou, Guangdong 510317, P.R. China.
authors.forename: Pei
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, The Second People's Hospital of Guangdong Province, Southern Medical University, Guangzhou, Guangdong 510317, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Laboratory Medicine, The Second People's Hospital of Guangdong Province, Southern Medical University, Guangzhou, Guangdong 510317, P.R. China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, The Second People's Hospital of Guangdong Province, Southern Medical University, Guangzhou, Guangdong 510317, P.R. China.
authors.forename: Jinqian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wang
mesh_terms: D015153:Blotting, Western; D002051:Burkitt Lymphoma / Q000235:genetics / Q000473:pathology*; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D059865:Endoplasmic Reticulum Stress / Q000235:genetics*; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: D015852:Eukaryotic Initiation Factor-2; C575048:MIRN520 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C494918:AKT1 protein, human; C460640:EIF2AK3 protein, human; D051057:Proto-Oncogene Proteins c-akt; D019892:eIF-2 Kinase