title: Down-regulation of miR-20a-5p triggers cell apoptosis to facilitate mycobacterial clearance through targeting JNK2 in human macrophages.
abstract: Induction of cell apoptosis is one of the major host defense mechanisms through which macrophages control Mycobacterium tuberculosis (Mtb) infection. However, the mechanisms underlying macrophage apoptosis triggered by Mtb infection are still largely unknown. In this study, a microarray profiling survey revealed 14 miRNAs were down-regulated in CD14+ monocytes from active pulmonary tuberculosis patients, and only the reduction of miR-20a-5p could be reversed after successful anti-tuberculosis treatment. Validation of miR-20a-5p expression was confirmed using real time qPCR. Moreover, miR-20a-5p expression also decreased in differentiated THP-1 macrophages after mycobacterial infection in vitro. Functional assays through forced or inhibited expression of miR-20a-5p in THP-1 macrophages demonstrated that miR-20a-5p functioned as a negative regulator of mycobacterial-triggered apoptosis. Importantly, inhibition of miR-20a-5p expression resulted in more efficient mycobacterial clearance from infected THP-1 macrophages while miR-20a-5p overexpression promoted mycobacterial survival. Mechanistically, miR-20a-5p was demonstrated to regulate Bim expression in a JNK2-dependent manner, unlike Bcl2, and luciferase assay showed JNK2 was a novel direct target of miR-20a-5p. Together, our findings indicate that downregulation of miR-20a-5p triggers macrophage apoptosis as a novel mechanism for host defense against mycobacterial infection.
authors: a Guangdong Key Lab for Diagnosis & Treatment of Emerging Infectious Diseases, Shenzhen Key Lab of Infection & Immunity, Shenzhen Third People's Hospital, Guangdong Medical University , Shenzhen , China.|b Department of Infectious Diseases and Immunology , Sydney Medical School, The University of Sydney , NSW , Australia.
authors: Guoliang
authors: G
authors: Zhang
authors: c Department of Infectious Diseases , The Fifth Affiliated Hospital, Sun Yat-sen University , Zhuhai , China.
authors: Xi
authors: X
authors: Liu
authors: a Guangdong Key Lab for Diagnosis & Treatment of Emerging Infectious Diseases, Shenzhen Key Lab of Infection & Immunity, Shenzhen Third People's Hospital, Guangdong Medical University , Shenzhen , China.
authors: Wenfei
authors: W
authors: Wang
authors: a Guangdong Key Lab for Diagnosis & Treatment of Emerging Infectious Diseases, Shenzhen Key Lab of Infection & Immunity, Shenzhen Third People's Hospital, Guangdong Medical University , Shenzhen , China.
authors: Yi
authors: Y
authors: Cai
authors: a Guangdong Key Lab for Diagnosis & Treatment of Emerging Infectious Diseases, Shenzhen Key Lab of Infection & Immunity, Shenzhen Third People's Hospital, Guangdong Medical University , Shenzhen , China.
authors: Shaoyuan
authors: S
authors: Li
authors: a Guangdong Key Lab for Diagnosis & Treatment of Emerging Infectious Diseases, Shenzhen Key Lab of Infection & Immunity, Shenzhen Third People's Hospital, Guangdong Medical University , Shenzhen , China.
authors: Qi
authors: Q
authors: Chen
authors: a Guangdong Key Lab for Diagnosis & Treatment of Emerging Infectious Diseases, Shenzhen Key Lab of Infection & Immunity, Shenzhen Third People's Hospital, Guangdong Medical University , Shenzhen , China.
authors: Mingfeng
authors: M
authors: Liao
authors: a Guangdong Key Lab for Diagnosis & Treatment of Emerging Infectious Diseases, Shenzhen Key Lab of Infection & Immunity, Shenzhen Third People's Hospital, Guangdong Medical University , Shenzhen , China.
authors: Mingxia
authors: M
authors: Zhang
authors: d Department of Microbiology , Zhongshan School of Medicine, Sun Yat-sen University , Guangzhou , China.
authors: Gucheng
authors: G
authors: Zeng
authors: a Guangdong Key Lab for Diagnosis & Treatment of Emerging Infectious Diseases, Shenzhen Key Lab of Infection & Immunity, Shenzhen Third People's Hospital, Guangdong Medical University , Shenzhen , China.
authors: Boping
authors: B
authors: Zhou
authors: a Guangdong Key Lab for Diagnosis & Treatment of Emerging Infectious Diseases, Shenzhen Key Lab of Infection & Immunity, Shenzhen Third People's Hospital, Guangdong Medical University , Shenzhen , China.|b Department of Infectious Diseases and Immunology , Sydney Medical School, The University of Sydney , NSW , Australia.
authors: Carl G
authors: CG
authors: Feng
authors: a Guangdong Key Lab for Diagnosis & Treatment of Emerging Infectious Diseases, Shenzhen Key Lab of Infection & Immunity, Shenzhen Third People's Hospital, Guangdong Medical University , Shenzhen , China.|e Department of Pathogen , Shenzhen University School of Medicine , Shenzhen , China.
authors: Xinchun
authors: X
authors: Chen
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D000072224:Bcl-2-Like Protein 11 / Q000378:metabolism; D002460:Cell Line; D015536:Down-Regulation / Q000235:genetics*; D006801:Humans; D008264:Macrophages / Q000201:enzymology* / Q000382:microbiology* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D014397:Tuberculosis, Pulmonary / Q000201:enzymology / Q000235:genetics / Q000382:microbiology / Q000473:pathology
chemical_list: D000072224:Bcl-2-Like Protein 11; C534451:MIRN20a microRNA, human; D035683:MicroRNAs; D048056:Mitogen-Activated Protein Kinase 9
keywords: JNK2; apoptosis; macrophages; miR-20a-5p; mycobacterial