Elevated pulmonary tuberculosis biomarker miR-423-5p plays critical role in the occurrence of active TB by inhibiting autophagosome-lysosome fusion
ABSTRACTRapid diagnosis of pulmonary tuberculosis is an effective measure to prevent the spread of tuberculosis. However, the grim fact is that the new, rapid, and safe methods for clinical diagnosis are lacking. Moreover, although auto-lysosome is critical in clearing Mycobacterium tuberculosis, th...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2019-01-01
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| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2019.1590129 |
| _version_ | 1797385795535896576 |
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| author | Huihui Tu Su Yang Tingting Jiang Liliang Wei Liying Shi Changming Liu Chong Wang Huai Huang Yuting Hu Zhongliang Chen Jing Chen Zhongjie Li Jicheng Li |
| author_facet | Huihui Tu Su Yang Tingting Jiang Liliang Wei Liying Shi Changming Liu Chong Wang Huai Huang Yuting Hu Zhongliang Chen Jing Chen Zhongjie Li Jicheng Li |
| author_sort | Huihui Tu |
| collection | DOAJ |
| description | ABSTRACTRapid diagnosis of pulmonary tuberculosis is an effective measure to prevent the spread of tuberculosis. However, the grim fact is that the new, rapid, and safe methods for clinical diagnosis are lacking. Moreover, although auto-lysosome is critical in clearing Mycobacterium tuberculosis, the pathological significance of microRNAs, as biomarkers of tuberculosis, in autophagosome maturation is unclear. Here, these microRNAs were investigated by Solexa sequencing and qPCR validation, and a potential diagnostic model was established by logistic regression. Besides that, the mechanism of one of the microRNAs involved in the occurrence of tuberculosis was studied. The results showed that the expression of miR-423-5p, miR-17-5p, and miR-20b-5p were significantly increased in the serum of patients with tuberculosis. The combination of these three microRNAs established a model to diagnose tuberculosis with an accuracy of 78.18%, and an area under the curve value of 0.908. Bioinformatics analysis unveiled miR-423-5p as the most likely candidate in regulating autophagosome maturation. The up-regulation of miR-423-5p could inhibit autophagosome maturation through suppressing autophagosome–lysosome fusion in macrophages. Further investigations showed that VPS33A was the direct target of miR-423-5p, and the two CUGCCCCUC domains in VPS33A 3’-UTR were the direct regulatory sites for miR-423-5p. In addition, an inverse correlation between VPS33A and miR-423-5p was found in peripheral blood mononuclear cells of patients with tuberculosis. Since the inhibition of autolysosome formation plays a critical role in tuberculosis occurrence, our findings suggests that miR-423-5p could suppress autophagosome–lysosome fusion by post-transcriptional regulation of VPS33A, which might be important for the occurrence of active tuberculosis. |
| first_indexed | 2024-03-08T21:59:25Z |
| format | Article |
| id | doaj.art-d327e24d59204df9b5f81ffb909edd38 |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2024-03-08T21:59:25Z |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-d327e24d59204df9b5f81ffb909edd382023-12-19T16:09:57ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512019-01-018144846010.1080/22221751.2019.1590129Elevated pulmonary tuberculosis biomarker miR-423-5p plays critical role in the occurrence of active TB by inhibiting autophagosome-lysosome fusionHuihui Tu0Su Yang1Tingting Jiang2Liliang Wei3Liying Shi4Changming Liu5Chong Wang6Huai Huang7Yuting Hu8Zhongliang Chen9Jing Chen10Zhongjie Li11Jicheng Li12Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaInstitute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaInstitute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaDepartment of Pneumology, Shaoxing Municipal Hospital, Shaoxing, People’s Republic of ChinaDepartment of Clinical Laboratory, Zhejiang Hospital, Hangzhou, People’s Republic of ChinaInstitute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaInstitute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaSchool of Medicine, South China University of Technology, Guangzhou, People’s Republic of ChinaSchool of Medicine, South China University of Technology, Guangzhou, People’s Republic of ChinaInstitute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaInstitute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaInstitute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaInstitute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaABSTRACTRapid diagnosis of pulmonary tuberculosis is an effective measure to prevent the spread of tuberculosis. However, the grim fact is that the new, rapid, and safe methods for clinical diagnosis are lacking. Moreover, although auto-lysosome is critical in clearing Mycobacterium tuberculosis, the pathological significance of microRNAs, as biomarkers of tuberculosis, in autophagosome maturation is unclear. Here, these microRNAs were investigated by Solexa sequencing and qPCR validation, and a potential diagnostic model was established by logistic regression. Besides that, the mechanism of one of the microRNAs involved in the occurrence of tuberculosis was studied. The results showed that the expression of miR-423-5p, miR-17-5p, and miR-20b-5p were significantly increased in the serum of patients with tuberculosis. The combination of these three microRNAs established a model to diagnose tuberculosis with an accuracy of 78.18%, and an area under the curve value of 0.908. Bioinformatics analysis unveiled miR-423-5p as the most likely candidate in regulating autophagosome maturation. The up-regulation of miR-423-5p could inhibit autophagosome maturation through suppressing autophagosome–lysosome fusion in macrophages. Further investigations showed that VPS33A was the direct target of miR-423-5p, and the two CUGCCCCUC domains in VPS33A 3’-UTR were the direct regulatory sites for miR-423-5p. In addition, an inverse correlation between VPS33A and miR-423-5p was found in peripheral blood mononuclear cells of patients with tuberculosis. Since the inhibition of autolysosome formation plays a critical role in tuberculosis occurrence, our findings suggests that miR-423-5p could suppress autophagosome–lysosome fusion by post-transcriptional regulation of VPS33A, which might be important for the occurrence of active tuberculosis.https://www.tandfonline.com/doi/10.1080/22221751.2019.1590129TuberculosismiR-423-5pdiagnostic biomarkerautophagosome-lysosome fusion; VPS33A |
| spellingShingle | Huihui Tu Su Yang Tingting Jiang Liliang Wei Liying Shi Changming Liu Chong Wang Huai Huang Yuting Hu Zhongliang Chen Jing Chen Zhongjie Li Jicheng Li Elevated pulmonary tuberculosis biomarker miR-423-5p plays critical role in the occurrence of active TB by inhibiting autophagosome-lysosome fusion Emerging Microbes and Infections Tuberculosis miR-423-5p diagnostic biomarker autophagosome-lysosome fusion; VPS33A |
| title | Elevated pulmonary tuberculosis biomarker miR-423-5p plays critical role in the occurrence of active TB by inhibiting autophagosome-lysosome fusion |
| title_full | Elevated pulmonary tuberculosis biomarker miR-423-5p plays critical role in the occurrence of active TB by inhibiting autophagosome-lysosome fusion |
| title_fullStr | Elevated pulmonary tuberculosis biomarker miR-423-5p plays critical role in the occurrence of active TB by inhibiting autophagosome-lysosome fusion |
| title_full_unstemmed | Elevated pulmonary tuberculosis biomarker miR-423-5p plays critical role in the occurrence of active TB by inhibiting autophagosome-lysosome fusion |
| title_short | Elevated pulmonary tuberculosis biomarker miR-423-5p plays critical role in the occurrence of active TB by inhibiting autophagosome-lysosome fusion |
| title_sort | elevated pulmonary tuberculosis biomarker mir 423 5p plays critical role in the occurrence of active tb by inhibiting autophagosome lysosome fusion |
| topic | Tuberculosis miR-423-5p diagnostic biomarker autophagosome-lysosome fusion; VPS33A |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2019.1590129 |
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