IRGM promotes melanoma cell survival through autophagy and is a promising prognostic biomarker for clinical application
| Autor: | Zilin Shi, Linlu Tian, Ruijie Liu, Hongwei Xu, Yue Yang, Xinlei Li, Lie Zhang, Xiao Dong, Bo Li, Rui Li, Hulun Li, Chunying Pei, Hongxue Meng |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research autophagy Regulator Chromosomal translocation GTPase HMGB1 lcsh:RC254-282 Metastasis 03 medical and health sciences 0302 clinical medicine medicine Pharmacology (medical) Melanoma prognostic biomaker biology Autophagy lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease IRGM 030104 developmental biology Oncology 030220 oncology & carcinogenesis biology.protein Cancer research Molecular Medicine Original Article |
| Zdroj: | Molecular Therapy Oncolytics Molecular Therapy: Oncolytics, Vol 20, Iss, Pp 187-198 (2021) |
| ISSN: | 2372-7705 |
| Popis: | Previously, we showed that mouse immunity-related guanosine triphosphatase (GTPase) family M protein 1 (Irgm1) promotes malignant melanoma progression by inducing cellular autophagy flux and metastasis. Human IRGM, a truncated protein functionally distinct from its mouse counterpart, has several splice isoforms. In this study, we analyzed the association of IRGM and human melanoma clinical prognosis and investigated the function of IRGM in human melanoma cells. Data from the training cohort (n = 144) showed that overexpression of IRGM is proportional to melanoma genesis and clinical stages in human tissue chips. A validation cohort (n = 78) further confirmed that IRGM is an independent risk factor promoting melanoma progression and is associated with poor survival of patients. Among IRGM isoforms, we found that IRGMb is responsible for such correlation. In addition, IRGM promoted melanoma cell survival through autophagy, both in vitro and in vivo. We further showed that the blockade of translocation of high-mobility group box 1 (HMGB1) from the nucleus to cytoplasm inhibits IRGM1-mediated cellular autophagy and reduces cell survival. IRGM functions as a positive regulator of melanoma progression through autophagy and may serve as a promising prognostic marker and therapeutic target. Graphical Abstract Human IRGM overexpression in melanoma is associated with more advanced clinical stages, stronger metastasis, and poor survival. IRGM coupled with HMGB-1 enhanced melanoma cell survival through increasing autophagy. Our observations support utility of IRGM as a prognostic marker and potential therapeutic target for melanoma. |
| Databáze: | OpenAIRE |
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