Contribution of microRNA-30d to the prevention of the thyroid cancer occurrence and progression: mechanism and implications

Springer Science and Business Media LLC - Tập 28 - Trang 576-593 - 2023
Yanqi Li1, Yuan He2, Yuan Chen3, Zhaocai He2, Fan Yang2, Chungen Xing1
1Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, P.R. China
2Department of General Surgery, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, P.R. China
3Department of General Surgery, Tumor Hospital Affiliated to Nantong University, Nantong, P.R. China

Tóm tắt

Thyroid cancer is a major endocrine tumor and represents an emerging health problem worldwide. MicroRNAs (miRNAs) have been addressed to participate in the pathogenesis and progression of thyroid cancer. However, it remains largely unknown what functions miR-30d may exert on thyroid cancer. This study, herein, aimed to identify the functional significance and machinery of miR-30d in the progression of thyroid cancer. MiR-30b presented aberrant low expression and ubiquitin-specific protease 22 (USP22) exhibited aberrant high expression in thyroid cancer tissues and cells. The current study proposed the possible machinery that miR-30d could target and negatively regulate USP22. Additionally, USP22 could enhance the stability of SIRT1 by inducing deubiquitination which consequently contributed to FOXO3a deacetylation-induced PUMA repression. Responding to the gain- or loss-of-function of miR-30d and/or USP22, behaviors of thyroid cancer cells were altered. Accordingly, miR-30d inhibited proliferation and promoted apoptosis of thyroid cancer cells by suppressing USP22 through SIRT1/FOXO3a/PUMA axis. The effects of miR-30d and USP22-mediated SIRT1/FOXO3a/PUMA axis on thyroid tumorigenesis were finally validated in murine models. We ultimately confirmed the anti-proliferative and pro-apoptotic effect of miR-30d via suppressing USP22 through in vivo findings. Conclusively, our findings highlight that the occurrence and progression of thyroid cancer can be suppressed by miR-30d-mediated inhibition of USP22 via the SIRT1/FOXO3a/PUMA axis, which provides a attractive therapeutic target for thyroid cancer treatment.

Tài liệu tham khảo

Jin J (2017) JAMA patient page. Screen Thyroid Cancer JAMA 317(18):1920

Visone R, Pallante P, Vecchione A, Cirombella R, Ferracin M, Ferraro A, Volinia S, Coluzzi S, Leone V, Borbone E, Liu CG, Petrocca F, Troncone G, Calin GA, Scarpa A, Colato C, Tallini G, Santoro M, Croce CM, Fusco A (2007) Specific microRNAs are downregulated in human thyroid anaplastic carcinomas. Oncogene 26(54):7590–7595