Urolithin A promotes the degradation of TMSB10 to deformation F-actin in non-small-cell lung cancer

Miaomiao Li; Hao Cui; Huan Deng; Yanjuan Deng; Sheng Yin; Tianzhi Li; Tao Yuan

doi:10.1016/j.phymed.2024.156109

Urolithin A promotes the degradation of TMSB10 to deformation F-actin in non-small-cell lung cancer

Phytomedicine. 2024 Sep 29:135:156109. doi: 10.1016/j.phymed.2024.156109. Online ahead of print.

Authors

Miaomiao Li¹, Hao Cui², Huan Deng³, Yanjuan Deng⁴, Sheng Yin⁵, Tianzhi Li⁶, Tao Yuan⁷

Affiliations

¹ School of Health, Jiangxi Normal University, Jiangxi Province Key Laboratory of Natural and Biomimetic Drugs Research, Nanchang, 330022, China; College of Life Science, Jiangxi Normal University, Nanchang, 330022, China.
² College of Life Science, Jiangxi Normal University, Nanchang, 330022, China.
³ Rehabiliation Hospital, Jiangxi Medical College, Nanchang University, 330006, Nanchang, Jiangxi, China; Tumor Immunology Institute, Nanchang University, 330006, Nanchang, Jiangxi, China; The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Jiangxi Medical College, Nanchang University, 330031, Nanchang, Jiangxi, China.
⁴ Rehabiliation Hospital, Jiangxi Medical College, Nanchang University, 330006, Nanchang, Jiangxi, China; Tumor Immunology Institute, Nanchang University, 330006, Nanchang, Jiangxi, China.
⁵ School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, 510006, China.
⁶ School of Health, Jiangxi Normal University, Jiangxi Province Key Laboratory of Natural and Biomimetic Drugs Research, Nanchang, 330022, China. Electronic address: Tianzhi_li@jxnu.edu.cn.
⁷ School of Health, Jiangxi Normal University, Jiangxi Province Key Laboratory of Natural and Biomimetic Drugs Research, Nanchang, 330022, China; College of Life Science, Jiangxi Normal University, Nanchang, 330022, China. Electronic address: tyuan@jxnu.edu.cn.

PMID: 39368341
DOI: 10.1016/j.phymed.2024.156109

Abstract

Background: Lung cancer is one of the most frequently diagnosed cancers and non-small-cell lung cancer (NSCLC) poses major diagnoses. Urolithin A (UA) is a natural compound produced by the gut microbiota through the metabolism of polyphenol ellagitannins (ETs) and ellagic acid (EA), which has been found to inhibit epithelial-mesenchymal transition (EMT) in lung cancer cell lines. However, the mechanism of UA function in NSCLC remains elusive.

Propose: This study aimed to investigate the potential effectiveness of UA in NSCLC therapeutic and uncovering its underlying mechanisms.

Methods: Effects of UA treatment, TMSB10 gene knockdown or overexpression on NSCLC cell phenotype were evaluated by availability, transwell assays. The downstream factors and pathways of UA were investigated by proteomics. TMSB10 expression in NSCLC tissues was detected by bioinformatics analysis as well as immunohistochemistry. Confocal imaging, GST pull-down and western blotting investigated the mechanism of UA induced TMSB10 degradation.

Results: In the present study, we demonstrated that UA shows an inhibitory role in NSCLC cell proliferation, migration, and invasion. This inhibition is attributed to the accelerated degradation of TMSB10, a biomarker among various cancers, via the autophagy-lysosome pathway. Additionally, knocked down of TMSB10 showed a similar phenotype with UA treatment. The reduction of TMSB10 protein level following decreased ATP level inhibits the F-actin formation for cell migration, thereby disrupting the equilibrium between G-actin-TMSB10 and G-actin-ATP interactions in A549 cells.

Conclusion: Our results reveal that UA is potential for NSCLC therapeutics through reducing the protein level of TMSB10 to deformation the F-actin.

Keywords: ATP level; Degradation; G-actin; NSCLC; Natural compound.