Exosomal circ_0026611 contributes to lymphangiogenesis by reducing PROX1 acetylation and ubiquitination in human lymphatic endothelial cells (HLECs)

Cellular & Molecular Biology Letters

Research

Tian Xia¹  Lei Xu¹  Quan Zhang¹  Xiangbo Jia¹  Wenjian Yao¹  Li Wei¹  Li Zhu² 

[1] Department of Thoracic Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, No.7, Weiwu Road, Jinshui District, 450003, Zhengzhou, Henan, China;Department of Thoracic Surgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, 450003, Zhengzhou, Henan, China;

关键词: Esophageal squamous cell carcinoma;    Exosomes;    circ_0026611;    PROX1;    Lymphangiogenesis;   

DOI  :  10.1186/s11658-022-00410-z

 received in 2022-05-08, accepted in 2022-11-24,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundEsophageal squamous carcinoma (ESCC) is a common malignancy that originates in the digestive tract. Lymph node metastasis (LNM) is a complicated process, and tumor lymphangiogenesis has been reported to be associated with the spread of tumor cells to lymph nodes (LNs), including in ESCC. However, little is currently known about the mechanisms involved in lymphangiogenesis in ESCC tumors. According to previous literature, we know that hsa_circ_0026611 expresses at a high level in serum exosomes of patients with ESCC and shows a close association with LNM and poor prognosis. However, details on the functions of circ_0026611 in ESCC remain unclear. We aim to explore the effects of circ_0026611 in ESCC cell-derived exosomes on lymphangiogenesis and its potential molecular mechanism.MethodsWe firstly examined how circ_0026611 may express in ESCC cells and exosomes by quantitative reverse transcription real-time polymerase chain reaction (RT-qPCR). The potential effects circ_0026611 may exert on lymphangiogenesis in ESCC cell-derived exosomes were assessed afterward via mechanism experiments.Resultscirc_0026611 high expression pattern was confirmed in ESCC cells and exosomes. ESCC cell-derived exosomes promoted lymphangiogenesis by transferring circ_0026611. Besides, circ_0026611 interacted with N-α-acetyltransferase 10 (NAA10) to inhibit NAA10-mediated prospero homeobox 1 (PROX1) acetylation with subsequent ubiquitination and degradation. Furthermore, circ_0026611 was verified to promote lymphangiogenesis in a PROX1-mediated manner.ConclusionsExosomal circ_0026611 inhibited PROX1 acetylation and ubiquitination to promote lymphangiogenesis in ESCC.Graphical Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

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