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, Zhengzhou, 450003, Henan, China.
Department of Thoracic Surgery, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, 450003, Henan, China.
Cell Mol Biol Lett. 2023 Feb 17;28(1):13. doi: 10.1186/s11658-022-00410-z.
Esophageal 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.
We 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.
circ_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.
Exosomal circ_0026611 inhibited PROX1 acetylation and ubiquitination to promote lymphangiogenesis in ESCC.
食管鳞状细胞癌（ESCC）是一种常见的起源于消化道的恶性肿瘤。淋巴结转移（LNM）是一个复杂的过程，据报道肿瘤淋巴管生成与肿瘤细胞向淋巴结（LNs）的扩散有关，包括 ESCC。然而，目前对于 ESCC 肿瘤中淋巴管生成的机制知之甚少。根据之前的文献，我们知道 hsa_circ_0026611 在 ESCC 患者血清外泌体中高表达，并与 LNM 和预后不良密切相关。然而，circ_0026611 在 ESCC 中的功能细节尚不清楚。我们旨在探讨 circ_0026611 在 ESCC 细胞衍生的外泌体中对淋巴管生成的影响及其潜在的分子机制。
我们首先通过定量逆转录实时聚合酶链反应（RT-qPCR）检查 circ_0026611 如何在外泌体中表达。此后，通过机制实验评估 circ_0026611 在外泌体中对 ESCC 细胞淋巴管生成的潜在影响。
circ_0026611 在 ESCC 细胞和外泌体中呈高表达模式。ESCC 细胞衍生的外泌体通过转移 circ_0026611 促进淋巴管生成。此外，circ_0026611 与 N-α-乙酰转移酶 10（NAA10）相互作用，抑制 NAA10 介导的同源盒蛋白 1（PROX1）乙酰化，随后发生泛素化和降解。此外，circ_0026611 被证实以 PROX1 介导的方式促进淋巴管生成。
外泌体 circ_0026611 通过抑制 PROX1 的乙酰化和泛素化促进 ESCC 中的淋巴管生成。
