Department of Nutrition and Food Hygiene, School of Public Health, Anhui Medical University, Hefei, China.
Department of Gastroenterology, Lujiang County People's Hospital, Hefei, Anhui, China.
J Cancer Res Clin Oncol. 2022 Jan;148(1):121-135. doi: 10.1007/s00432-021-03820-2. Epub 2021 Oct 10.
Long noncoding RNAs (LncRNAs) play a pivotal role in gastric tumorigenesis, while exosomes facilitate the LncRNAs transferring to recipient cells. However, the roles of exosomal LncRNAs in gastric premalignant lesions (GPL) remain unclear.
We analyzed the expression of LncHOXA10 and its role in GPL progression. The protective effect of all-trans retinoic acid (ATRA) on GPL was explored in vitro and in vivo.
Here, we found that LncHOXA10 expression was obviously increased in serum exosomes and gastric tissues from individuals with GPL, and exosomal LncHOXA10 from patients with GPL markedly promoted the malignant progression of human gastric epithelial cell line GES-1. Furthermore, RNA-pulldown assay revealed that LncHOXA10 mainly interacted with pyruvate carboxylase (PC), an essential enzyme in various cellular metabolic pathways. In gastric tissues from patients with GPL and gastric cancer (GC), PC was also upregulated and positively correlated with LncHOXA10 expression, which predicted a poor prognosis as well. Moreover, PC silencing attenuated the malignant effects of exosomal LncHOXA10 on GES-1 cells. ATRA also ameliorated the deterioration of GPL and prevented the malignant progression of GPL by reducing exosomal LncHOXA10 and PC expression.
Collectively, the LncHOXA10-PC axis participated in the early stage of GC tumorigenesis, and ATRA might be useful to prevent GPL from developing into GC because it targets this axis.
长链非编码 RNA（lncRNAs）在胃肿瘤发生中发挥着关键作用，而外泌体则促进 lncRNAs 转移到受体细胞。然而，外泌体 lncRNAs 在胃前病变（GPL）中的作用尚不清楚。
我们分析了 LncHOXA10 的表达及其在 GPL 进展中的作用。体外和体内探讨了全反式视黄酸（ATRA）对 GPL 的保护作用。
在这里，我们发现 GPL 患者血清外泌体和胃组织中 LncHOXA10 的表达明显增加，来自 GPL 患者的外泌体 LncHOXA10 明显促进了人胃上皮细胞系 GES-1 的恶性进展。此外，RNA 下拉实验表明，LncHOXA10 主要与丙酮酸羧化酶（PC）相互作用，PC 是各种细胞代谢途径中的一种重要酶。在 GPL 和胃癌（GC）患者的胃组织中，PC 也上调，并与 LncHOXA10 的表达呈正相关，这也预示着预后不良。此外，沉默 PC 可减弱外泌体 LncHOXA10 对 GES-1 细胞的恶性作用。ATRA 还通过降低外泌体 LncHOXA10 和 PC 的表达来改善 GPL 的恶化，并防止 GPL 向 GC 恶性进展。
总之，LncHOXA10-PC 轴参与了 GC 肿瘤发生的早期阶段，ATRA 可能通过靶向该轴来预防 GPL 发展为 GC。
