Wang Chen, Zhao Didi, Wang Kexin, Gao Lei, He Yue, Wu Hanhan, Ruan Liang, Chen Wenjun, Zhang Daoming, Xia Tao, Qian Shiqing, Liu Zhining, Yang Yi, Yang Wanshui, Hu Anla, Zhao Qihong
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 Province, China.
Nutr Cancer. 2021;73(10):2065-2077. doi: 10.1080/01635581.2020.1823006. Epub 2020 Sep 22.
Numerous long noncoding RNAs (LncRNAs) were having recently been shown to be involved in cancer development, including gastric cancer (GC). However, the precise mechanism and treatments to target these molecules have rarely been studied. Thus, we aimed to investigate the function of LncHOXA10 in gastric tumorigenesis and targeted therapy. First, we measured the differences in LncHOXA10 and retinoic acid receptor β (RAR-β) levels in gastric cancer tissues and cell lines compared with those in noncancerous tissues and cell lines. We observed that LncHOXA10 was significantly upregulated in gastric cancer tissues and cell lines, whereas RAR-β showed the opposite trend. Subsequently, loss and gain of LncHOXA10 cell lines were constructed to determine whether LncHOXA10 plays a role in gastric tumorigenesis. The results showed that LncHOXA10 promoted the proliferation, migration, and invasion of cells, whereas apoptosis was markedly inhibited. Subsequently, mechanistic investigations revealed that LncHOXA10 can repress RAR-β expression and that all-trans retinoic acid (ATRA) can rescue the expression of RAR-β. Finally, we showed that ATRA can reverse the pro-cancerous function of LncHOXA10. We showed that LncHOXA10 may be a prognostic and therapeutic factor of gastric cancer by negatively regulating RAR-β. Furthermore, ATRA can inhibit the role of LncHOXA10 in gastric tumorigenesis.
最近有研究表明，众多长链非编码RNA（LncRNAs）参与癌症发展，包括胃癌（GC）。然而，针对这些分子的精确机制和治疗方法鲜有研究。因此，我们旨在研究LncHOXA10在胃癌发生和靶向治疗中的作用。首先，我们检测了胃癌组织和细胞系中LncHOXA10和视黄酸受体β（RAR-β）水平与非癌组织和细胞系中的差异。我们观察到，LncHOXA10在胃癌组织和细胞系中显著上调，而RAR-β则呈现相反趋势。随后，构建了LncHOXA10细胞系的缺失和过表达模型，以确定LncHOXA10是否在胃癌发生中起作用。结果表明，LncHOXA10促进细胞增殖、迁移和侵袭，而细胞凋亡则明显受到抑制。随后的机制研究表明，LncHOXA10可抑制RAR-β表达，全反式维甲酸（ATRA）可挽救RAR-β的表达。最后，我们表明ATRA可逆转LncHOXA10的促癌功能。我们发现，LncHOXA10可能通过负向调节RAR-β成为胃癌的一个预后和治疗因子。此外，ATRA可抑制LncHOXA10在胃癌发生中的作用。
