Abstract

Growing evidence has indicated that the long noncoding RNA (lncRNA) CYTOR is involved in the initiation and progression of malignancies, including gastric cancer. Nevertheless, the mechanisms of CYTOR in gastric cancer development are not fully understood. In the present study, we aimed to clarify the association of CYTOR, miR-103, and RAB10 in gastric cancer progression. We found that CYTOR expression was increased in metastatic gastric cancer biopsies compared with that in primary samples. CYTOR expression was significantly positively correlated with the invasiveness, lymph node metastasis, and advanced stages of gastric cancer. In addition, downregulation of CYTOR expression hampered cell proliferation and migration but induced cell apoptosis. Furthermore, CYTOR sponged miR-103 and diminished miR-103 expression, thus rescuing oncogene RAB10 expression. Knockdown of CYTOR suppressed tumor growth in human BGC823 mouse models. These findings suggest that the CYTOR/miR-103/RAB10 axis is a novel signaling pathway that facilitates gastric cancer progression. CYTOR-targeted interventions provide a rationale to improve therapies targeting gastric cancer progression.

中文翻译：

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长链非编码 RNA CYTOR 通过靶向 miR-103/RAB10 触发胃癌进展

摘要

越来越多的证据表明，长链非编码 RNA (lncRNA) CYTOR 参与了包括胃癌在内的恶性肿瘤的发生和进展。然而，CYTOR 在胃癌发展中的机制尚不完全清楚。在本研究中，我们旨在阐明 CYTOR、miR-103 和 RAB10 在胃癌进展中的关联。我们发现与原始样本相比，转移性胃癌活检组织中的 CYTOR 表达增加。CYTOR的表达与胃癌的侵袭性、淋巴结转移和晚期分期显着正相关。此外，CYTOR 表达的下调会阻碍细胞增殖和迁移，但会诱导细胞凋亡。此外，CYTOR 吸收了 miR-103 并降低了 miR-103 的表达，从而挽救癌基因 RAB10 的表达。击倒CYTOR在人 BGC823 小鼠模型中抑制肿瘤生长。这些发现表明，CYTOR/miR-103/RAB10 轴是一种促进胃癌进展的新型信号通路。CYTOR 靶向干预为改善针对胃癌进展的治疗提供了依据。