LncRNAs are recently increasingly emerging as molecules that take its part in human carcinogenesis. A large body of literature has identified the functional roles of lncRNAs in the pathophysiology of CRC. The current study was intended to provide new ideas and perspectives for the functional role of lncRNA RAD51‐AS1 in regulating CRC progression. Herein, a survey of RAD51‐AS1 expression profile in The Cancer Genome Atlas (TCGA)‐colon adenocarcinoma (COAD) dataset revealed that RAD51‐AS1 was downregulated in COAD specimens. Consistently, RAD51‐AS1 expression was observed to be lower in CRC cell lines compared with normal cell line (NCM460). In the meanwhile, both the levels of miR‐29b‐3p and miR‐29c‐3p were prominently elevated in CRC cells. Functionally, administration of RAD51‐AS1 refrained growth, invasion and migration of CRC cells. Additionally, accumulation of RAD51‐AS1 hampered glucose consumption and lactate production, as well as the restraint of hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) levels. More important, RAD51‐AS1 functioned as a competing endogenous RNA (ceRNA) for sponging miR‐29b‐3p and miR‐29c‐3p, leading to enhancement of their common target N‐myc downstream‐regulated gene 2 (NDRG2). Mechanistically, the delivery of miR‐29b/c‐3p mimics or ablation of NDRG2 effectively blunted the salutary effects of RAD51‐AS1 on CRC cell behaviors. Moreover, augmentation of RAD51‐AS1 inhibited the tumorigenesis of CRC cells in vivo. Collectively, these findings provide comprehensive evidence that RAD51‐AS1 repressed cell proliferation, migration, invasion and glycolysis process, ultimately contributing to the progression of CRC by repressing the miR‐29b/c‐3p/NDRG2 signaling axis, insinuating the putative potential of RAD51‐AS1/miR‐29b/c‐3p/NDRG2 interaction network in unraveling CRC pathology and hopefully contributed to the treatment of CRC patients.

中文翻译：

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LncRNA RAD51-AS1/miR-29b/c-3p/NDRG2串扰抑制结直肠癌的增殖、侵袭和糖酵解

LncRNA 最近越来越多地作为参与人类致癌作用的分子出现。大量文献已经确定了 lncRNA 在 CRC 病理生理学中的功能作用。本研究旨在为 lncRNA RAD51-AS1 在调节 CRC 进展中的功能作用提供新的思路和观点。在此，对癌症基因组图谱 (TCGA)-结肠腺癌 (COAD) 数据集中 RAD51-AS1 表达谱的调查显示，RAD51-AS1 在 COAD 标本中下调。与正常细胞系 (NCM460) 相比，CRC 细胞系中的 RAD51-AS1 表达始终较低。同时，CRC细胞中miR-29b-3p和miR-29c-3p的水平均显着升高。在功能上，RAD51-AS1 的给药抑制了 CRC 细胞的生长、侵袭和迁移。此外，RAD51-AS1 的积累阻碍了葡萄糖的消耗和乳酸的产生，并抑制了己糖激酶 2 (HK2) 和葡萄糖转运蛋白 1 (GLUT1) 的水平。更重要的是，RAD51-AS1 作为一种竞争性内源性 RNA (ceRNA) 作用于 miR-29b-3p 和 miR-29c-3p，从而增强了它们共同的靶标 N-myc 下游调节基因 2 (NDRG2)。从机制上讲，miR-29b/c-3p 模拟物的传递或 NDRG2 的消融有效地减弱了 RAD51-AS1 对 CRC 细胞行为的有益作用。此外，RAD51-AS1 的增强抑制了体内 CRC 细胞的肿瘤发生。总的来说，这些发现提供了全面的证据表明 RAD51-AS1 抑制细胞增殖、迁移、侵袭和糖酵解过程，