Colorectal liver metastasis (CRCLM) is the leading cause of death in patients with colorectal cancer (CRC). MiR-30b-5p can function as an oncogene or tumor suppressor in cancers, but its role in CRCLM is still unknown. Here, we found that miR-30b-5p overexpression suppressed the invasion, migration, adhesion, and motility of HCT116 and LoVo cells. The expression of EMT (Zeb1, Snail, and vimentin) and adhesion-related proteins (p-paxillin and p-Src) was decreased. We validated Rap1b, a Ras family small GTPase that regulates cell adhesion and mobility, as the direct and functional target of miR-30b-5p. Rap1b overexpression rescued the aggressive characteristics of CRC cells that were inhibited by miR-30b-5p. Rap1b knockdown suppressed invasion and migration and decreased CRC cell-matrix adhesion and spreading, which was consistent with the results of miR-30b-5p overexpression. Further in vivo experiments demonstrated that miR-30b-5p overexpression inhibited CRCLM, but Rap1b rescue attenuated the inhibitory effect of miR-30b-5p. In addition, miR-30b-5p was downregulated in CRC specimens, and Rap1b showed a negative correlation with miR-30b-5p expression in primary CRC and LM tissues. These results indicate that miR-30b-5p functions as a metastasis suppressor by targeting Rap1b and may provide a new target for the treatment of CRCLM.

中文翻译：

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通过靶向Rap1b，MicroRNA-30b-5p在结肠直肠癌中起转移抑制作用。

大肠肝转移（CRCLM）是大肠癌（CRC）患者死亡的主要原因。MiR-30b-5p可以在癌症中起癌基因或抑癌作用，但其在CRCLM中的作用仍然未知。在这里，我们发现miR-30b-5p过表达抑制了HCT116和LoVo细胞的侵袭，迁移，粘附和运动。EMT（Zeb1，Snail和波形蛋白）和粘附相关蛋白（p-paxillin和p-Src）的表达降低。我们验证了Rap1b，它是一种Ras家族的小GTP酶，它调节细胞粘附和迁移，是miR-30b-5p的直接和功能靶标。Rap1b过表达挽救了被miR-30b-5p抑制的CRC细胞的侵袭性特征。Rap1b基因敲低抑制了侵袭和迁移，并降低了CRC细胞基质的黏附和扩散，这与miR-30b-5p过表达的结果一致。进一步的体内实验表明，miR-30b-5p的过表达抑制了CRCLM，但是Rap1b的抢救减弱了miR-30b-5p的抑制作用。此外，CRC标本中的miR-30b-5p被下调，Rap1b与原发性CRC和LM组织中的miR-30b-5p表达呈负相关。这些结果表明，miR-30b-5p通过靶向Rap1b起到转移抑制作用，并可能为CRCLM的治疗提供新的靶点。Rap1b与原发性CRC和LM组织中miR-30b-5p表达呈负相关。这些结果表明，miR-30b-5p通过靶向Rap1b起到转移抑制作用，并可能为CRCLM的治疗提供新的靶点。Rap1b与原发性CRC和LM组织中miR-30b-5p表达呈负相关。这些结果表明，miR-30b-5p通过靶向Rap1b起到转移抑制作用，并可能为CRCLM的治疗提供新的靶点。