Hsieh Mingli, Huang Pei-Ju, Chou Pei-Yu, Wang Shih-Wei, Lu Hsi-Chi, Su Wei-Wen, Chung Yuan-Chiang, Wu Min-Huan
Department of Life Science, Tunghai University, No. 1727, Sec. 4, Taiwan Boulevard, Taichung 407, Taiwan.
Life Science Research Center, Tunghai University, No. 1727, Sec. 4, Taiwan Boulevard, Taichung 407, Taiwan.
Biomedicines. 2022 Apr 29;10(5):1030. doi: 10.3390/biomedicines10051030.
Carbonic anhydrase VIII (CAVIII) is a member of the CA family, while CA8 is the oncogene. Here we observed increased expression of CAVIII with high expression in colorectal cancer tissues. CAVIII is also expressed in more aggressive types of human colorectal cancer cells. Upregulated CAVIII expression in SW480 cell lines increased vascular endothelial growth factor (VEGF) and reduced miRNA16-5p. Conversely, knockdown of the CAVIII results in VEGF decline by up-regulated miRNA16-5p. Moreover, the collection of different grades of CAVIII expression CRC cells supernatant co-culture with endothelial progenitor cells (EPCs) promotes the ability of tube formation in soft agar and migration in the Transwell experiment, indicating that CAVIII might facilitate cancer-cell-released VEGF via the inhibition of miRNA16-5p signaling. Furthermore, in the xenograft tumor angiogenesis model, knockdown of CAVIII significantly reduced tumor growth and tumor-associated angiogenesis. Taken together, our results prove that the CAVIII/miR-16-5p signaling pathway might function as a metastasis suppressor in CRC. Targeting CAVIII/miR-16-5p may provide a strategy for blocking its metastasis.
碳酸酐酶VIII（CAVIII）是碳酸酐酶（CA）家族的一员，而CA8是一种癌基因。在此，我们观察到CAVIII在结直肠癌组织中高表达，其表达增加。CAVIII在侵袭性更强的人类结肠癌细胞类型中也有表达。SW480细胞系中CAVIII表达上调会增加血管内皮生长因子（VEGF）并降低miRNA16 - 5p。相反，敲低CAVIII会导致VEGF因miRNA16 - 5p上调而下降。此外，收集不同CAVIII表达水平的结直肠癌细胞上清液与内皮祖细胞（EPCs）共培养，在软琼脂中促进了管形成能力，在Transwell实验中促进了迁移能力，这表明CAVIII可能通过抑制miRNA16 - 5p信号传导来促进癌细胞释放的VEGF。此外，在异种移植肿瘤血管生成模型中，敲低CAVIII显著降低了肿瘤生长和肿瘤相关血管生成。综上所述，我们的结果证明CAVIII/miR - 16 - 5p信号通路可能在结直肠癌中作为一种转移抑制因子发挥作用。靶向CAVIII/miR - 16 - 5p可能为阻断其转移提供一种策略。
