Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, PR China.
J Cell Biochem. 2019 Nov;120(11):18629-18639. doi: 10.1002/jcb.28874. Epub 2019 Jul 24.
Colorectal cancer is considered as the fourth leading reason of cancer-linked deaths worldwide. However, our knowledge about its pathogenic mechanism remains inadequate. MicroRNA 32 (miR-32), a member of small noncoding RNAs, has been found vital roles in tumorigenesis. This study studied its functions and underlying mechanism in colorectal cancer. The experiment revealed the obvious upregulation of miR-32 in colorectal cancer tissues and six cancer cell lines, compared with normal tissues and cells. Moreover, miR-32 upregulation reduced cell apoptosis and promoted cell proliferation and migration, while its downregulation displayed opposite effects. Dual luciferase reporter assays proved that miR-32 bound to the 3'-untranslated region (3'-UTR) of OTU domain containing 3 (OTUD3), suggesting that miR-32 directly targeted OTUD3. Further experiments demonstrated that overexpression of miR-32 could reduce the expression level of OTUD3. Furthermore, OTUD3 silence promoted proliferation and motility and decreased apoptosis for HCT116 cells and restored partly miR-32-mediated cell proliferation, migration, and antiapoptosis for colon cancer. Therefore, our study indicated that miR-32 enhanced cell proliferation and motility abilities, and inhibited apoptosis by directly targeting OTUD3 in colon cancer cells, which implied that miR-32 was hopeful to be a biomarker or target used for diagnosis and therapy of colon cancer.
结直肠癌被认为是全球癌症相关死亡的第四大原因。然而，我们对其发病机制的了解仍然不足。微小 RNA 32（miR-32）是小非编码 RNA 的成员，已被发现其在肿瘤发生中具有重要作用。本研究探讨了 miR-32 在结直肠癌中的功能及其潜在机制。实验结果表明，与正常组织和细胞相比，结直肠癌组织和六种癌细胞系中 miR-32 的表达明显上调。此外，miR-32 的上调降低了细胞凋亡，促进了细胞增殖和迁移，而其下调则显示出相反的效果。双荧光素酶报告基因实验证实 miR-32 与含有 OTU 结构域的 3（OTUD3）的 3'非翻译区（3'-UTR）结合，表明 miR-32 直接靶向 OTUD3。进一步的实验表明，miR-32 的过表达可以降低 OTUD3 的表达水平。此外，OTUD3 沉默促进了 HCT116 细胞的增殖和迁移，减少了凋亡，并部分恢复了 miR-32 介导的结肠癌细胞增殖、迁移和抗凋亡。因此，我们的研究表明，miR-32 通过直接靶向 OTUD3 增强了结肠癌细胞的增殖和迁移能力，并抑制了凋亡，这意味着 miR-32 有望成为诊断和治疗结肠癌的生物标志物或靶标。
