Department of Colorectal Anal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Alberta Institute, Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China.
Biochem Biophys Res Commun. 2022 Jun 18;609:119-126. doi: 10.1016/j.bbrc.2022.04.006. Epub 2022 Apr 5.
Colorectal cancer (CRC) is a common malignant tumor of digestive tract, but the molecular mechanism of its occurrence and development is not clear. Some studies have shown that microRNA (miRNA) plays an important role in the occurrence and development of cancer, but many miRNAs which play an important role in the progression of CRC remain to be investigated. In this study，we found that the expression of miR-1538 was significantly down-regulated in CRC tissues and cells, and its expression level was significantly correlated with tumor size, clinical stage and prognosis. Functional and mechanism experiments showed that miR-1538 decreased the protein level of DNA methyltransferases 3A (DNMT3A) and inhibited the proliferation, migration and invasion of CRC cells by targeting the 3'-UTR of DNMT3A mRNA. Our results identify the biological function and mechanism of miR-1538 as a tumor suppressor gene in the progression of CRC, and suggest that miR-1538 can be used as a potential prognostic marker and therapeutic target for CRC.
结直肠癌（CRC）是一种常见的消化道恶性肿瘤，但它的发生和发展的分子机制尚不清楚。一些研究表明，微小 RNA（miRNA）在癌症的发生和发展中起着重要作用，但许多在 CRC 进展中起重要作用的 miRNAs 仍有待研究。在本研究中，我们发现 miR-1538 在 CRC 组织和细胞中的表达明显下调，其表达水平与肿瘤大小、临床分期和预后显著相关。功能和机制实验表明，miR-1538 通过靶向 DNMT3A mRNA 的 3'-UTR 降低 DNA 甲基转移酶 3A（DNMT3A）的蛋白水平，并抑制 CRC 细胞的增殖、迁移和侵袭。我们的研究结果确定了 miR-1538 作为 CRC 进展中的肿瘤抑制基因的生物学功能和机制，并表明 miR-1538 可作为 CRC 的潜在预后标志物和治疗靶点。
