Zheng Hailun, Ma Renqiang, Wang Qizhi, Zhang Pei, Li Dapeng, Wang Qiangwu, Wang Jianchao, Li Huabin, Liu Hao, Wang Zhiwei
Department of Gastroenterology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China.
Cancer Center, ENT Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Oncotarget. 2015 Sep 29;6(29):27805-15. doi: 10.18632/oncotarget.4738.
MicroRNAs (miRNAs) play a critical role in controlling tumor invasion and metastasis via regulating the expression of a variety of targets, which act as oncogenes or tumor suppressor genes. Abnormally expressed miR-625-3p has been observed in several types of human cancers. However, the molecular mechanisms of miR-625-3p-mediated tumorigenesis are largely elusive. Therefore, the aim of this study was to evaluate the biological function and molecular insight on miR-625-3p-induced oncogenesis in colorectal carcinoma (CRC). The effects of miR-625-3p in cell migration and invasion were analyzed by wound healing assay and transwell assay, respectively. In addition, the expression of miR-625-3p and its targets was detected in five human CRC cell lines. In the present study, we found that overexpression of miR-625-3p promoted migration and invasion in SW480 cells, whereas downregulation of miR-625-3p inhibited cell motility in SW620 cells. More importantly, we observed potential binding sites for miR-625-3p in the 3'-untranslated region of suppressor of cancer cell invasion (SCAI). Notably, we identified that overexpression of miR-625-3p inhibited the expression of SCAI, while depletion of miR-625-3p increased SCAI level, suggesting that SCAI could be a target of miR-625-3p. Additionally, we revealed that miR-625-3p exerts its oncogenic functions through regulation of SCAI/E-cadherin/MMP-9 pathways. Our findings indicate the pivotal role of miR-625-3p in invasion that warrants further exploration whether targeting miR-625-3p could be a promising approach for the treatment of CRC.
微小RNA（miRNA）通过调控多种充当癌基因或肿瘤抑制基因的靶标的表达，在控制肿瘤侵袭和转移中发挥关键作用。在几种人类癌症中已观察到miR-625-3p表达异常。然而，miR-625-3p介导肿瘤发生的分子机制在很大程度上仍不清楚。因此，本研究的目的是评估miR-625-3p在结直肠癌（CRC）中诱导肿瘤发生的生物学功能和分子机制。分别通过伤口愈合试验和Transwell试验分析了miR-625-3p对细胞迁移和侵袭的影响。此外，在五种人类CRC细胞系中检测了miR-625-3p及其靶标的表达。在本研究中，我们发现miR-625-3p的过表达促进了SW480细胞的迁移和侵袭，而miR-625-3p的下调抑制了SW620细胞的运动能力。更重要的是，我们在癌细胞侵袭抑制因子（SCAI）的3'-非翻译区观察到了miR-625-3p的潜在结合位点。值得注意的是，我们发现miR-625-3p的过表达抑制了SCAI的表达，而miR-625-3p的缺失增加了SCAI的水平，这表明SCAI可能是miR-625-3p的一个靶标。此外，我们还发现miR-625-3p通过调节SCAI/E-钙黏蛋白/MMP-9信号通路发挥其致癌功能。我们的研究结果表明miR-625-3p在侵袭中起关键作用，这值得进一步探索靶向miR-625-3p是否可能是治疗CRC的一种有前景的方法。
