Liu Bo, Song Xiandong, Yan Zhaowei, Yang Hao, Shi Yingchao, Wu Jintao
Orthopedics Department Two, Hongqi Hospital, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China.
Department of Cardiology, Hongqi Hospital, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China.
Oncol Lett. 2019 Jan;17(1):781-788. doi: 10.3892/ol.2018.9711. Epub 2018 Nov 15.
Increasing evidence has suggested that microRNAs (miRNAs; miRs) are extensively involved in the progression of chondrosarcoma (CHS). However, few studies have investigated the functional role of miR-525 in CHS tissues and cells. In the present study, it was discovered that miR-525 levels were decreased in CHS tissues and cells. Dual luciferase assays indicated that F-spondin 1 (SPON1) is a target gene of microRNA (miR)-525. In addition, miR-525 overexpression suppressed SW1353 cell migration and invasion and enhanced SW1353 cell apoptosis. Increased SPON1 expression levels were identified in CHS tissues and cell lines. Furthermore, miR-525 overexpression significantly suppressed the activation of focal adhesion kinase (FAK)/Src/phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt) signaling in CHS cells; this suppression led to SPON1 silencing. In comparison, the SPON1 knockdown-mediated inactivation of FAK/Src/PI3K/Akt signaling was inhibited by inhibiting miR-525. In summary, the present study revealed that decreased miR-525 levels could enhance CHS malignancy as decreased miR-525 binding to the 3' untranslated region of SPON1 activates FAK/Src/PI3K/Akt signaling.
越来越多的证据表明，微小RNA（miRNA；miR）广泛参与软骨肉瘤（CHS）的进展。然而，很少有研究调查miR-525在CHS组织和细胞中的功能作用。在本研究中，发现CHS组织和细胞中miR-525水平降低。双荧光素酶测定表明，F-腱蛋白1（SPON1）是微小RNA（miR）-525的靶基因。此外，miR-525过表达抑制SW1353细胞迁移和侵袭，并增强SW1353细胞凋亡。在CHS组织和细胞系中鉴定出SPON1表达水平升高。此外，miR-525过表达显著抑制CHS细胞中粘着斑激酶（FAK）/Src/磷脂酰肌醇-4,5-二磷酸3-激酶（PI3K）/蛋白激酶B（Akt）信号通路的激活；这种抑制导致SPON1沉默。相比之下，抑制miR-525可抑制SPON1敲低介导的FAK/Src/PI3K/Akt信号通路失活。总之，本研究表明，miR-525水平降低可增强CHS的恶性程度，因为miR-525与SPON1的3'非翻译区结合减少会激活FAK/Src/PI3K/Akt信号通路。
