Wang Xiaoli, Zhang Lili, Zhang Xingfeng, Xing Cuihong, Liu Ruidong, Zhang Fang
Department of Clinical Laboratory, Jinan City People's Hospital, Jinan People's Hospital Affiliated to Shandong First Medical University, Jinan, Shangdong, China.
Department of Clinical Laboratory, Yantaishan Hospital, Yantai, Shangdong, China.
Cancer Biomark. 2020;29(2):291-298. doi: 10.3233/CBM-201674.
Osteosarcoma (OS), aggressive neoplasms of the bone, is the most common primary bone cancer in children. MiR-196a usually low expressed in several tumors and its functions in osteosarcoma still unclear.
Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess the expression of miR-196a and the HOXA5. Cell metastasis and epithelial-mesenchymal transition (EMT) abilities were assessed using Transwell and western blot. The dual luciferase reporter assay was carried out to verify whether miR-196a directly targeted the 3'-untranslated region (UTR) of HOXA5 mRNA.
MiR-196a was overexpressed and HOXA5 was low expressed in osteosarcoma versus the non-tumor tissues and normal cell lines. Upregulation of miR-196a or downregulation of HOXA5 was associated with worse outcome of osteosarcoma patients. MiR-196a enhanced cell migration, invasion and EMT by regulating the expression of HOXA5 through directly targeting the 3'-UTR of its mRNA in osteosarcoma. HOXA5 partially reversed roles of miR-196a on metastasis and EMT in osteosarcoma.
MiR-196a promoted cell metastasis and EMT by targeting the 3'-UTR of HOXA5 mRNA in osteosarcoma. The newly identified miR-196a/HOXA5 axis provides novel insight into the pathogenesis of osteosarcoma.
骨肉瘤（OS）是一种侵袭性骨肿瘤，是儿童中最常见的原发性骨癌。MiR-196a在多种肿瘤中通常低表达，其在骨肉瘤中的功能仍不清楚。
采用定量实时聚合酶链反应（qRT-PCR）评估miR-196a和HOXA5的表达。使用Transwell和蛋白质免疫印迹法评估细胞转移和上皮-间质转化（EMT）能力。进行双荧光素酶报告基因检测以验证miR-196a是否直接靶向HOXA5 mRNA的3'非翻译区（UTR）。
与非肿瘤组织和正常细胞系相比，骨肉瘤中miR-196a过表达而HOXA5低表达。miR-196a上调或HOXA5下调与骨肉瘤患者的不良预后相关。在骨肉瘤中，miR-196a通过直接靶向HOXA5 mRNA的3'-UTR来调节其表达，从而增强细胞迁移、侵袭和EMT。HOXA5部分逆转了miR-196a在骨肉瘤转移和EMT中的作用。
在骨肉瘤中，miR-196a通过靶向HOXA5 mRNA的3'-UTR促进细胞转移和EMT。新发现的miR-196a/HOXA5轴为骨肉瘤的发病机制提供了新的见解。
