Department of Orthopedics, Shantou Chaonan Minsheng Hospital, Shantou, China
Department of Orthopedics, Chaoyang Distric, Shantou City, Dafeng Hospital, Shantou, China.
Biosci Rep. 2019 Feb 8;39(2). doi: 10.1042/BSR20181283. Print 2019 Feb 28.
Having a better grasp of the molecular mechanisms underlying carcinogenesis and progression in osteosarcoma would be helpful to find novel therapeutic targets. Different types of cancers have presented abnormal expression of miRNA-101 (miR-101). Nevertheless, we still could not figure out what expression of miR-101 in human osteosarcoma is and its biological function. Thus, we conducted the present study to identify its expression, function, and molecular mechanism in osteosarcoma. We detected the expression of miR-101 in osteosarcoma samples and cell lines. The effects of miR-101 on osteosarcoma cells' proliferation and invasion were evaluated. Luciferase reporter assay was applied to identify the direct target of miR-101. Compared with adjacent normal specimens and normal bone cell line by using qPCR, the expression levels of miR-101 in osteosarcoma specimens and human osteosarcoma cell lines distinctly decreased. According to function assays, we found that overexpression of miR-101 significantly inhibited the cell proliferation and invasion in osteosarcoma cells. Moreover, we confirmed that zinc finger E-box binding homeobox 2 (ZEB2) was a direct target of miR-101. In addition, overexpression of ZEB2 could rescue the inhibition effect of proliferation and invasion induced by miR-101 in osteosarcoma cells. MiR-101 has been proved to be down-regulated in osteosarcoma and has the ability to suppress osteosarcoma cell proliferation and invasion by directly targetting ZEB2.
更好地掌握骨肉瘤发生和进展的分子机制将有助于寻找新的治疗靶点。不同类型的癌症表现出 miRNA-101（miR-101）的异常表达。然而，我们仍然不清楚 miR-101 在人骨肉瘤中的表达情况及其生物学功能。因此，我们进行了本研究，以确定其在骨肉瘤中的表达、功能和分子机制。我们检测了骨肉瘤样本和细胞系中 miR-101 的表达。评估了 miR-101 对骨肉瘤细胞增殖和侵袭的影响。应用荧光素酶报告基因检测鉴定 miR-101 的直接靶标。通过 qPCR 与相邻正常标本和正常骨细胞系相比，骨肉瘤标本和人骨肉瘤细胞系中 miR-101 的表达水平明显降低。根据功能测定，我们发现过表达 miR-101 可显著抑制骨肉瘤细胞的增殖和侵袭。此外，我们证实锌指 E 盒结合同源盒 2（ZEB2）是 miR-101 的直接靶标。此外，过表达 ZEB2 可挽救 miR-101 诱导的骨肉瘤细胞增殖和侵袭抑制作用。miR-101 在骨肉瘤中被证明下调，通过直接靶向 ZEB2 抑制骨肉瘤细胞的增殖和侵袭。
