Abstract
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.
Highlights
Osteosarcoma is one of the most common primary malignant bone tumors and it accounts for approximately one-fifth of all primary bone cancers worldwide [1,2]
MiR-101 was significantly down-regulated in osteosarcoma cell lines compared with human osteoblast cell line HOB-c (Figure 1C)
It was found that the miR-101 expression level was correlated with tumor stage and metastatic status
Summary
Osteosarcoma is one of the most common primary malignant bone tumors and it accounts for approximately one-fifth of all primary bone cancers worldwide [1,2]. It is urgent to excavate the molecular mechanisms for osteosarcoma progression and discover the potential molecular markers for tumor-targetted therapy. MiRNA has been proposed as a novel target for anticancer therapy in recent years [7,8]. By means of directly targetting oncogenes or tumor suppressor genes, no less than 50% of miRNAs are found to be involved in human tumorigenesis [9,10]. MiR-451 inhibits tumor growth, migration, and angiogenesis by way of directly targetting IL-6R in osteosarcoma [11]. MiR-27a is able to promote osteosarcoma cells proliferation, migration, and invasion via MAP2K4 [12]. We have learnt that miR-101 is significantly down-regulated and mainly serves as a tumor suppressor in various human cancers. One specific miRNA might act in different roles including oncogene or tumor
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