Abstract
Up to date, miR-137 has been demonstrated as a tumor suppressor in many kinds of human malignancies. In the present study, we conducted transfection, western blot and RT-PCR to explore the role of miR-137 in the development of human glioblastoma (GBM). Here, we found that miR-137 expression was obviously down-regulated in GBM tissues and cells rather than matched non-tumor tissues and NHA cells. However, the expression of C-X-C motif ligand 12 (CXCL12) mRNA and protein were up-regulated in GBM tissues and cells. In vitro, miR-137 mimics inhibited GBM cell proliferation, migration and invasion, and the 3′-untranslated regions (3′-UTR) of CXCL12 were a direct target of miR-137. In addition, miR-137 mimics also inhibited the expression of EGFR, Bcl-2 and MMP2/9 proteins, but increased the expression of Bax protein. Notably, CXCL12 over-expression attenuated miR-137-inhibited cell proliferation and invasion, while CXCL12 siRNAs promoted miR-137 inhibition effects. In vivo, miR-137 mimics also suppressed tumor growth in nude mice xenograft model. In conclusion, miR-137 serves as a tumor suppressor by inhibition of CXCL12 in human GBM. Thus, miR-137-CXCL12 can be recommended as a useful and effective target for treatment of GBM.
Highlights
To date, human astrocytomas have been classified into four grades by The World Health Organization (WHO) based on tumor type [1,2,3,4]
We explored and detected the expression of miR-137 and C-X-C motif ligand 12 (CXCL12), and we investigated the role of miR-137 and CXCL12 on glioblastoma multiforme (GBM) cell proliferation, migration and invasion using in vitro assays, and elucidate the anticancer effects of miR-137
To figure out the role and significance of miR137 and CXCL12 in the development of GBM, we firstly detected the expression of miR-137 and CXCL12 in 50 cases of tumor tissues and paired adjacent nontumor tissues
Summary
Human astrocytomas have been classified into four grades by The World Health Organization (WHO) based on tumor type [1,2,3,4]. Grade IV astrocytoma is called as glioblastoma multiforme (GBM), which is the most common and malignant type of gliomas, and accounts for more than 60% of astrocytomas [5, 6]. Since the histopathological grade of gliomas can not reflect the pathological molecular mechanisms that drives the tumor biology, it is essential to seek a better diagnostic, prognostic and therapeutic target for GBM patients. In many kinds of human malignancies, miRNAs serves as oncogenes or tumor suppressor genes to regulate translation processes or mediate degradation of mRNAs according to the features of their targets [8]. CXCL12 has been reported to be involved into the development of glioblastoma [11,12,13]. The role of miR-137/CXCL12 in human GBM is still unknown
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