Glioblastoma multiforme (GBM) is the most aggressive tumor in the brains, which is derived from neural stem cell or glial progenitor cells. Although the chemotherapy and radiotherapy are general treatments to reduce the tumor growth, patients with GBM have a percentage of survival below 18 months after treatments. Therefore, the study to dissect the function of molecules in GBM growth is important. MicroRNA-34a (miR-34a) is a small non-coding RNA molecule, and it is a known tumor inhibitor. A growing body of the studies have reported that miR-34a expression was downregulated in many cancer types, such as lung cancer, breast cancer, and glioma. Overexpression of miR-34a can inhibit significantly the tumorigenic activities of these tumor cells. In addition, our previous study has also shown that interleukin 33 (IL-33) was expressed abundantly in high tumorigenic rat glioma cell line (C6-1) compared to less tumorigenic C6 glioma cell line (C6-2). The downregulation of IL-33 in C6-1 cells can effectively suppress C6-1 cell proliferation. In this study, we found that miR-34a was expressed at the lower level in high tumorigenic rat glioma cell line (C6-1) than that detected in less tumorigenic C6 glioma cell line (C6-2). Moreover, lentivirus-mediated overexpression of miR-34a in C6-1 cells can significantly suppressed C6-1 cell proliferation and colony formation, as well as their cell invasion and migratory abilities. However, miR-34a overexpression caused the upregulation of interleukin-33 (IL-33). We have previously found that IL-33 was abundantly expressed in C6-1 cells and promoted C6-1 cell growth. Thus, our further experiments were to examine if lentivirus-mediated shRNA targeting IL-33 to knockdown IL-33 expression (IL-33KD) with miR-34a overexpression can exert more effective inhibition in C6-1 cell growth. The results showed that IL-33KD and miR-34a overexpression induced more efficient inhibition in cell growth, colony formation, cell invasion, and cell migration of C6-1 cells. Collectively, our findings provide important evidence that an increase in IL-33 expression induced by the upregulation of miR-34a might reduce miR-34a-mediated effect on the inhibition of rat glioma cell growth. The combinatorial approach of miR-34a upregulation with IL-33 downregulation can be a better strategy to reduce glioma cell growth.
Keywords: mir-34a, IL-33, Glioblastoma.

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