Tumor-suppressive effects of miR-29c on gliomas

Abstract

Although miR-29c has been shown to be expressed less in various kinds of solid cancers, its expression pattern and tumor-suppressive effects in gliomas remain largely unknown. In this study, we detected miR-29c in 10 nontumoral brain tissues and 60 gliomas of various grades and found that its labeling indexes were significantly lower in gliomas (53.7% for the nontumoral brain tissues, and 18.9, 5.5, and 1.8% for the WHO grade I-II, grade III, and grade IV glioma groups, respectively). We then overexpressed miR-29c in the SNB19 glioblastoma cell line and found that it markedly downregulated the expression level of CDK6, and accordingly increased the percentage of the tumor cells in the G1 phase from 44.5 to 69.1% and decreased the colony formation efficiency from 81.1 to 51.5%. miR-29c overexpression also increased the percentage of apoptotic cells from 27.2 to 54.8%, and led to a more than 50% decrease in the migratory and invasive abilities of the tumor cells. Our study shows that miR-29c can effectively block the proliferation of glioblastoma cells by inducing G1 arrest, promote their apoptosis, and inhibit their migration and invasion. At least some of its tumor-suppressive effects are mediated by specifically downregulating the expression of CDK6. Therefore, miR-29c can be used as a tumor suppressor in the gene therapy of malignant gliomas.

miR-29s inhibit the malignant behavior of U87MG glioblastoma cell line by targeting DNMT3A and 3B

“…The anti-glioma effects of some miR-29 family members as well as the related targets such as CDK6, MMP-2 and VEGF have been reported in several GBM cell lines [8,15]. We herein reconfirmed that all miR-29 family members effectively halted the proliferation, migration and invasion of U87MG cells and induced their apoptosis.…”

“…The mature members of human miR-29 family, including miR29a-c, are expressed at aberrantly low levels in a variety of tumors including GBM [2][3][4][5][6][7][8]. Increasing evidence associates low miR29s expression with tumorigenesis and progression, indicating the tumor suppressive nature of these miRNAs.…”

MiR-29c inhibits cell growth, invasion, and migration of pancreatic cancer by targeting ITGB1

“… 9 MiR-29c is a member of the miR-29 family, and has been reported to be deregulated in many different types of cancer. 10 – 12 MiR-29c is frequently silenced or downregulated in many kinds of cancers, including hepatocellular cancer, 13 , 14 nasopharyngeal cancer, 15 glioma, 16 , 17 gastric cancer, 18 , 19 bladder cancer, 20 and colorectal cancer, 21 and in those cancers, miR-29c usually has tumor-suppressive effects, while the expression levels of miR-29c in osteosarcoma tissues and patients’ sera are all significantly higher than those in normal controls. 22 In PC, recent reports have shown that miR-29c suppresses PC liver metastasis in a nude mouse model and affects patient survival, 23 and reduction of miR-29c enhances PC cell migration and stem cell-like phenotype.…”

Inhibition of miR-29c promotes proliferation, and inhibits apoptosis and differentiation in P19 embryonic carcinoma cells

“…Nguyen et al ( 18 ) found that low levels of miR-29c were associated with the progression of melanoma, and Wang et al ( 19 ) identified an inhibitory role in hepatocellular carcinoma. Other investigations have revealed that miR-29c is involved in leukemia ( 20 ), glioma ( 21 ), bladder cancer ( 22 ) and nasopharyngeal ( 23 ) and gastric carcinoma ( 24 ). Taken together, it has become apparent that a common feature of tumorigenesis is the downregulation of miR-29c, and that the presence of miR-29c inhibits tumor cell growth, which may be indicative of improved prognosis.…”