Suppression of miR-184 in malignant gliomas upregulates SND1 and promotes tumor aggressiveness
| العنوان: | Suppression of miR-184 in malignant gliomas upregulates SND1 and promotes tumor aggressiveness |
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| المؤلفون: | Bin Hu, Devanand Sarkar, Mitchell E. Menezes, Mohammad A. Alzubi, Swadesh K. Das, Luni Emdad, Aleksandar Janjic, Paul B. Fisher, Xue-Ning Shen, Prasanna K. Santhekadur |
| المصدر: | Neuro-Oncology. 17:419-429 |
| بيانات النشر: | Oxford University Press (OUP), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Cancer Research, SND1, Kaplan-Meier Estimate, Biology, Mice, Cell Line, Tumor, Glioma, microRNA, Gene expression, medicine, Animals, Humans, Neoplasm Invasiveness, Brain Neoplasms, Nuclear Proteins, Aggressive cancer, Endonucleases, medicine.disease, Up-Regulation, MicroRNAs, Gene Expression Regulation, Oncology, Cell culture, Basic and Translational Investigations, Disease Progression, Cancer research, Neurology (clinical), Cancer development |
| الوصف: | Malignant glioma is an aggressive cancer requiring new therapeutic targets. MicroRNAs (miRNAs) regulate gene expression post transcriptionally and are implicated in cancer development and progression. Deregulated expressions of several miRNAs, specifically hsa-miR-184, correlate with glioma development.Bioinformatic approaches were used to identify potential miR-184-regulated target genes involved in malignant glioma progression. This strategy identified a multifunctional nuclease, SND1, known to be overexpressed in multiple cancers, including breast, colon, and hepatocellular carcinoma, as a putative direct miR-184 target gene. SND1 levels were evaluated in patient tumor samples and human-derived cell lines. We analyzed invasion and signaling in vitro through SND1 gain-of-function and loss-of-function. An orthotopic xenograft model with primary glioma cells demonstrated a role of miR-184/SND1 in glioma pathogenesis in vivo.SND1 is highly expressed in human glioma tissue and inversely correlated with miR-184 expression. Transfection of glioma cells with a miR-184 mimic inhibited invasion, suppressed colony formation, and reduced anchorage-independent growth in soft agar. Similar phenotypes were evident when SND1 was knocked down with siRNA. Additionally, knockdown (KD) of SND1 induced senescence and improved the chemoresistant properties of malignant glioma cells. In an orthotopic xenograft model, KD of SND1 or transfection with a miR-184 mimic induced a less invasive tumor phenotype and significantly improved survival of tumor bearing mice.Our study is the first to show a novel regulatory role of SND1, a direct target of miR-184, in glioma progression, suggesting that the miR-184/SND1 axis may be a useful diagnostic and therapeutic tool for malignant glioma. |
| تدمد: | 1523-5866 1522-8517 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bbb932cd3fc87e9b63b9c8aa0ae04f25Test https://doi.org/10.1093/neuonc/nou220Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bbb932cd3fc87e9b63b9c8aa0ae04f25 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15235866 15228517 |
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