MiR-4310 induced by SP1 targets PTEN to promote glioma progression
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Cancer Cell International Open Access
PRIMARY RESEARCH
MiR‑4310 induced by SP1 targets PTEN to promote glioma progression Zhiyong Wu1,5† , Jie Luo1†, Tengyue Huang2†, Renhui Yi2, Shengfeng Ding1, Cheng Xie1, An’qi Xu1, Yu Zeng3, Xizhao Wang4, Ye Song1, Xiaofeng Shi5* and Hao Long1*
Abstract Background: miRNAs have been reported to be involved in multiple biological processes of gliomas. Here, we aimed to analyze miR-4310 and its correlation genes involved in the progression of human glioma. Methods: miR-4310 expression levels were examined in glioma and non-tumor brain (NB) tissues. The molecular mechanisms of miR-4310 expression and its effects on cell proliferation, migration, and invasion were explored using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide, Transwell chamber, Boyden chamber, and western blot analyses, as well as its effect on tumorigenesis was explored in vivo in nude mice. The relationships between miR4310, SP1, phosphatase, and tensin homolog (PTEN) were explored using chromatin immunoprecipitation, agarose gel electrophoresis, electrophoresis mobility shift, and dual-luciferase reporter gene assays. Results: miR-4310 expression was upregulated in glioma tissues compared to that in NB tissues. Overexpressed miR-4310 promoted glioma cell proliferation, migration, and invasion in vitro, as well as tumorigenesis in vivo. The inhibition of miR-4310 expression was sufficient to reverse these results. Mechanistic analyses revealed that miR4310 promoted glioma progression through the PI3K/AKT pathway by targeting PTEN. Additionally, SP1 induced the expression of miR-4310 by binding to its promoter region. Conclusion: miR-4310 promotes the progression of glioma by targeting PTEN and activating the PI3K/AKT pathway; meanwhile, the expression of miR-4310 was induced by SP1. Keywords: miR-4310, SP1, PTEN, PI3K/AKT signaling, Glioma Background Glioma is the most common primary intraparenchymal central nervous system (CNS) tumor. Brain tumors are classified according to the World Health Organization (WHO) CNS tumor grading system. In the revised 2016 WHO classification of CNS tumors, numerous molecular *Correspondence: [email protected]; [email protected] † Zhiyong Wu, Jie Luo and Tengyue Huang contributed equally to this work 1 Department of Neurosurgery, Nanfang Hospital, Southern Medical University, 510515 Guangzhou, Guangdong, People’s Republic of China 5 Department of Neurosurgery, Shenzhen Longgang Central Hospital (The Second Affiliated Hospital of the Chinese University of Hong Kong ((Shenzhen)), Shenzhen 518116, Guangdong, People’s Republic of China Full list of author information is available at the end of the article
markers (IDH, 1p/19q codeletion, H3 Lys27Met, and RELA-fusion) are used in combination with histology for pathological diagnosis [1–4]. Although we now have a more accurate diagnosis of glioma, the prognosis for patients with malignant glioma remains very poor since less than 5% of them have a 5 year relative survival [5]. PTEN is a common tumor suppressor gene. Th
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