Downregulation of miR-383 promotes glioma cell invasion by targeting insulin-like growth factor 1 receptor
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ORIGINAL PAPER
Downregulation of miR-383 promotes glioma cell invasion by targeting insulin-like growth factor 1 receptor Zhanwen He • Danyang Cen • Xiangyang Luo Dongfang Li • Pinggan Li • Liyang Liang • Zhe Meng
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Received: 4 March 2013 / Accepted: 21 March 2013 / Published online: 6 April 2013 Ó Springer Science+Business Media New York 2013
Abstract Invasiveness is a major clinical feature of glioma, an aggressive brain tumor with poor prognosis. Although there is emerging evidence that some microRNAs are involved in the glioma cell invasion process, it remains necessary to find functional microRNAs and elucidate the underlying molecular mechanisms. Here, we reported that a microRNA, miR-383, was downregulated in gliomas and inversely correlated with glioma pathological grades. Downregulation of miR-383 enhanced, whereas upregulation of miR-383 inhibited, the glioma cell invasive ability. Furthermore, we found that downregulation of miR-383 activated the AKT signaling following upregulation of MMP2 expression by directly targeting insulinlike growth factor 1 receptor (IGF1R). Importantly, we demonstrated that IGF1R expression is critical for miR-383 downregulation-induced cell invasion. Taken together, these findings uncover a novel regulatory mechanism for constitutive IGF1R signaling activation in glioma cancer and may provide miR-383 as a useful diagnostic marker or therapeutic target. Keywords
miR-383 Glioma Invasion IGF1R
Zhanwen He and Danyang Cen contributed equally to this work. Z. He (&) X. Luo D. Li P. Li L. Liang Z. Meng Department of Paediatrics, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan Jiang West Road, Guangzhou 510120, Guangdong, People’s Republic of China e-mail: [email protected] D. Cen Clinical department of the University, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, People’s Republic of China
Instruction Gliomas make up *30 % of all brain and central nervous system tumors and 80 % of all malignant brain tumors [1]. Gliomas are rarely curable. The cumulative 2-year survival rate is \25 %, and the median survival time of the grade 4 glioma, glioblastoma multiforme, is less than 12 months [2–4]. Such poor prognosis of malignant gliomas is largely attributed to a high tendency to diffusely infiltrate and migrate into surrounding brain tissue [5, 6]. Several major acquired genetic mutations, including p53, PTEN and EGFR, have been found in glioma progression [7]. However, the microRNA-involved mechanisms are still unclear and remain to be elucidated. Thus, exploring functional microRNAs and delineate the mechanisms that regulate the glioma invasion might allow the identification of novel targets for prognosis and therapeutic intervention. The type 1 insulin-like growth factor (IGF) receptor (IGF1R) signaling is constitutively activated in various types of human cancer, including lung, breast, prostate and glioma cancers [8–11]. Meanwhile, IGF1R has been demonstrated to play critical roles in multiple biological processes of t
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