Human miR-31 targets radixin and inhibits migration and invasion of glioma cells

Abstract

Abstract. MicroRNAs (miRNAs) are a novel group of short RNAs, about 20-22 nucleotide in length, that regulate gene expression in a post-transcriptional manner by affecting the stability or translation of mRNAs and play important roles in many biological processes. Many microRNAs have been implicated in glioblastoma. miR-31 is dysregulated in several types of cancer including colon, breast, prostate, gastric and lung cancers. However, the expression and role of miR-31 in glioblastoma are still unclear. In this study, we performed real-time reverse transcriptase polymerase chain reaction (RT-PCR) assays on 10 glioblastoma and 7 normal brain tissues. We found that miR-31 is down-regulated in glioblastoma compared with normal brain tissues. Ectopic expression of miR-31 inhibited migration and invasion ability of U251 glioma cells. Expression profiling analysis revealed that miR-31 affected the cell migration and motility process by regulating migration and invasion related genes. Finally, we demonstrated that miR-31 targeted radixin predominantly via inhibition of protein translation instead of degradation of mRNA. IntroductionThe annual incidence of malignant glioma is approximately 5 cases per 100,000 people [Central Brain Tumor Registry of the Unites States (CBTRUS) 2009 statistical report, www.cbtrus. org]. Despite aggressive surgery, radiation and chemotherapy, the median survival is only 12-15 months for glioblastoma (GBM) (1). Better understanding of the mechanism and finding new therapeutic targets for glioma is urgent. miRNAs are a novel group of short RNAs, about 20-22 nucleotide in length, that regulate gene expression in a post-transcriptional manner by affecting the stability or translation of mRNAs (2). Many microRNAs have been implicated in glioblastoma (3,4). Ciafr et al examined the global expression levels of 245 microRNAs in glioblastoma multiforme by microarray and identified a group of miRNAs including a strongly up-regulated expression of miR-221 and down-regulated expression of a set of brain-enriched miRNAs including miR-128, miR181a, miR-181b and miR-181c in glioblastoma (5). miR-31 expression was down-regulated in human carcinomas of the breast (6), prostate (7), ovary (8) and stomach (9), but paradoxically up-regulated in human colorectal (10), liver (11), head-and-neck tumors (12) and squamous cell carcinomas of the tongue (13). It can either elicit promoting or inhibitive effects on cancers depending on the organs where the cancers arise. In breast cancer, miR-31 inhibits metastasis by targeting ITGAR, RDX and RhoA (6); but in lung cancer, miR-31 acts as an oncogenic miRNA by repressing tumor suppressor LATS2 and PPP2R2A (14). In colon carcinoma cells, miR-31 expression is regulated by TGF-β and it targets TIAM1 to regulate migration and invasion (15). However, the role of miR-31 in GBM has not been studied, and which of the targets identified in other cancer types are used by GBM cells remains unknown.In this study, we confirmed underexpression of miR-31 in glioblastoma samples compared...

NF-κB and STAT3 in glioblastoma: therapeutic targets coming of age

“…Presently, there are few tumor suppressive miRs associated with NF-κB signaling in GBM. However, we and others have found that miR-31 is largely downregulated or absent in GBM [58, 59] and this occurrence predominates in the Classical and Mesenchymal subtypes of GBM (unpublished observation). Moreover, reduced miR-31 levels are part of a ten miR expression signature that independently predicts patient survival [60].…”

Radixin Enhances Colon Cancer Cell Invasion by Increasing MMP-7 Production via Rac1-ERK Pathway

“…Our results showed that the expression of radixin was increased in colon cancer cells, further confirming a role of radixin in colon cancer. Experimental studies have revealed that radixin contributes to the invasion and metastasis of gastric cancer cells and glioma cells [18, 19], and silencing of radixin inhibited the invasion and growth of pancreatic cancer cells in vitro and in vivo [20]. However, little is known about the function of radixin in colon cancer.…”

Dysregulation of NEUROG2 plays a key role in focal cortical dysplasia

“…Furthermore, we have also shown that hsa‐miR‐31 is significantly downregulated in FCD type II. The decreased expression of miR‐31 was detected in glioblastoma,48 and it is believed that miR‐31 may be an oncogene, because it represses tumor suppressor genes, and acts in cell migration and motility by regulating the gene radixin 49…”