MicroRNAs have been confirmed to be a group of important regulators

MicroRNAs have been confirmed to be a group of important regulators during the pathogenesis of nasopharyngeal carcinoma (NPC). 6-10B cells and miR-92a silencing reduced the number of migrated and TAK-960 invaded 5-8F cells. Phosphatase and tensin homolog (PTEN) was confirmed as a direct downstream target of miR-92a in NPC cells. Normally alteration of miR-92a expression regulated PTEN/AKT pathway in NPC cells. Mechanistically miR-92a exerted its promoting effects around the metastatic actions of NPC cells through suppressing PTEN/AKT pathway. Taken together this study demonstrates that miR-92a is usually a encouraging prognostic biomarker for patients with NPC and may be a potential therapeutic target to prevent the metastasis of TAK-960 NPC. Keywords: microRNA-92a nasopharyngeal carcinoma PTEN signaling pathway tumor metastasis non-coding RNA head and neck neoplasms Introduction Nasopharyngeal carcinoma TAK-960 (NPC) which predominantly occurs in the southern part of the People’s Republic of China is usually a malignant epithelial tumor of the head and neck.1-3 Although amazing progress has been made in the therapeutic strategy of NPC the long-term survival of patients with NPC is still unsatisfactory. The major reasons for the poor prognosis of patients with NPC include local recurrence and systemic metastasis.4 5 Therefore it is of great importance to clarify the molecular mechanisms for the metastatic TAK-960 processes of NPC cells which may facilitate the development of novel therapeutic targets for NPC. MicroRNAs (miRNAs) is usually a group of short noncoding RNAs which regulate gene expression through mRNA cleavage and/or translation inhibition by binding to the 3′-untranslated region (3′-UTR) of the targeted mRNA.6 It can modulate various cellular processes including proliferation apoptosis movement and differentiation.7-9 And numerous studies have demonstrated that aberrant expression or dysfunction of miRNAs plays critical roles in the initiation CAGLP and progression of various human malignancies.10-12 Among numerous miRNAs microRNA-92a (miR-92a) which belongs to the cluster of miR-17-92 has been found to be a novel cancer-related miRNA. Abnormal expression and dysfunction of miR-92a have been found in hepatocellular carcinoma (HCC) 13 lung malignancy 14 colorectal malignancy 15 breast malignancy 16 and cervical malignancy.17 Increased level of miR-92a expression was confirmed in HCC 13 lung malignancy 14 and colorectal malignancy15 and was correlated with poor prognosis of patients with cancer. These results suggest that miR-92a plays an oncogenic role in human cancers. However studies of ovarian malignancy18 and breast cancer16 showed that this expression of miR-92a was downregulated TAK-960 indicating a tumor-suppressive function of miR-92a. These studies demonstrate that the exact biological role of miR-92a varies in different cancers. However the expression and functional role of miR-92a in NPC have never been examined before. In this study we found that miR-92a expression was elevated in NPC tissues and cells and increased expression of miR-92a was associated with poor prognosis of patients with NPC. Functionally we found that TAK-960 miR-92a could promote the migration and invasion of NPC cells. Furthermore phosphatase and tensin homolog (PTEN)/AKT pathway was recognized to be a direct functional downstream target of miR-92a. Materials and methods Clinical tissues and cell culture Eighty six freshly frozen NPC specimens and 20 normal nasopharyngeal epithelium specimens were obtained from the Department of Otorhinolaryngology Head and Neck Medical procedures the Second Affiliated Hospital of Xi’an Jiaotong University or college during January 2006 to December 2009. None of the patients received radiotherapy or chemotherapy before biopsy. Written informed consent was obtained from every patient. Table 1 shows the demographic features and clinicopathologic data. The ethics committee of Xi’an Jiaotong University or college approved all protocols including patients’ samples according to the Declaration of Helsinki (as revised in Tokyo 2004). Table 1 Correlation between the clinicopathologic characteristics and expression of miR-92a in NPC The human NPC cell lines CNE-1 CNE-2 5 and 6-10B were cultured in Roswell Park Memorial Institute-1640 (Invitrogen Carlsbad CA USA) supplemented with 5% fetal bovine serum (Gibco Grand Island NY USA) 100 U/mL penicillin and 100 U/mL streptomycin. The human immortalized nasopharyngeal epithelial cell lines NP69 were cultured in serum-free medium (Invitrogen) supplemented with.