Int j oncol. Bcl2. Moreover, miR-134 inhibited cellular migration and invasiveness through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene was AZD7762 revealed to be a putative target of miR-134, which was inversely correlated with miR-134 expression in NSCLC. Taken together, our results demonstrated that miR-134 played a pivotal role on NSCLC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic gene, and is an important oncogene that shown strong power of oncogenicity, by promotion of cell growth, migration, invasion and epithelial mesenchymal transition (EMT), as well as inhibition of cell apoptosis in many tumors including lung cancer [39C41]. Here, we reported that miR-134 is indeed suppressed in primary lung cancers compared with the matching adjacent normal tissues, and found 3-UTR of the human CCND1 mRNA is really a target of miR-134. Collectively, we discovered that miR-134 inhibited NSCLC cell prolifferation, colony formation, migration and invasion, and promoted cell apoptosis by targeting 3-UTR of = 0.0003), smoking history (= 0.0001), TNM stage (= 0.0314), and lymph node metastasis (= 0.0154). However, miR-134 expression was not correlated with other clinical characteristics such as differentiation (= 0.1713), gender = 0.7062), age (= 0.4877) or histological tumor type (= 0.5273) in NSCLC (Table ?(Table1).1). Additionally, KaplanCMeier survival analysis demonstrated that patients with low expression levels(29% of decrease, AZD7762 n=18) of miR-134 had shorter overall survival, in comparison to patients with high expression levels(>29% of decrease, n=21) of miR-134 (Figure ?(Figure1C).1C). These results demonstrated that down-regulation of miR-134 was associated with poor prognosis. Collectively, decreased expression of miR-134 might be a critical factor in NSCLC progression and development. Open in a separate window Figure 1 MiR-134 is down-regulated in primary human lung cancer and NSCLC cell lines, and benefits for prognosisA. miR-134 is significantly decreased in primary human lung cancer tissues in comparison to adjacent-normal lung cancer tissues. n=39 for each group. B. The expression level of miR-134 in six NSCLC cell lines and normal HELF cells. Assays were performed in triplicate. C. Kaplan-Meier survival analysis revealed that down-regulated miR-134 is associated with poor prognosis in patients with non-small cell lung cancer. *< 0.001, Means SEM was shown. Statistical analysis was conducted using student t-test. Table 1 Correlation between miR-134 expression and clinicopathological parameters of NSCLC patients (n=39) < 0.05 Expression of cyclin D1 is up-regulated in primary human lung cancer and negatively expressed related to miR-134 cyclin D1 is important oncogene that shown strong power of oncogenicity, by promotion of cell growth, migration, invasion and epithelial AZD7762 mesenchymal transition (EMT), as well as inhibition of cell apoptosis in many tumors including lung cancer [39C41]. Thus, we next examined cyclin D1 expression in NSCLC and pair-matched adjacent lung tissues, and our western blot results demonstrated that cyclin D1 protein level was increased in lung cancer tissues in comparison to normal lung tissues (3.4-fold of increase) (Figure ?(Figure2A).2A). These results were confirmed by qRT-PCR of cyclin D1 mRNA expression (Figure ?(Figure2A).2A). Since cyclin D1 is the key role on regulation of cell cycle, aberrations of these three proteins might contribute to Rabbit Polyclonal to Galectin 3 human lung cancer. Moreover, we assessed the correlation between CCND1 mRNA and miR-134 expression in 39 lung cancer tissues, and results indicated expression of CCND1 mRNA and miR-134 showed a remarkably inverse correlation as calculated by Pearson correlation (r2=0.2021, =0.0041) (Figure ?(Figure2B2B). Open in a separate window Figure 2 Expression of is up-regulated in primary human lung cancer and negatively expressed related to miR-134A. Western-blot of cyclin D1 protein and qRT-PCR of CCND1 mRNA in lung cancer tissues and adjacent-normal lung cancers. n=39 for each group. B. Scatter plots showing the inverse association between miR-134 level and CCND1 mRNA.