Long noncoding RNA MGC27382 inhibits proliferation and metastasis of non-small cell lung cancer cells via down-regulating AKT/GSK3ß pathway.

PURPOSE: Persistent abnormal proliferation and long distant metastasis of tumors contribute to high mortality rate in non-small cell lung cancer (NSCLC) patients. Strategies that prevent NSCLC proliferation and/or metastasis have been studied but still need to be further explored. Numerous studies have proved the diversity functions of long noncoding RNAs (lncRNAs) exerted in cancer, including NSCLC. In this study, we aim to identify and investigate the role of novel lncRNAs in NSCLC progression. METHODS: RNA sequence data were retrieved from the Cancer Genome Atlas (TCGA), differentially expressed lncRNAs (DElncRNAs) were screened out based on the R language, then real-time PCR experiment was introduced to detect the DElncRNA expression levels. A series of experiments including MTT, cell cycle, transwell, and wound healing assays were employed to explore the effect of DElncRNA MGC27382 on cell proliferation and invasion ability. RESULTS: We detected that DElncRNA MGC27382 is down-regulated in NSCLC tissues and cells. Overexpression of MGC27382 prevented NSCLC cell proliferation via down-regulating cyclin D1 and cyclin E. Moreover, wound healing and transwell assays indicated that the ability of cell invasion and migration could be impaired when cells were treated with MGC27382 overexpression. Further studies demonstrated that MGC27382-mediated inhibition on NSCLC progression can be impaired by LY294002, which is a frequently used inhibitor of AKT/GSK3ß pathway. CONCLUSION: MGC27382 is down-regulated in NSCLC. It exerts an inhibitory role in NSCLC development through suppressing the AKT/GSK3ß pathway. Our results indicate that the lncRNA MGC27382 might be a tumor-suppressor gene in NSCLC. Overexpression of MGC27382 is thought to be a potential strategy for overcoming NSCLC progression.

DNA sequence polymorphism within the bovine adenosine monophosphate deaminase 1 (AMPD1) is associated with production traits in Chinese cattle.

The objectives of the present study were to detect an 18-bp deletion mutation in the bovine adenosine monophosphate deaminase 1 (AMPD1) gene and analyze its effect on growth traits in 2 Chinese cattle breeds using DNA sequencing and agarose electrophoresis. The five 19-bp polymerase chain reaction products of the AMPD1 gene exhibited 3 genotypes and 2 alleles: WW: homozygote genotype (wild-type); DD: homozygote genotype (mutant-type); WD: heterozygote genotype. Frequencies of the W allele varied from 66.15-70.35%. The associations between the 18-bp deletion mutation in the AMPD1 gene with production traits in 226 Jia-Xian red cattle was analyzed. The animals with genotype WW showed significantly higher heart girth and body weight than those with genotypes WD and DD at 24 months (P < 0.01). Our results indicate that the deletion mutation in the AMPD1 gene is associated with production traits, and may be used for marker-assisted selection in beef cattle breeding programs.

Combining Diffusion Tensor Imaging and Susceptibility Weighted Imaging on the Substantia Nigra of 1-Methyl-4-Phenyl-1, 2, 3, 6-Tetrahydropyridine (MPTP)-induced Rhesus Monkey Model of Parkinson's Disease.

Objective: The aim of this study was to evaluate whether combining diffusion tensor magnetic resonance imaging (DTI) and susceptibility weighted imaging (SWI) techniques would provide a sensitive method for differentiating between 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rhesus monkey model of Parkinson's disease (PD) and wild-type controls. Subjects and Methods: Seventeen rhesus monkeys were divided into two groups. A series of intramuscular injections of either saline (control group, n = 8) or MPTP (0.2 mg/kg body weight; PD group, n = 9) were given to the monkeys, twice a week. Then, SWI and DTI scans were obtained from the monkeys with Siemens Magnetom Verio 3.0T superconductive MRI system. Region of interest analysis was performed on substantia nigra pars compacta (SNc) and substantia nigra pars reticulata (SNr). In addition, immunohistochemical staining of tyrosine hydroxylase was applied to assess degeneration of SN dopaminergic neurons. Results: Monkeys in the PD group displayed mild to moderate motor symptoms assessed using Kurlan's scale. With SWI scans, decreased width of SNc but increased width of SNr was found in PD group monkeys compared to controls. Calculation of the ratios of widths of SNc and SNr to the anterior and posterior mesencephalic diameter also reflected narrower SNc but wider SNr than controls. Decreased SWI signal intensity of SNc and SNr suggested iron deposition in both subregions of SN. The DTI scans showed lower fractional anisotropy (FA) values in SNc of the PD group monkeys, while no change of FA values in SNr was detected. Immunohistochemical test displayed generalized loss of dopaminergic neurons in SN of PD group monkeys. Conclusion: Combining the use of DTI and SWI can provide a sensitive method for differentiating between MPTP-induced rhesus monkey model of PD and wild-type controls. This effective imaging modality might provide additional information for characteristic identification of PD at early stages, thus enhancing the ability to make early diagnosis, and monitor progression of the natural history and treatment effects.

Parallel proteomic analysis in muscle-invasive bladder transitional cell carcinoma and cancer-related stroma.

To bring about improvements in cancer biology research and elucidate mechanism-based therapeutic targets, we studied the proteome expression profile of purified normal urothelial cells (cancer cells) and normal stromal cells (cancerous stromal cells). Based on the expression profile, biomarker discovery and the mechanisms of multi-step carcinogenesis were explored. We found that 1412/1403 unique proteins commonly appeared in 4 sets of paired cancer/normal tissue, and 1753 proteins were differentially expressed. Three hundred and forty-one proteins were repeatedly expressed in both cancer and cancer stromal cells; 358 proteins were repeatedly expressed in both normal urothelial and normal stromal cells. Among them, 186/203 proteins were specific repeat expressions in cancer/normal tissue and thought to play an important role in cancer-stroma interactions. Differential proteins were further analyzed using bioinformatic tools and compared with the published literature. GO enrichment/depletion analysis indicated that carcinogenesis involved all the biological processes and all the cellular components. Five hundred and sixty-eight differential proteins were located in the well-known biological Kyoto Encyclopedia of Genes and Genomes pathways, including metabolic pathways, ribosome spliceosome, and endocytosis. One hundred and thirty-nine of the 186 proteins that displayed specific repeat expressions in cancer tissue were located in the biological Kyoto Encyclopedia of Genes and Genomes pathways and are thought to be candidate biomarkers for targeted therapy.