Knockdown of lncRNA CCAT1 Inhibits the Progression of Colorectal Cancer via hsa-miR-4679 Mediating the Downregulation of GNG10.

Great concerns have raised crucial roles of long noncoding RNAs (lncRNAs) on colorectal cancer progression due to the increasing number of studies in cancer development. Previous studies reveal that lncRNA CCAT1 plays an important role in the progression of a variety of cancers. However, the role of lncRNA CCAT1 in colorectal cancer is still unclear. In this study, we found that in both colorectal tissues and cell lines the level of lncRNA CCAT1 was increased. Downregulation of lncRNA CCAT1 inhibited the proliferation, migration, and invasion of colorectal cell lines and promoted apoptosis. We then found that hsa-miR-4679 could bind to lncRNA CCAT1 directly, and with further functional analyses, we confirmed that lncRNA CCAT1 sponged hsa-miR-4679 to promote the progression of colorectal cancer. Next, we found that hsa-miR-4679 was directly bound to 3'UTR of GNG10 (guanine nucleotide-binding protein, gamma 10). GNG10 overexpression promoted the progression of colorectal cancer, and this phenotype could be reversed by miR-4679 mimics. At last, we knocked down CCAT1 in vivo and found that sh-CCAT1 reduced the tumor size and the number of proliferating cells. In summary, our findings revealed that lncRNA CCAT1 facilitated colorectal cancer progression via the hsa-miR-4679/GNG10 axis and provided new potential therapeutic targets for colorectal cancer.

RNA-Seq Analysis Identified XLOC_009190 as Potential Therapeutic Target for Lung Adenocarcinoma.

BACKGROUND: The abnormal regulation on the expression of lncRNAs had been linked to multiple kinds of cancers, including lung adenocarcinoma. METHODS: In this study, we carried out RNA-Seq on the three tumors and their paired normal samples from Chinese patients with lung adenocarcinoma. All the transcripts were de novo assembled, among which all the possible lncRNAs were predicted by tools including PLEK, CNCI, CPC, Blastp, hmmscan, and so forth. Their expression levels, altogether with the annotated mRNAs, were quantified. The weighted correlation network analysis and analysis of differential expression were carried out to explain the biological function of these novel lncRNAs. RESULTS: The weighted correlation network analysis showed that the lncRNAs, which were highly correlated with protein-coding genes, participated in various pathways, including PI3K kinase pathways. These lncRNAs were important regulators in biological processes. Next, the differentially expressed lncRNAs were identified, including four known lncRNAs and one novel lncRNA (XLOC_009190). The cis-regulation of this novel lncRNA might act on MGST1, which protected cells by conjugation and glutathione peroxidase functions. The trans-regulation of this lncRNA was investigated by its correlated mRNAs. The results showed that it possibly played a role in transmembrane receptors like G protein-coupled receptors and potassium channels. CONCLUSION: We proposed the potential biological function of XLOC_009190, but further experiments are needed to elucidate its roles and its potential to be the therapeutic target.

Identification of key genes and construction of microRNA-mRNA regulatory networks in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the most common type of lung tumor. Deregulation of microRNA may be involved in the occurrence of NSCLC and we aimed to find the potential prognostic biomarkers for NSCLC. The microRNA microarray expression profiles were downloaded from GEO dataset and then generated by applying robust multi-array average (RMA). The normalized data was analyzed with a Bioconductor package linear model for microarray data and an independent dataset was used to inspect the results. Then, the differentially expressed genes were identified using the limma package. Besides, in order to investigate the function of the differentially expressed microRNA in NSCLC, the GO and KEGG functional enrichment analysis were applied, and the GSEA analysis was performed for mining the therapeutic candidates. A total of 160 differentially expressed microRNAs were identified, among which 37 microRNAs showed significant expression changes (up-regulated and down-regulated) with the same method in the validation dataset GSE74190. Multiple cancer-related pathways, such as AMPK signaling pathway, AMPK signaling pathway, non-small cell lung cancer signaling pathway, were determined by performing the functional enrichment analysis. Besides, the results of GSEA analysis showed that the CCND1 was mostly enriched in lung cancer group. In conclusion, a set of differentially expressed microRNAs in NSCLC was identified and the CCND1 gene was determined as the potential prognostic biomarkers for NSCLC, providing useful information for discovery of future therapeutic targets and candidates in the clinical management of NSCLC.

Effect of serum choice on replicative senescence in mesenchymal stromal cells.

BACKGROUND AIMS: Multipotent mesenchymal stromal cells (MSCs) are promising candidates for innovative cell therapeutic applications. Before their use, however, they usually need to be expanded in vitro with serum-supplemented media. MSCs can undergo replicative senescence during in vitro expansion, but it is not yet clear how serum supplements influence this process. METHODS: In the present study, we compared how media supplemented with fetal bovine serum (FBS) or calf serum (CS) affected morphology, proliferation, differentiation, senescence and other functional characteristics of human umbilical cord-derived MSCs (UC-MSCs). RESULTS: UC-MSCs cultured in both FBS- and CS-containing media were able to differentiate along osteogenic and adipogenic lineages but ultimately reached proliferation arrest. However, senescence-associated characteristics, such as ß-galactosidase activity, reactive oxygen species levels, proliferation rate and gene expression, demonstrate that UC-MSCs grown with FBS have better proliferation potential and differentiation capacity. In contrast, UC-MSCs grown with CS have a higher proportion of apoptotic cells and senescent characteristics. Possible mechanisms for the observed phenotypes include changes in gene expression (Bax, p16, p21 and p53) and cytokine production (interleukin-6 and interleukin-8). CONCLUSIONS: This study demonstrates that FBS-supplemented media provides a better microenvironment for the expansion of UC-MSCs in vitro than CS-supplemented media. This work provides insight into MSCs generation practices for use in basic research and clinical therapies.

Host selection and niche differentiation in sucking lice (Insecta: Anoplura) among small mammals in southwestern China.

Understanding factors that shape host selection has been a classic issue in ecology, evolutionary biology, and epidemiological investigation. During the survey from 2000 to 2009, a total of 11,216 individuals of small mammals were captured from Yunnan Province in southwestern China. The captured small mammalian hosts belong to five orders, ten families, 35 genera, and 65 species and from their body surface, 38,885 individuals of ectoparasitic sucking lice were collected, which represent five families, seven genera, and 31 species. Based on niche overlap of dominant sucking lice on their primary hosts, we used hierarchical cluster analysis to sort different sucking louse species' resource utilizations of similar kind into respective categories. Given λ<5, there are only two groups clustered, however, sucking louse species' resource utilization was sorted into eight respective categories at λ=15. The results revealed that most species of sucking lice usually had high host specificity and a certain species of sucking louse usually restricted to one or few small mammalian species as their dominant hosts. Correspondence analysis was used to visualize associations between parasitic sucking lice and their small mammalian hosts, which suggested three different patterns of host resource utilization: species specialists, genera generalists, and multiple selections. For example, Sathrax durus (Johnson) only parasitized on species of Tupaia belangeri (Wagner), Hoplopleura edentula (Fahredholz) predominatly on genus of Eothenomys, and Polyplax reclinata (Nitzsch) on Family of Soricidae. Our results demonstrate that sucking lice have high host specificity and this might be due to coevolution between sucking lice and their hosts.