Promotion of tumor progression by exosome transmission of circular RNA circSKA3.

We performed in vitro and in vivo experiments to investigate the role of the circular RNA circSKA3 in tumor development. We examined the effects of circSKA3 on mediating breast cancer metastasis. In vitro, we found that the circular RNA circSKA3 was transferred between breast cancer cells, which were decreased by inhibiting exosome secretion. In vivo, circSKA3-containing exosomes potentiated tumor development and invasion that were inhibited by blocking exosome transmission. The ascites isolated from tumor-bearing mice or breast cancer patients showed high levels of circSKA3 and integrin ß1. Single-cell culture and single-cell PCR showed that circSKA3 was heterogeneously expressed, the cells expressing higher levels of circSKA3 had a higher potential to form large colonies. This property was similar to c-myc, but circSKA3 expression had no correlation with c-myc levels. The effects of circSKA3 on cell migration and invasion appeared to predominate c-myc functions. By releasing circSKA3-containing exosomes to cancer cells expressing lower levels of circSKA3, the large colonies could regulate the activities of small colonies, enhancing the tumor-forming capacity of the entire population. Thus, we provide evidence that the transmission of circular RNAs in tumor-derived exosomes may allow for the maintenance of advantageous invasive sub-clones in breast cancer.

Clinical and Microbiological Investigation of the Effects of Probiotics Combined with Scaling and Root Planing in the Management of Chronic Periodontitis: A Randomized, Controlled Study.

AIM: To assess the adjunctive effect of probiotics to scaling and root planing in the management of chronic periodontitis. MATERIALS AND METHODS: Thirty systemically healthy subjects in the age range of 20 - 55 years suffering from chronic generalized periodontitis were selected and randomly assigned to a control group of patients who received scaling and root planing (SRP) alone, or a test group of patients who received SRP supplemented with probiotic administration, i.e., Bifilac lozenges. The following baseline clinical parameters were recorded at selected teeth: plaque index, gingival index, probing pocket depth and relative attachment level. Microbiological counts of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Prevotella intermedia were assessed in pooled subgingival plaque samples. The parameters were recorded again at 30 days, 45 days and 3 months from baseline. RESULTS: Statistically significant reductions were observed for plaque index, gingival index, and probing pocket depth, and a significant gain in relative attachment level in both groups. Microbiological analysis showed significant reduction for P. gingivalis at all recall intervals in the test group compared to controls. The intergroup comparison for differences in mean counts of P. gingivalis was found to be significant for the test group at 3 months (p = 0.028). CONCLUSION: Probiotics can be considered as a potentially safe and effective adjunct to scaling and root planing in the management of chronic periodontitis.

Noncoding RNAs in Tumor Angiogenesis.

Solid tumors require angiogenesis to grow beyond 2 mm in size. In most cases, tumor cells undergo angiogenic switch and secrete substances that are required for generation of new capillary sprouting from existing blood vessels. Tumor angiogenesis is driven by a complex interplay between pro-angiogenic (VEGF/VEGFR, PDGF/PDGFR) and anti-angiogenic factors (TSP-1/TSP-2) within the tumor microenvironment. In addition, control of tissue remodeling and degradation by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) contribute to tumor angiogenesis. Furthermore, tumor suppressors or oncogenes that control cellular motility and maintain or promote hypoxia (HIFs and MYC) are also actively playing roles in tumor angiogenesis. Noncoding RNAs (ncRNAs), including microRNAs, are a novel class of regulatory molecules that control the gene expression in a posttranscriptional manner. MicroRNAs regulate important physiological processes, such as proliferation, apoptosis, and differentiation, as well as pathological conditions including oncogenesis. Accumulating evidence suggests that microRNAs directly modulate the process of angiogenesis by targeting important angiogenic factors and signaling molecules. Understanding the molecular mechanism behind the regulation of angiogenesis by microRNAs is important due to their therapeutic potential which may lead to improving outcome for cancer patients. Besides, ncRNAs with a regulatory role in angiogenesis, such as long noncoding RNAs (lncRNAs), have been identified in the genome. However, the mechanisms of the vast majority of lncRNAs are currently unknown. For the few lncRNAs characterized at the functional level, accumulating evidence shows that they play important roles in malignant diseases. The function and mechanism in angiogenesis will be described in this chapter.

Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2.

Most RNAs generated by the human genome have no protein-coding ability and are termed non-coding RNAs. Among these include circular RNAs, which include exonic circular RNAs (circRNA), mainly found in the cytoplasm, and intronic RNAs (ciRNA), predominantly detected in the nucleus. The biological functions of circular RNAs remain largely unknown, although ciRNAs have been reported to promote gene transcription, while circRNAs may function as microRNA sponges. We demonstrate that the circular RNA circ-Foxo3 was highly expressed in non-cancer cells and were associated with cell cycle progression. Silencing endogenous circ-Foxo3 promoted cell proliferation. Ectopic expression of circ-Foxo3 repressed cell cycle progression by binding to the cell cycle proteins cyclin-dependent kinase 2 (also known as cell division protein kinase 2 or CDK2) and cyclin-dependent kinase inhibitor 1 (or p21), resulting in the formation of a ternary complex. Normally, CDK2 interacts with cyclin A and cyclin E to facilitate cell cycle entry, while p21works to inhibit these interactions and arrest cell cycle progression. The formation of this circ-Foxo3-p21-CDK2 ternary complex arrested the function of CDK2 and blocked cell cycle progression.

Purification and identification of a polysaccharide from medicinal mushroom Amauroderma rude with immunomodulatory activity and inhibitory effect on tumor growth.

Medicinal mushrooms in recent years have been the subject of many experiments searching for anticancer properties. We previously screened thirteen mushrooms for their potential in inhibiting tumor growth, and found that the water extract of Amauroderma rude exerted the highest activity. Previous studies have shown that the polysaccharides contained in the water extract were responsible for the anticancer properties. This study was designed to explore the potential effects of the polysaccharides on immune regulation and tumor growth. Using the crude Amauroderma rude extract, in vitro experiments showed that the capacities of spleen lymphocytes, macrophages, and natural killer cells were all increased. In vivo experiments showed that the extract increased macrophage metabolism, lymphocyte proliferation, and antibody production. In addition, the partially purified product stimulated the secretion of cytokines in vitro, and in vivo. Overall, the extract decreased tumor growth rates. Lastly, the active compound was purified and identified as polysaccharide F212. Most importantly, the purified polysaccharide had the highest activity in increasing lymphocyte proliferation. In summary, this molecule may serve as a lead compound for drug development.