There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

The transdifferentiation of epithelial cells into motile mesenchymal cells, a process known as epithelial-mesenchymal transition (EMT), is integral in development, wound healing and stem cell behaviour, and contributes pathologically to fibrosis and cancer progression. This switch in cell differentiation and behaviour is mediated by key transcription factors, including SNAIL, zinc-finger E-box-binding (ZEB) and basic helix-loop-helix transcription factors, the functions of which are finely regulated at the transcriptional, translational and post-translational levels. The reprogramming of gene expression during EMT, as well as non-transcriptional changes, are initiated and controlled by signalling pathways that respond to extracellular cues. Among these, transforming growth factor-β (TGFβ) family signalling has a predominant role; however, the convergence of signalling pathways is essential for EMT.

Molecular mechanisms of epithelial–mesenchymal transition

CA : A Cancer Journal for Clinicians

Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

/pdf/discovery-and-refinement-of-loci-associated-with-lipid-17wc78w8iu.pdf

Discovery and refinement of loci associated with lipid levels

Cetuximab Monotherapy and Cetuximab plus Irinotecan in Irinotecan-Refractory Metastatic Colorectal Cancer

Background
MicroRNAs (miRNAs) are involved in cancer development and progression, acting as tumor suppressors or oncogenes. Our previous studies have revealed that miR-148a and miR-152 are significantly down-regulated in gastrointestinal cancers. Interestingly, miR-148b has the same "seed sequences" as miR-148a and miR-152. Although aberrant expression of miR-148b has been observed in several types of cancer, its pathophysiologic role and relevance to tumorigenesis are still largely unknown. The purpose of this study was to elucidate the molecular mechanisms by which miR-148b acts as a tumor suppressor in gastric cancer.

/pdf/microrna-148b-is-frequently-down-regulated-in-gastric-cancer-3ov31r6ifr.pdf

MicroRNA-148b is frequently down-regulated in gastric cancer and acts as a tumor suppressor by inhibiting cell proliferation

Thousands of genes have been well demonstrated to play important roles in cancer progression. As genes do not function in isolation, they can be grouped into “networks” based on their interactions. In this study, we discover a network regulating Claudin-4 in gastric cancer. We observe that Claudin-4 is up-regulated in gastric cancer and is associated with poor prognosis. Claudin-4 reinforce proliferation, invasion, and EMT in AGS, HGC-27, and SGC-7901 cells, which could be reversed by miR-596 and miR-3620-3p. In addition, lncRNA-KRTAP5-AS1 and lncRNA-TUBB2A could act as competing endogenous RNAs to affect the function of Claudin-4. Our results suggest that non-coding RNAs play important roles in the regulatory network of Claudin-4. As such, non-coding RNAs should be considered as potential biomarkers and therapeutic targets against gastric cancer. Non-coding RNAs can modify the expression of proteins in cancer networks. Here the authors reveal a regulatory network in gastric cancer whereby claudin-4 expression is reduced by specific miRNAs, which are in turn bound by specific lncRNAs acting as competing endogenous RNAs (ceRNAs), resulting in increased claudin-4 expression.

/pdf/non-coding-rnas-participate-in-the-regulatory-network-of-1kileojv2n.pdf

Non-coding RNAs participate in the regulatory network of CLDN4 via ceRNA mediated miRNA evasion

Altered Expression of MiR-148a and MiR-152 in Gastrointestinal Cancers and Its Clinical Significance

MicroRNAs(miRNA) are noncoding RNAs of about 19–23 nucleotides that are crucial for many biological processes. Members of the microRNA-148/152(miR-148/152) family, which include microRNA-148a(miR-148a), microRNA-148b(miR-148b), and microRNA-152(miR-152), are expressed differently in tumor and nontumor tissues and are involved in the genesis and development of disease. Furthermore, members of the miR-148/152 family are important in the growth and development of normal tissues. Members of the miR-148/152 family regulate target genes and are regulated by methylation of CPG islands. In this review, we report recent studies on the expression of members of the miR-148/152 family, methylation of CPG islands, and their target genes in different diseases, as well as in normal tissues.

/pdf/the-microrna-148-152-family-multi-faceted-players-h000lo4tn0.pdf

The MicroRNA-148/152 Family: Multi-faceted Players

Background The clinical value of the prognostic nutritional index (PNI) in gastric cancer (GC) remains controversial. Therefore, we performed the meta-analysis to determine the prognostic and clinicopathological values of PNI in patients with GC. Methods A literature search was performed in the PubMed, Embase, and Web of Science databases. Hazard ratios (HRs) and odds ratios (ORs) were extracted to estimate the association of PNI with survival and clinicopathological characteristics, respectively. Results Ten studies involving 3396 patients with GC were analyzed. The pooled results indicated that a low PNI was a significant predictor of poor overall survival (OS) (HR = 1.89, 95% confidence interval [CI] = 1.67–2.13, P  Conclusion PNI was a predictive indicator of survival and postoperative complications, and was associated with clinicopathological features in GC patients. However, a low PNI was not significantly associated with poor OS in patients with GC at stage IV.

Yongxi Song

Papers

MicroRNA-148b is frequently down-regulated in gastric cancer and acts as a tumor suppressor by inhibiting cell proliferation

Non-coding RNAs participate in the regulatory network of CLDN4 via ceRNA mediated miRNA evasion

Altered Expression of MiR-148a and MiR-152 in Gastrointestinal Cancers and Its Clinical Significance

The MicroRNA-148/152 Family: Multi-faceted Players

The prognostic nutritional index is a predictive indicator of prognosis and postoperative complications in gastric cancer: A meta-analysis