Exosomes are 30–120 nm endocytic membrane-derived vesicles that participate in cell-to-cell communication and protein and RNA delivery. Exosomes harbor a variety of proteins, nucleic acids, and lipids and are present in many and perhaps all bodily fluids. A significant body of literature has demonstrated that molecular constituents of exosomes, especially exosomal proteins and microRNAs (miRNAs), hold great promise as novel biomarkers for clinical diagnosis. In this minireview, we summarize recent advances in the research of exosomal biomarkers and their potential application in clinical diagnostics. We also provide a brief overview of the formation, function, and isolation of exosomes.

Abstract. Alternative splicing of precursor mRNA is an essential mechanism to increase the complexity of gene expression, and it plays an important role in cellular differentiation and organism development. Regulation of alternative splicing is a complicated process in which numerous interacting components are at work, including cis-acting elements and trans-acting factors, and is further guided by the functional coupling between transcription and splicing. Additional molecular features, such as chromatin structure, RNA structure and alternative transcription initiation or alternative transcription termination, collaborate with these basic components to generate the protein diversity due to alternative splicing.

No abstract

Chronic inflammation is one of the critical causes to promote the initiation and metastasis of solid malignancies including lung cancer (LC). Here, we aimed to investigate the prognostic roles of albumin (Alb)‐to‐fibrinogen (Fib) ratio (AFR), Fib and Alb in LC and to establish a novel effective nomogram combined with AFR. Four hundred twelve LC patients diagnosed between February 2005 and December 2014 were recruited in this prospective study. The prognostic roles of AFR, Fib, Alb, neutrophil‐to‐lymphocyte ratio (NLR), platelet‐to‐lymphocyte ratio (PLR) and monocyte‐to‐lymphocyte ratio (MLR) were identified by X‐tile software, Kaplan–Meier curve, Cox regression model, and time‐dependent ROC. Pretreatment high circulating Fib, low AFR, and Alb were significantly associated with increased risk of death for LC patients, especially for non‐small cell lung cancer (NSCLC) patients in all stages. The area under curves (AUCs) of AFR, Fib, and NLR were higher than them within Alb and PLR for predicting the survival of NSCLC patients. Moreover, we found that clinical outcome of high AFR patient with chemo‐radiotherapy was superior to low AFR patient; overall survival rate of stage II‐III NSCLC patients undergoing chemo‐radiotherapy was significantly lower than the surgical patients with treatment of adjuvant chemo‐radiotherapy(P = 0.001) in low AFR subgroup. On the contrary, clinical outcome of the patients receiving chemo‐radiotherapy was the same to the patients undergoing surgery and adjuvant chemo‐radiotherapy (P = 0.405) in high AFR subgroup. In addition, c‐index of predicted nomogram including AFR (0.717) for NSCLC patients with treatment of chemo‐radiotherapy was higher than that without AFR (0.707). Our findings demonstrated that circulating pretreatment AFR might be a potential biomarker to predict clinical efficacy of surgical resection and adjuvant chemo‐radiotherapy and be a prognostic biomarker for NSCLC individuals.

NOTCH signaling exerts essential roles in normal and malignant intestinal physiology and the homeostasis of cancer stem-like cells (CSC), but the basis for this latter role remains obscure. The signaling scaffold protein STRAP is upregulated in several cancers where it promotes tumorigenicity and metastasis. Here we report a novel oncogenic function for STRAP in maintaining CSC subpopulations in a heterogeneous mixture by antagonizing formation of the chromatin modifier PRC2 and by epigenetically activating NOTCH signals in human colorectal cancer (CRC). Silencing STRAP sensitized CRC cells to chemotherapeutic drugs in vitro and in vivo. STRAP depletion also contributed to a reduced stem-like phenotype of CRC cells, as indicated by reduced expression of the CSC signature and NOTCH signaling regulators in vitro and by diminished tumorigenesis in vivo. Genes encoding some upstream activators of NOTCH were highly enriched for H3K27me3, which form repressive chromatin domains upon STRAP silencing. Mechanistically, STRAP competitively disrupted association of the PRC2 subunits EZH2 and SUZ12, thereby inhibiting PRC2 assembly. Restoring the NOTCH pathway by lentiviral expression of NICD1 or HES1 in STRAP-depleted tumor cells reversed the CSC phenotype. In 90 CRC clinical specimens, a significant positive correlation was documented between the expression of STRAP and HES1. Overall, our findings illuminated a novel STRAP-NOTCH1-HES1 molecular axis as a CSC regulator in CRC, with potential implications to improve treatment of this disease.