No abstract

MicroRNAs (miRNAs) are small non-coding RNAs that function by base pairing with messenger RNAs, thereby regulating protein expression. Functional studies indicate that miRNAs are involved in the regulation of almost every biological pathway. Moreover, changes in miRNA expression are associated with several human pathologies, including cancer. Dysregulation and aberrant expression of microRNA-100 (miR-100) have been reported to be involved in tumorigenesis and tumor progression of several cancer types, suggesting that miR-100 might serve as a diagnostic and/or prognostic marker for human malignancy. In this review, we summarize the potential application of miR-100 in cancer treatment and as a new molecular marker for cancer prognosis and diagnosis. We will provide a brief introduction to miR-100 and discuss its role as a non-invasive biomarker and a potential therapeutic target in human cancers.

Background Myofibroblast differentiation and extracellular matrix (ECM) deposition are observed in chronic obstructive pulmonary disease (COPD). However, the mechanisms of regulation of myofibroblast differentiation remain unclear. Materials and methods We detected let‐7 levels in peripheral lung tissues, serum and primary bronchial epithelial cells of COPD patients and cigarette smoke (CS)‐exposed mice. IL‐6 mRNA was explored in lung tissues of COPD patients and CS‐exposed mice. IL‐6 protein was detected in cell supernatant from primary epithelial cells by ELISA. We confirmed the regulatory effect of let‐7 on IL‐6 by luciferase reporter assay. Western blotting assay was used to determine the expression of α‐SMA, E‐cadherin and collagen I. In vitro, cell study was performed to demonstrate the role of let‐7 in myofibroblast differentiation and ECM deposition. Results Low expression of let‐7 was observed in COPD patients, CS‐exposed mice and CS extract (CSE)‐treated human bronchial epithelial (HBE) cells. Increased IL‐6 was found in COPD patients, CS‐exposed mice and CSE‐treated HBE cells. Let‐7 targets and silences IL‐6 protein coding genes through binding to 3’ untranslated region (UTR) of IL‐6. Normal or CSE‐treated HBE cells were co‐cultured with human embryonic lung fibroblasts (MRC‐5 cells). Reduction of let‐7 in HBE cells caused myofibroblast differentiation and ECM deposition, while increase of let‐7 mimics decreased myofibroblast differentiation phenotype and ECM deposition. Conclusion We demonstrate that CS reduced let‐7 expression in COPD and, further, identify let‐7 as a regulator of myofibroblast differentiation through the regulation of IL‐6, which has potential value for diagnosis and treatment of COPD.

Background. cIAP2 is involved in necroptosis as a key upstream regulation factor. We aimed to investigate the role of cIAP2 in ARDS/ALI induced by H7N9 virus through regulating the RIPK1/3 necroptosis pathway. Methods. Lung tissues of 11 patients who died from ARDS-complicated H7N9 infection between 2013 and 2016 were obtained as the H7N9-ARDS group. Lung tissues near benign lung nodules were acquired as the control group. Histological changes were evaluated by H&E staining. Protein levels of cIAP2, RIPK1, RIPK3, p-RIPK3, MLKL, and p-MLKL in the lung tissues were detected by Western Blot. The mRNA levels of cIAP2, RIPK1, and RIPK3 were detected by real-time PCR. Results. H7N9 virus infection had a high mortality, with ARDS being the leading cause of death. The protein level of cIAP2 in the experimental group was lower than that in the control group (P<0.05). However, the experimental group showed higher RIPK1, RIPK3, and p-RIPK3 protein levels than the control group (P<0.05), as well as the expression level of MLKL and p-MLKL protein, which is a key downstream protein in necroptosis (P<0.05). Conclusion. In tissues from patients with fatal H7N9, downregulation of cIAP2 and induction of necroptosis was observed. We could speculate that necroptosis of the pulmonary epithelium is associated with severe H7N9 infection leading to ARDS. Thus, necroptosis inhibition may be a novel therapy for H7N9 influenza virus.