MiR-195 suppresses tumor growth and is associated with better survival outcomes in several malignancies including non-small cell lung cancer (NSCLC). Our previous study showed high miR-195 plasma levels associated with favorable overall survival of non-smoking women with lung adenocarcinoma. To further elucidate role of miR-195 in NSCLC, we conducted in vitro experiment as well as clinical studies in a cohort of 299 NSCLC samples. We demonstrated that miR-195 expression was lower in tumor tissues and was associated with poor survival outcome. Overexpression of miR-195 suppressed tumor cell growth, migration and invasion. We discovered that CHEK1 was a direct target of miR-195, which decreased CHEK1 expression in lung cancer cells. High expression of CHEK1 in lung tumors was associated with poor overall survival. Our results suggest that miR-195 suppresses NSCLC and predicts lung cancer prognosis.

There is strong evidence to support a considerable alteration of the gut microbiome after bariatric surgery. Deeper investigations are required to confirm the mechanisms that link the gut microbiome and metabolic alterations in human metabolism.

Purpose: Our aim was to investigate whether microRNAs can predict the clinical outcome of patients with gastric cancer. We used integrated analysis of microRNA and mRNA expression profiles to identify gastric cancer microRNA subtypes and their underlying regulatory scenarios.Experimental Design: MicroRNA-based gastric cancer subtypes were identified by consensus clustering analysis of microRNA profiles of 90 gastric cancer tissues. Activated pathways in the subtypes were identified by gene expression profiles. Further integrated analysis was conducted to model a microRNA regulatory network for each subtype. RNA and protein expression were analyzed by RT-PCR and tissue microarray, respectively, in a cohort of 385 gastric cancer cases (including the 90 cases for profiling) to validate the key microRNAs and targets in the network. Both in vitro and in vivo experiments were carried out to further validate the findings.Results: MicroRNA profiles of 90 gastric cancer cases identified two microRNA subtypes significantly associated with survival. The poor-prognosis gastric cancer microRNA subtype was characterized by overexpression of epithelial-to-mesenchymal transition (EMT) markers. This gastric cancer "mesenchymal subtype" was further validated in a patient cohort comprising 385 cases. Integrated analysis identified a key microRNA regulatory network likely driving the gastric cancer mesenchymal subtype. Three of the microRNAs (miR-200c, miR-200b, and miR-125b) targeting the most genes in the network were significantly associated with survival. Functional experiments demonstrated that miR-200b suppressed ZEB1, augmented E-cadherin, inhibited cell migration, and suppressed tumor growth in a mouse model. Conclusions:We have uncovered a key microRNA regulatory network that defines the mesenchymal gastric cancer subtype significantly associated with poor overall survival in gastric cancer. Clin Cancer Res; 20(4); 878-89. Ó2013 AACR.