Tumor-suppressive miR-29c binds to MAPK1 inhibiting the ERK/MAPK pathway in pancreatic cancer.

INTRODUCTION: GEO- and TCGA-based data analysis suggested the differential expression of miR-29c in pancreatic cancer. However, limited data are available on the downstream mechanistic actions of miR-29c, which may fuel the in vitro and in vivo studies of pancreatic cancer. METHODS: The downstream target gene of miR-29c and the downstream ERK/MAPK pathway involved in pancreatic cancer were predicted by bioinformatics tools. Next, the expression of miR-29c and MAPK1 was determined in pancreatic cancer tissues and cells. After ectopic expression and depletion experiments in pancreatic cancer cells, oncogenic phenotypes of pancreatic cancer cells were tested by MTS assay, Transwell assay, and flow cytometry. Effects of miR-29c/MAPK1 on tumorigenic ability in vivo were evaluated in pancreatic cancer xenografts in nude mice. RESULTS: Through differential analysis, five pancreatic cancer-related miRNAs (hsa-miR-29c, hsa-miR-107, hsa-miR-324-3p, hsa-miR-375, and hsa-miR-210) were screened out, among which miR-29c was selected as the key miRNA related to prognosis of pancreatic cancer patients. miR-29c could target and inhibit MAPK1 to suppress the activation of ERK/MAPK pathway. miR-29c was downregulated in pancreatic cancer, and its high expression was related to the good prognosis of pancreatic cancer patients. Both in vitro and in vivo experiments demonstrated that restoration of miR-29c inhibited oncogenic phenotypes of pancreatic cancer cells, as well as repressed tumorigenic ability of pancreatic cancer cells in nude mice. CONCLUSIONS: Taken together, we unveil a novel miR-29c/MAPK1/ERK/MAPK axis that suppresses pancreatic cancer both in vitro and in vivo.

Per- and poly-fluoroalkyl substances in sediments from the water-level-fluctuation zone of the Three Gorges Reservoir, China: Contamination characteristics, source apportionment, and mass inventory and loadings.

Sixteen paired surface sediment samples (0-5 cm, n = 32) covering upstream to downstream of water-level-fluctuation zone of Three Gorges Reservoir, China were collected in March 2018 (following six months of submergence) and September 2018 (after six months of exposure). Seventeen per- and poly-fluoroalkyl substances (PFASs) were quantified to evaluate contamination characteristics, apportion source categories and estimate mass inventory and loadings. The concentration of ΣPFASs ranged from 0.26 to 0.82 ng·g-1 at high water-level (HWL) and 0.46-1.53 ng·g-1 at low water-level (LWL). Perfluorooctanoic acid (PFOA, mean: 0.32 ng·g-1) and perfluorooctane sulfonate (PFOS, mean: 0.12 ng·g-1) dominated, accounting 44.9% and 16.3% of the total PFASs, respectively. The distribution of PFASs was more influenced by anthropogenic activities than physicochemical parameters of the sediments. Positive matrix factorization (PMF) identified PFOA-based products was the major sources (40.1% and 38.6%, respectively). Besides, the direct sources of PFOA-, PFOS-, PFNA-and PFBA-based products played the predominant role, while the indirect degradation of precursors contributed relatively little. The sediment (0-5 cm) mass inventory of PFASs at LWL (57.5 kg) was higher than HWL (39.3 kg). The annual mass loadings of the total PFASs, PFOA, PFOS, perfluoroundecanoic acid (PFUdA) and perfluorononanoic acid (PFNA) from the upstream to the middle-lower reaches of Yangtze River were 27.4 kg, 11.1 kg, 4.63 kg, 2.89 kg and 2.57 kg, respectively. This study could provide the basic datasets of PFASs in surface sediments of the TGR, and also indicate an important transport of PFASs from upstream to the lower reaches, which should be further studied as well.