CREB1 contributes colorectal cancer cell plasticity by regulating lncRNA CCAT1 and NF-κB pathways.

The CREB1 gene encodes an exceptionally pleiotropic transcription factor that frequently dysregulated in human cancers. CREB1 can regulate tumor cell status of proliferation and/or migration; however, the molecular basis for this switch involvement in cell plasticity has not fully been understood yet. Here, we first show that knocking out CREB1 triggers a remarkable effect of epithelial-mesenchymal transition (EMT) and leads to the occurrence of inhibited proliferation and enhanced motility in HCT116 colorectal cancer cells. By monitoring 45 cellular signaling pathway activities, we find that multiple growth-related pathways decline significantly while inflammatory pathways including NF-κB are largely upregulated in comparing between the CREB1 wild-type and knocked out cells. Mechanistically, cells with CREB1 knocked out show downregulation of MYC as a result of impaired CREB1-dependent transcription of the oncogenic lncRNA CCAT1. Interestingly, the unbalanced competition between the coactivator CBP/p300 for CREB1 and p65 leads to the activation of the NF-κB pathway in cells with CREB1 disrupted, which induces an obvious EMT phenotype of the cancer cells. Taken together, these studies identify previously unknown mechanisms of CREB1 in CRC cell plasticity via regulating lncRNA CCAT1 and NF-κB pathways, providing a critical insight into a combined strategy for CREB1-targeted tumor therapies.

Wnt/ß-catenin pathway transactivates microRNA-150 that promotes EMT of colorectal cancer cells by suppressing CREB signaling.

A hallmark of aberrant activation of the Wnt/ß-catenin signaling pathway has been observed in most colorectal cancers (CRC), but little is known about the role of non-coding RNAs regulated by this pathway. Here, we found that miR-150 was the most significantly upregulated microRNA responsive to elevated of Wnt/ß-catenin signaling activity in both HCT116 and HEK293T cells. Mechanistically, the ß-catenin/LEF1 complex binds to the conserved TCF/LEF1-binding element in the miR-150 promoter and thereby transactivates its expression. Enforced expression of miR-150 in HCT116 cell line transformed cells into a spindle shape with higher migration and invasion activity. miR-150 markedly suppressed the CREB signaling pathway by targeting its core transcription factors CREB1 and EP300. Knockdown of CREB1 or EP300 and knockout of CREB1 by CRISPR/Cas9 phenocopied the epithelial-mesenchymal transition (EMT) observed in HCT116 cells in response to miR-150 overexpression. In summary, our data indicate that miR-150 is a novel Wnt effector that may significantly enhance EMT of CRC cells by targeting the CREB signaling pathway.

Novel resource utilization of refloated algal sludge to improve the quality of organic fertilizer.

Without further management, large amounts of refloated algal sludge from Taihu Lake to retrieve nitrogen and phosphorus resources may result in serious secondary environmental pollution. The possibility of utilization of algal sludge to improve the quality of organic fertilizer was investigated in this study. Variations of physicochemical properties, germination index (GI) and microcystin (MC) content were analysed during the composting process. The results showed that the addition of algal sludge improved the contents of nutrients, common free amino acids and total common amino acids in the novel organic fertilizer. Rapid degradation rates of MC-LR and MC-RR, a high GI value and more abundance of culturable protease-producing bacteria were observed during the composting process added with algal sludge. Growth experiments showed that the novel organic fertilizer efficiently promoted plant growth. This study provides a novel resource recovery method to reclaim the Taihu Lake algal sludge and highlights a novel method to produce a high-quality organic fertilizer.