Evidence suggests that fasting exerts extensive antitumor effects in various cancers, including colorectal cancer (CRC). However, the mechanism behind this response is unclear. We investigate the effect of fasting on glucose metabolism and malignancy in CRC. We find that fasting upregulates the expression of a cholesterogenic gene, Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1), during the inhibition of CRC cell aerobic glycolysis and proliferation. In addition, the downregulation of FDFT1 is correlated with malignant progression and poor prognosis in CRC. Moreover, FDFT1 acts as a critical tumor suppressor in CRC. Mechanistically, FDFT1 performs its tumor-inhibitory function by negatively regulating AKT/mTOR/HIF1α signaling. Furthermore, mTOR inhibitor can synergize with fasting in inhibiting the proliferation of CRC. These results indicate that FDFT1 is a key downstream target of the fasting response and may be involved in CRC cell glucose metabolism. Our results suggest therapeutic implications in CRC and potential crosstalk between a cholesterogenic gene and glycolysis.

Neuroblastoma (NB) is the most common type of extracranial solid tumor found in children. Despite several treatment options, patients with advanced stage disease have a poor prognosis. Previous studies have reported that enhancer of zeste homolog 2 (EZH2) and long non-coding RNAs (lncRNAs) have abnormal expression levels in NB and participate in tumorigenesis and NB development. However, the association between EZH2 and lncRNAs remain unclear. In the present study, RNA immunoprecipitation-sequencing (RIP-seq) was used to analyze the lncRNAs binding to EZH2. Following EZH2 knockdown via short hairpin RNA, RNA-seq was performed in shEZH2 and control groups in SH-SY5Y cells. Chromatin IP (ChIP)-seq was used to determine the genes that may be regulated by EZH2. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to identify the signaling pathways involved in NB. The results from RIP-seq identified 94 lncRNAs, including SNHG7, SNHG22, KTN-AS1 and Linc00843. Furthermore, results from RNA-seq demonstrated that, following EZH2 knockdown, 448 genes were up- and 571 genes were downregulated, with 32 lncRNAs up- and 35 downregulated and differentially expressed compared with control groups. Certain lncRNAs, including MALAT1, H19, Linc01021 and SNHG5, were differentially expressed in EZH2-knockdown group compared with the control group. ChIP-seq identified EZH2 located in the promoter region of 138 lncRNAs including CASC16, CASC15, LINC00694 and TBX5-AS1. In summary, the present study demonstrated that certain lncRNAs directly bound EZH2 and regulated EZH2 expression levels. A number of these lncRNAs that are associated with EZH2 may participate in NB tumorigenesis.

Fabricating Ti alloy based dental implants with defined porous scaffold structure is a promising strategy for improving the osteoinduction of implants. In this study, we use Laser Beam Melting (LBM) 3D printing technique to fabricate porous Ti6Al4V dental implant prototypes with three controlled pore sizes (200, 350 and 500 μm). The mechanical stress distribution in the surrounding bone tissue is characterized by photoelastography and associated finite element simulation. Forin-vitrostudies, experiments on implants’ biocompatibility and osteogenic capability are conducted to evaluate the cellular response correlated to the porous structure. As the preliminary results, porous structured implants show a lower stress-shielding to the surrounding bone at the implant neck and a more densed distribution at the bottom site compared to the reference implant. From the cell proliferation tests and the immunofluorescence images, 350 and 500 μm pore sized implants demonstrate a better biocompatibility in terms of cell growth, migration and adhesion. Osteogenic genes expression of the 350 μm group is significantly increased alone with the ALP activity test. All these suggest that a pore size of 350 μm provides an optimal provides an optimal potential for improving the mechanical shielding to the surrounding bones and osteoinduction of the implant itself.

Sepsis is a systemic inflammation caused by infection. The balance between M1–M2 macrophage polarization has an essential role in the pathogenesis of sepsis. However, the exact mechanism underlying macrophage polarization is unclear. We previously showed that levels of malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) were significantly elevated in septic patients compared with those in nonseptic patients, and involved in the activation of Toll-like receptor (TLR) 2/c-Jun N-terminal kinase (JNK)/nuclear factor (NF)-κB pathway. In the present study, we explored whether MFHAS1 was involved in macrophage polarization and determined the effect of MFHAS1 on inflammation. We performed in vitro pulldown assays and in vivo co-immunoprecipitation assays and found that E3 ubiquitin ligase praja2 could directly bind to MFHAS1. In situ immunostaining analysis confirmed the colocalization of endogenous praja2 with MFHAS1. We first reported that praja2 promotes the accumulation of ubiquitylated MFHAS1 but does not degrade it. Moreover, our results indicate that MFHAS1 ubiquitylation by praja2 positively regulates TLR2-mediated JNK/p38 pathway and promotes M1 macrophage polarization, M2 to M1 macrophage transformation and inflammation.

Modification of m6A, as the most abundant mRNA modification, plays diverse roles in various biological processes in eukaryotes. Emerging evidence has revealed that m6A modification is closely associated with the activation and inhibition of tumor pathways, and it is significantly linked to the prognosis of cancer patients. Aberrant reduction or elevated expression of m6A regulators and of m6A itself have been identified in numerous tumors. In this review, we give a description of the dynamic properties of m6A modification regulators, such as methyltransferases, demethylases, and m6A binding proteins, and indicate the value of the balance between these proteins in regulating the expression of diverse genes and the underlying effects on cancer development. Furthermore, we summarize the “dual-edged weapon” role of RNA methylation in tumor progression and discuss that RNA methylation can not only result in tumorigenesis but also lead to suppression of tumor formation. In addition, we summarize the latest research progress on small-molecule targeting of m6A regulators to inhibit or activate m6A. These studies indicate that restoring the balance of m6A modification via targeting specific imbalanced regulators may be a novel anti-cancer strategy.