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The regulatory loop between long noncoding RNAs (lncRNAs) and microRNAs has a dynamic role in transcriptional and translational regulation, and is involved in cancer. However, the regulatory circuitry between lncRNAs and microRNAs in tumorigenesis remains elusive. Here we demonstrate that a nuclear lncRNA LINC00336 is upregulated in lung cancer and functions as an oncogene by acting as a competing endogenous RNA (ceRNAs). LINC00336 bound RNA-binding protein ELAVL1 (ELAV-like RNA-binding protein 1) using nucleotides 1901–2107 of LINC00336 and the RRM interaction domain and key amino acids (aa) of ELAVL1 (aa 101–213), inhibiting ferroptosis. Moreover, ELAVL1 increased LINC00336 expression by stabilizing its posttranscriptional level, whereas LSH (lymphoid-specific helicase) increased ELAVL1 expression through the p53 signaling pathway, further supporting the hypothesis that LSH promotes LINC00336 expression. Interestingly, LINC00336 served as an endogenous sponge of microRNA 6852 (MIR6852) to regulate the expression of cystathionine-β-synthase (CBS), a surrogate marker of ferroptosis. Finally, we found that MIR6852 inhibited cell growth by promoting ferroptosis. These data show that the network of lncRNA and ceRNA has an important role in tumorigenesis and ferroptosis.

Cancer cells frequently display fundamentally altered cellular metabolism, which provides the biochemical foundation and directly contributes to tumorigenicity and malignancy. Rewiring of metabolic programmes, such as aerobic glycolysis and increased glutamine metabolism, are crucial for cancer cells to shed from a primary tumor, overcome the nutrient and energy deficit, and eventually survive and form metastases. However, the role of lipid metabolism that confers the aggressive properties of malignant cancers remains obscure. The present review is focused on key enzymes in lipid metabolism associated with metastatic disease pathogenesis. We also address the function of an important membrane structure-lipid raft in mediating tumor aggressive progression. We enumerate and integrate these recent findings into our current understanding of lipid metabolic reprogramming in cancer metastasis accompanied by new and exciting therapeutic implications.

Mitochondria are the major cellular energy‐producing organelles and intracellular source of reactive oxygen species. These organelles are responsible for driving cell life and death through mitochondrial network structure homeostasis, which is determined by a balance of fission and fusion. Recent advances revealed that a number of components of the fission and fusion machinery, including dynamin‐related protein 1 (Drp1), mitofusin1/2 (Mfn1/2) and Optic atrophy 1 (OPA1), that have been implicated in mitochondrial shape changes are indispensible for autophagy, apoptosis and necroptosis. Drp1 is the main regulator of mitochondrial fission and has become a key point of contention. The controversy focuses on whether Drp1 is directly involved in the regulation of cell death and, if involved, whether is it a stimulator or a negative regulator of cell death. Here, we examine the relevance of the homeostasis of the mitochondrial network structure in 3 different types of cell death, including autophagy, apoptosis and necroptosis. Furthermore, a variety of cancers often exhibit a fragmented mitochondrial phenotype. Thus, the fragmented ratio can reflect tumor progression that predicts prognosis and therapeutic response. In addition, we investigate whether the targeting of the mitochondrial fission protein Drp1 could be a novel therapeutic approach. Here, we examine the relevance of the homeostasis of the mitochondrial network structure in 3 different types of cell death, including autophagy, apoptosis and necroptosis. Furthermore, a variety of cancers often exhibit a fragmented mitochondrial phenotype. Targeting the mitochondrial fission protein Drp1or other shaping proteins is becoming a topic of interest. Further studies are needed to understand the differential effects of oncogenic signaling pathways on mitochondrial dynamics and to identify additional new signaling axes that regulate mitochondrial network structure homeostasis.

Epstein–Barr virus is an important cancer causing virus. Nasopharyngeal carcinoma is an infection-related cancer strongly driven by Epstein–Barr virus. In this cancer model, we identified the major host targets of latent membrane protein 1 which is a driving oncogene encoded by Epstein–Barr virus in latency infection. latent membrane protein 1 activates several oncogenic signaling axes causing multiple malignant phenotypes and therapeutic resistance. Also, Epstein–Barr virus up-regulates DNA methyltransferase 1 and mediates onco-epigenetic effects in the carcinogenesis. The collaborating pathways activated by latent membrane protein 1 constructs an oncogenic signaling network, which makes latent membrane protein 1 an important potential target for effective treatment or preventive intervention. In Epstein–Barr virus lytic phase, the plasma level of Epstein–Barr virus DNA is considered as a distinguishing marker for nasopharyngeal carcinoma in subjects from healthy high-risk populations and is also a novel prognostic marker in Epstein–Barr virus-positive nasopharyngeal carcinoma. Now the early detection and screening of the lytic proteins and Epstein–Barr virus DNA have been applied to clinical and high-risk population. The knowledge generated regarding Epstein–Barr virus can be used in Epstein–Barr virus based precision cancer prevention and therapy in the near future.

Sepsis and sepsis‐induced skeletal muscle atrophy are common in patients in intensive care units with high mortality, while the mechanisms are controversial and complicated. In the present study, the atrophy of skeletal muscle was evaluated in sepsis mouse model as well as the apoptosis of muscle fibres. Sepsis induced atrophy of skeletal muscle and apoptosis of myofibres in vivo and in vitro. In cell‐based in vitro experiments, lipopolysaccharide (LPS) stimulation also inhibited the proliferation of myoblasts. At the molecular level, the expression of polo‐like kinase 1 (PLK1) and phosphorylated protein kinase B (p‐AKT) was decreased. Overexpression of PLK1 partly rescued LPS‐induced apoptosis, proliferation suppression and atrophy in C2C12 cells. Furthermore, inhibiting the AKT pathway deteriorated LPS‐induced atrophy in PLK1‐overexpressing C2C12 myotubes. PLK1 was found to participate in regulating apoptosis and E3 ubiquitin ligase activity in C2C12 cells. Taken together, these results indicate that sepsis induces skeletal muscle atrophy by promoting apoptosis of muscle fibres and inhibiting proliferation of myoblasts via regulation of the PLK1‐AKT pathway. These findings enhance understanding of the mechanism of sepsis‐induced skeletal muscle atrophy.

As the first rate-limiting enzyme in fatty acid oxidation (FAO), CPT1 plays a significant role in metabolic adaptation in cancer pathogenesis. FAO provides an alternative energy supply for cancer cells and is required for cancer cell survival. Given the high proliferation rate of cancer cells, nucleotide synthesis gains prominence in rapidly proliferating cells. In the present study, we found that CPT1A is a determining factor for the abnormal activation of FAO in nasopharyngeal carcinoma (NPC) cells. CPT1A is highly expressed in NPC cells and biopsies. CPT1A dramatically affects the malignant phenotypes in NPC, including proliferation, anchorage-independent growth, and tumor formation ability in nude mice. Moreover, an increased level of CPT1A promotes core metabolic pathways to generate ATP, inducing equivalents and the main precursors for nucleotide biosynthesis. Knockdown of CPT1A markedly lowers the fraction of 13 C-palmitate-derived carbons into pyrimidine. Periodic activation of CPT1A increases the content of nucleoside metabolic intermediates promoting cell cycle progression in NPC cells. Targeting CPT1A-mediated FAO hinders the cell cycle G1/S transition. Our work verified that CPT1A links FAO to cell cycle progression in NPC cellular proliferation, which supplements additional experimental evidence for developing a therapeutic mechanism based on manipulating lipid metabolism.

Macrophages are widely distributed innate immune cells that play indispensable roles in the innate and adaptive immune response to pathogens and in-tissue homeostasis. Macrophages can be activated by a variety of stimuli and polarized to functionally different phenotypes. Two distinct subsets of macrophages have been proposed, including classically activated (M1) and alternatively activated (M2) macrophages. M1 macrophages express a series of proinflammatory cytokines, chemokines, and effector molecules, such as IL-12, IL-23, TNF-α, iNOS and MHCI/II. In contrast, M2 macrophages express a wide array of anti-inflammatory molecules, such as IL-10, TGF-β, and arginase1. In most tumors, the infiltrated macrophages are considered to be of the M2 phenotype, which provides an immunosuppressive microenvironment for tumor growth. Furthermore, tumor-associated macrophages secrete many cytokines, chemokines, and proteases, which promote tumor angiogenesis, growth, metastasis, and immunosuppression. Recently, it was also found that tumor-associated macrophages interact with cancer stem cells. This interaction leads to tumorigenesis, metastasis, and drug resistance. So mediating macrophage to resist tumors is considered to be potential therapy.

Cluster-based functional materials have made remarkable progress owing to their wonderful structures and distinctive physicochemical performances, one of on-going advancements of which is basically driven by synthetic chemistry of exploring and constructing novel nanosized gigantic polyoxometalate (POM) aggregates. In this article, an unprecedented nanoscale hexameric arsenotungstate aggregate Na 9 K 16 H 4 [Er 0.5 K 0.5 (H 2 O) 7 ][Er 5 W 10 O 26 (H 2 O) 14 ][B- α -AsW 9 O 33 ] 6 ·102H 2 O ( 1 ) has been synthesized by the combined synthetic strategy of simultaneously using the arsenotungstate precursor and simple tungstate material in a highly acidic aqueous solution. The {[Er 5 W 10 O 26 (H 2 O) 14 ][B-α-AsW 9 O 33 ] 6 } 31− polyanion in 1 consists of an intriguing dumbbell-shaped pentadeca-nuclear W-Er heterometal {Er 5 W 10 O 26 (H 2 O) 14 } 23+ cluster connecting six trilacunary [B-α-AsW 9 O 33 ] 9− moieties, which has never been seen previously. Furthermore, through electropolymerization of 1 and pyrrole on the conductive substrate, a thickness-controllable and robust 1 -PPY (PPY = polypyrrole) hybrid film was successfully prepared, which represents the first POM-PPY film assembled from high-nuclear lanthanide (Ln) encapsulated POM and PPY hitherto. The 1 -PPY film-based electrochemical biosensor exhibits a favorable recognition performance for ochratoxin A in multiple media. This work not only provides a feasible combined synthetic strategy of the POM precursor and simple tungstate material for constructing complicated multi-Ln-inserted POM aggregates, but also offers a promising electrochemical platform constructed from POM-based conductive films for identifying trace biomolecules in complex environments.

Male diabetic individuals present a marked impairment in fertility; however, knowledge regarding the pathogenic mechanisms and therapeutic strategies is unsatisfactory. The new hypoglycemic drug dapagliflozin has shown certain benefits, such as decreasing the risk of cardiovascular and renal events in patients with diabetes. Even so, until now, the effects and underlying mechanisms of dapagliflozin on diabetic male infertility have awaited clarification. Here, we found that dapagliflozin lowered blood glucose levels, alleviated seminiferous tubule destruction, and increased sperm concentrations and motility in leptin receptor-deficient diabetic db/db mice. Moreover, the glucagon-like peptide-1 receptor (GLP-1R) antagonist exendin (9-39) had no effect on glucose levels but reversed the protective effects of dapagliflozin on testicular structure and sperm quality in db/db mice. We also found that dapagliflozin inhibited the testicular apoptotic process by upregulating the expression of the antiapoptotic protein B-cell lymphoma 2 (BCL2) and X-linked inhibitor of apoptosis protein (XIAP) and inhibiting oxidative stress by enhancing the antioxidant status, including total antioxidant capacity, total superoxide dismutase (SOD) activity, and glutathione peroxidase (GPx) activity, as well as decreasing the level of 4-hydroxynonenal (4-HNE). Exendin (9-39) administration partially reversed these effects. Furthermore, dapagliflozin upregulated the glucagon-like peptide-1 (GLP-1) level in plasma and GLP-1R expression by promoting AKT8 virus oncogene cellular homolog (Akt) phosphorylation in testicular tissue. Exendin (9-39) partially inhibited Akt phosphorylation. These results suggest that dapagliflozin protects against diabetes-induced spermatogenic dysfunction via activation of the GLP-1R/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Our results indicate the potential effects of dapagliflozin against diabetes-induced spermatogenic dysfunction.

De-domestication is a unique evolutionary process by which domesticated crops are converted into ‘wild predecessor like’ forms. Weedy rice ( Oryza sativa f. spontanea ) is an excellent model to dissect the molecular processes underlying de-domestication. Here, we analyse the genomes of 155 weedy and 76 locally cultivated rice accessions from four representative regions in China that were sequenced to an average 18.2 × coverage. Phylogenetic and demographic analyses indicate that Chinese weedy rice was de-domesticated independently from cultivated rice and experienced a strong genetic bottleneck. Although evolving from multiple origins, critical genes underlying convergent evolution of different weedy types can be found. Allele frequency analyses suggest that standing variations and new mutations contribute differently to japonica and indica weedy rice. We identify a Mb-scale genomic region present in weedy rice but not cultivated rice genomes that shows evidence of balancing selection, thereby suggesting that there might be more complexity inherent to the process of de-domestication. De-domestication is the process by which cultivated plants adopt characteristics similar to that of their wild predecessors. Here Qiu et al . re-sequence de-domesticated weedy rice and matched cultivated varieties and identify genetic variants indicative of convergent evolution across multiple de-domestication events.