Abstract Metastasis accounts for 90% of cancer-related deaths among the patients. The transformation of epithelial cells into mesenchymal cells with molecular alterations can occur during epithelial–mesenchymal transition (EMT). The EMT mechanism accelerates the cancer metastasis and drug resistance ability in human cancers. Among the different regulators of EMT, Wnt/β-catenin axis has been emerged as a versatile modulator. Wnt is in active form in physiological condition due to the function of GSK-3β that destructs β-catenin, while ligand–receptor interaction impairs GSK-3β function to increase β-catenin stability and promote its nuclear transfer. Regarding the oncogenic function of Wnt/β-catenin, its upregulation occurs in human cancers and it can accelerate EMT-mediated metastasis and drug resistance. The stimulation of Wnt by binding Wnt ligands into Frizzled receptors can enhance β-catenin accumulation in cytoplasm that stimulates EMT and related genes upon nuclear translocation. Wnt/β-catenin/EMT axis has been implicated in augmenting metastasis of both solid and hematological tumors. The Wnt/EMT-mediated cancer metastasis promotes the malignant behavior of tumor cells, causing therapy resistance. The Wnt/β-catenin/EMT axis can be modulated by upstream mediators in which non-coding RNAs are main regulators. Moreover, pharmacological intervention, mainly using phytochemicals, suppresses Wnt/EMT axis in metastasis suppression. Graphical abstract 

Wnt/β-catenin-driven EMT regulation in human cancers

Objective Hyperglycemia and insulin resistance or deficiency are characteristic features of diabetes. Diabetes is accompanied by cardiomyocyte hypertrophy, fibrosis and ventricular remodeling, and eventually heart failure. In this study, we established a diabetic cardiomyopathy (DCM) mouse model to explore the role and mechanism of miR-200a-3p in DCM. Methods We used db/db mice to simulate the animal model of DCM and the expression of miR-200a-3p was then examined by RT-qPCR. Tail vein injection of mice was done with rAAV-miR-200a-3p for 8 weeks, and cardiac function was assessed by cardiac ultrasound. The levels of myocardial tissue injury, fibrosis, inflammation, apoptosis and autophagy in mice were detected by histological staining, TUNEL and other molecular biological experiments. Results miR-200a-3p expression levels were significantly decreased in the myocardium of DCM mice. Diabetic mice developed cardiac dysfunction and presented pathological changes such as myocardial injury, myocardial interstitial fibrosis, cardiomyocyte apoptosis, autophagy, and inflammation. Overexpression of miR-200a-3p expression significantly ameliorated diabetes induced-cardiac dysfunction and myocardial injury, myocardial interstitial fibrosis, cardiomyocyte apoptosis, and inflammation, and enhanced autophagy. Mechanistically, miR-200a-3p interacted with FOXO3 to promote Mst1 expression and reduce Sirt3 and p-AMPK expression. Conclusion In type 2 diabetes, increased miR-200a-3p expression enhanced autophagy and participated in the pathogenic process of cardiomyopathy throug7 Mst1/Sirt3/AMPK axis regulation by its target gene FOXO3. This conclusion provides clues for the search of new gene targeted therapeutic approaches for diabetic cardiomyopathy.

miR-200a-3p overexpression alleviates diabetic cardiomyopathy injury in mice by regulating autophagy through the FOXO3/Mst1/Sirt3/AMPK axis

Straw mushroom (Volvariella volvacea) is one of most extensively cultivated mushrooms in Asia with a delicious taste and high nutritional value. However, its special physiological features lead to the rapid loss of its overall quality and marketability during 2-day storage. The present study proposed an accessible and low-cost strategy with industrial-scale potency for long-time postharvest and long-distance distribution by designing a temperature and humidity-controlled walk-in equipment and optimizing the working conditions. The optimized conditions for postharvest with the designed equipment were obtained as pre-cooling treatment at 20 ℃, small size of plastic basket, one-layer stack mode, storage temperature of 15 °C and relative humidity of 90%. Under these conditions, the straw mushrooms maximally maintained the overall sensory/physical/chemical postharvest quality including highest firmness, soluble protein and soluble sugar contents. Further results proved that the optimized conditions maintained the quality by retaining free water, down-regulating the respiration rate and activities/transcriptional levels of key enzymes associated with respiratory metabolism, and maintaining the energy balance in fruiting bodies. 

Improving overall postharvest quality of straw mushroom using an accessible and low-cost strategy

As an important nutrient in the human body, cholesterol can not only provide structural components for the body's cells, but also can be transformed into a variety of active substances to regulate cell signaling pathways. As an important cholesterol synthase, DHCR24 participates in important regulatory processes in the body. The application of DHCR24 in tumor clinical diagnosis and treatment also attracts much attention. This article reviews the structure and regulatory characteristics of DHCR24, and the research of DHCR24 on tumor progression. We summarize the possible mechanisms of DHCR24 promoting tumor progression through reactive oxygen species (ROS), p53, Ras and PI3K-AKT pathways. Through our review, we hope to provide more research ideas and reference value for the application of DHCR24 in tumor prevention and treatment.

DHCR24 in Tumor Diagnosis and Treatment: A Comprehensive Review

Mitochondrial ribosomal protein L19 (MRPL19) is a member of the mitochondrial ribosomal protein (MRP) family. MRPs have a role in the progression of many cancers. However, the role of MRPL19 in lung adenocarcinoma (LUAD) is yet unknown.The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, real-time polymerase chain reaction, and immunohistochemistry (IHC) were used to assess MRPL19 expression and clinical relevance. Gene Expression Profiling Interactive Analysis (GEPIA) and the online Kaplan-Meier (KM) Plotter database were used to determine the prognostic significance. Through use of LinkedOmics, genes that were coexpressed with MRPL19 and its regulators were identified. The biological roles of MRPL19 were investigated through R-implemented packages and RNA interference. The Tumor Immune Estimation Resource (TIMER) was employed to assess the connection between MRPL19 expression and infiltrated immune cells in LUAD.MRPL19 expression in LUAD was upregulated and was correlated with lymph node metastasis, differentiation level, and tumor status. MRPL19 was prognostic and associated with poor prognosis. Functional network analysis revealed that MRPL19 may be associated with the cell cycle, cell adhesion molecules, spliceosome, and T-helper cell differentiation and was regulated by several microRNA and the E2F family. The gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network indicated that MRPL19 was correlated with cancer proliferation signaling pathways. The immune infiltration analysis revealed a correlation between MRPL19 expression and the extent of B cells, CD4+ T cells, and dendritic cells' infiltration in LUAD. Additionally, MRPL19 knockdown in LUAD cells substantially reduced cell growth, migration, and invasion of malignant cells.The poor prognosis and immunological infiltration in LUAD were significantly associated with MRPL19, which may have pro-oncogenic effects on the disease. 

Overexpression of MRPL19 in predicting poor prognosis and promoting the development of lung adenocarcinoma

Lung cancer has high mortality and incidence rates in which non‐small cell lung cancer (NSCLC) is the primary type of lung cancer that accounts for about 80%–85% of total patients. It has been demonstrated that microRNAs (miRNAs) are critical in the incidence and progression of tumors, while the role and inner mechanism of miR‐200a‐3p, one type of essential miRNAs, in NSCLC have yet to be revealed. Herein, we investigated the in vitro and vivo pro‐/antiproliferative influence of miR‐200a‐3p on NSCLC cells and utilized bioinformatic programs to further predict the SOX17 gene as miR‐200a‐3p's potential target. A double luciferase reporter gene experiment was performed to confirm that miR‐200a‐3p interacts with the SOX17 3ʹ‐UTR region specifically. On the basis of the results of Western blot and quantitative reverse‐transcription polymerase chain reaction (qRT‐PCR), miR‐200a‐3p impacted the posttranscriptional levels of SOX17 rather than influencing its mRNA expression. In the end, we found that overexpressed SOX17 can reverse miR‐200a‐3p's impact on NSCLC cell proliferation and metastasis. Therefore, this study demonstrated that miR‐200a‐3p influences NSCLC cell proliferation and metastasis by modulating the levels of SOX17.

miR‐200a‐3p promoted cell proliferation and metastasis by downregulating SOX17 in non‐small cell lung cancer cells

Volvariella volvacea, the edible straw mushroom, is popular among consumers; however, its freshness is difficult to maintain at 4 °C. Spray treatment with the ubiquitin-binding enzyme E2 (UBEV2) inhibitor L345-0044 maintained the freshness of V. volvacea during storage at 4 °C for 48 h. Inhibitor treatment enhanced the ability of V. volvacea to resist cold stress by inducing overexpression of genes involved in protein translation, protein turnover, N-glycan biosynthesis, and lysine metabolism. Overexpression of saccharopine dehydrogenase genes, which participate in lysine metabolism in yeast, enhanced freezing tolerance. Anti-freezing experiments showed that the addition of l-lysine or l-threonine improved the quality of V. volvacea at 4 °C with stable soluble sugar levels, as lysine or threonine metabolism produced acetyl-CoA for maintaining the citrate cycle. Our findings revealed that supplementation with l-lysine or l-threonine prolonged the preservation time of V. volvacea for more than 24 h via maintenance of the citrate cycle. 

Lysine and threonine supplementation promotes postharvest quality of Volvariella volvacea mushroom during low-temperature preservation via maintenance of the citrate cycle

Long noncoding RNAs (lncRNAs) are critically involved in the occurrence and development of breast cancer (BC). In this study, we performed RNA sequencing, and the results revealed an increase in the expression level of novel lncRNA ENST00000370438 in tissues of patients with BC. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR) results showed an increase in lncRNA ENST00000370438 expression level in 23 pairs of BC tissues. Next, we determined the effect of ENST00000370438 on BC cell proliferation, and the results showed that ENST00000370438 promotes cell proliferation in BC. The proteomic analysis showed a decrease in DHCR24 expression level in BC cells transfected with ENST00000370438 small interfering RNA. Western blot and qRT‐PCR assay results showed that ENST00000370438 regulated DHCR24 expression. Furthermore, the rescue experiment showed that the interference with ENST00000370438 expression could restore the effect of DHCR24 overexpression on BC cell proliferation, demonstrating that ENST00000370438 could promote cell proliferation by upregulating DHCR24. Finally, we showed that lncRNA ENST000000370438 could promote tumor growth by overexpressing DHCR24 in nude mice. Our results demonstrated that lncRNA ENST00000370438 promotes BC cell proliferation by upregulating DHCR24 expression.

LncRNA ENST00000370438 promotes cell proliferation by upregulating DHCR24 in breast cancer

The serine/threonine protein kinase VSKM1 promotes cold stress resistance of the postharvest Volvariella volvacea by enhancing mitoribosome activity

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miR‐200a‐3p promoted cell proliferation and metastasis by downregulating SOX17 in non‐small cell lung cancer cells

Lysine and threonine supplementation promotes postharvest quality of Volvariella volvacea mushroom during low-temperature preservation via maintenance of the citrate cycle

LncRNA ENST00000370438 promotes cell proliferation by upregulating DHCR24 in breast cancer

The serine/threonine protein kinase VSKM1 promotes cold stress resistance of the postharvest Volvariella volvacea by enhancing mitoribosome activity