Insights into the efficient degradation mechanism of extracellular proteases mediated by Purpureocillium lilacinum.

Protease secretion is crucial for degrading nematode cuticles using nematophagous fungus Purpureocillium lilacinum, but the secretion pattern of protease remains poorly understood. This study aimed to explore the degradation mechanism of proteases by investigating the characteristics of protease secretion under various carbon and nitrogen sources, and different carbon to nitrogen (C:N) ratios in P. lilacinum. The results showed that corn flour as a carbon source and yeast extract as a nitrogen source specifically induced protease secretion in P. lilacinum. P. lilacinum produced significant amounts of gelatinase and casein enzyme at C:N ratios of 10:1, 20:1, and 40:1, indicating that higher C:N ratios were more beneficial for secreting extracellular proteases. Proteomic analysis revealed 14 proteases, including 4 S8 serine endopeptidases and one M28 aminopeptidase. Among four S8 serine peptidases, Alp1 exhibited a high secretion level at C:N ratio less than 5:1, whereas PR1C, PR1D, and P32 displayed higher secretion levels at higher C:N ratios. In addition, the transcription levels of GATA transcription factors were investigated, revealing that Asd-4, A0A179G170, and A0A179HGL4 were more prevalent at a C:N ratio of 40:1. In contrast, the transcription levels of SREP, AreA, and NsdD were higher at lower C:N ratios. The putative regulatory profile of extracellular protease production in P. lilacinum, induced by different C:N ratios, was analyzed. The findings offered insights into the complexity of protease production and aided in the hydrolytic degradation of nematode cuticles.

Insights into the microbial assembly and metabolites associated with ginger (Zingiber officinale L. Roscoe) microbial niches and agricultural environments.

Ginger, a vegetable export from China, is well-known for its spicy flavour and use in traditional Chinese medicine. By examining the interactions of ginger plants' microbiome and metabolome, we can gain insights to advance agriculture, the environment, and other fields. Our study used metataxonomic analysis to investigate ginger plants' prokaryotic and fungal microbiomes in open fields and greenhouses. We also conducted untargeted metabolomic analysis to identify specific metabolites closely associated with ginger microbiome assembly under both agricultural conditions. Various bacteria and fungi were classified as generalists or specialists based on their ability to thrive in different environments and microbial niches. Our results indicate that ginger plants grown in greenhouses have a greater prokaryotic diversity, while those grown in open fields exhibit a greater fungal diversity. We have identified specific co-occurring prokaryotic and fungal genera associated with ginger plant agroecosystems that can enhance the health and growth of ginger plants while maintaining a healthy environment. In the open field these genera include Sphingomonas, Methylobacterium-Methylorubrum, Bacillus, Acidovorax, Rhizobium, Microbacterium, unclassified_f_Comamonadaceae, Herbaspirillum, Klebsiella, Enterobacter, Chryseobacterium, Nocardioides, Subgroup_10, Enterococcus, Pseudomonas, Devosia, g_unclassified_f_Chaetomiaceae, Pseudaleuria, Mortierella, Cheilymenia, and Pseudogymnoascus. In the greenhouse, the enriched genera were Rhizobium, Stenotrophomonas, Aureimonas, Bacillus, Nocardioides, Pseudomonas, Enterobacter, Delftia, Trichoderma, Mortierella, Cheilymenia, Schizothecium, and Actinomucor. Our research has identified several previously unknown microbial genera for ginger plant agroecosystems. Furthermore, our study has important implications for understanding the correlation between ginger's microbiome and metabolome profiles in diverse environments and may pave the way for future research. Specific microbial genera in crop production environments are associated with essential metabolites, including Safingol, Docosatrienoic acid, P-acetaminophen, and Hypoglycin B.

Polychlorinated biphenyls exposure and type 2 diabetes: Molecular mechanism that causes insulin resistance and islet damage.

Polychlorinated biphenyls (PCBs) are typical persistent organic pollutants that have been associated with type 2 diabetes (T2DM) in cohort studies. This review aims to comprehensively assess the molecular mechanisms of PCBs-induced T2DM. Recent progress has been made in the research of PCBs in liver tissue, adipose tissue, and other tissues. By influencing the function of nuclear receptors, such as the aryl hydrocarbon receptor (AhR), pregnancy X receptor (PXR), and peroxisome proliferator activated receptor γ (PPARγ), as well as the inflammatory response, PCBs disrupt the balance of hepatic glucose and lipid metabolism. This is associated with insulin resistance (IR) in the target organ of insulin. Through androgen receptor (AR), estrogen receptor α/ß (ERα/ß), and pancreato-duodenal-homeobox gene-1 (PDX-1), PCBs affect the secretion of insulin and increase blood glucose. Thus, this review is a discussion on the relationship between PCBs exposure and the pathogenesis of T2DM. It is hoped to provide basic concepts for diabetes research and disease treatment.

Genome-Wide and Transcriptome Analysis of Jacalin-Related Lectin Genes in Barley and the Functional Characterization of HvHorcH in Low-Nitrogen Tolerance in Arabidopsis.

The jacalin-related lectins (JRLs) are widely distributed in plants and are involved in plant development and multiple stress responses. However, the characteristics of the HvJRL gene family at the genome-wide level and the roles of JRLs in barley's response to low-nitrogen (LN) stress have been rarely reported. In this study, 32 HvJRL genes were identified and unevenly distributed at both ends of the seven chromosomes in barley. HvJRL proteins generally exhibited low sequence similarity but shared conserved jacalin domains by multiple sequence analysis. These proteins were classified into seven subfamilies based on phylogenetic analysis, with a similar gene structure and conserved motifs in the same subfamily. The HvJRL promoters contained a large number of diverse cis-elements associated with hormonal response and stress regulation. Based on the phylogenetic relationships and functionally known JRL homologs, it was predicted that some HvJRLs have the potential to serve functions in multiple stress responses but not nutrition deficiency stress. Subsequently, nine differentially expressed genes (DEGs) encoding eight HvJRL proteins were identified in two barley genotypes with different LN tolerance by transcriptome analysis. Furthermore, 35S:HvHorcH transgenic Arabidopsis seedlings did enhance LN tolerance, which indicated that HvHorcH may be an important regulator of LN stress response (LNSR). The HvJRL DEGs identified herein could provide new candidate genes for LN tolerance studies.

PIK3CD correlates with prognosis, epithelial-mesenchymal transition and tumor immune infiltration in breast carcinoma.

BACKGROUND: Breast carcinoma (BRCA) is one of the most common, fatal, and aggressive cancers, with increasing morbidity that has a major impact on human health. PIK3CD appears to have important roles in the beginning and advancement of various forms of human cancer, according to mounting data. However,the particular role and mechanism of PIK3CD in BRCA remains not fully identified. METHODOLOGY: The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov/ ), Genotype-Tissue Expression (GTEx) data and the UCSC Xena browser ( https://xenabrowser.net ) data were used in this study's initial pan-cancer analysis of PIK3CD expression and prognosis. Circular RNAs (circRNAs) that regulated the expression of PIK3CD were subsequently found using a combination of in silico investigations of expression, correlation, and survival. Measurements of PIK3CD expression and an analysis of the in vitro function of PIK3CD in BRCA cells were performed using real-time RT-PCR, Western blotting and Transwell assays. RESULTS: In BRCA GLI2, RAB32, LAMB1, MGAT2, ITGA8, CHF, COL6A3 and PRRX1-miR-30b-5p axis was identified as the most likely upstream CircRNA-related route of PIK3CD. PIK3CD was correlated with the expression of EMT markers. The PIK3CD cDNA improved the capacity for invasion and migration. The expression of PIK3CD was linked to some of the m1A/m5C/m6A regulators. Additionally, it was discovered that the expression of PIK3CD was found to be highly connected to the expression of immunological checkpoints, immune cell biomarkers, and tumor immune cell invasion. CONCLUSIONS: Our findings reveal that PIK3CD expression is associated with prognosis, EMT, and tumor immune infiltration in BRCA patients.

A new avialan theropod from an emerging Jurassic terrestrial fauna.

Birds are descended from non-avialan theropod dinosaurs of the Late Jurassic period, but the earliest phase of this evolutionary process remains unclear owing to the exceedingly sparse and spatio-temporally restricted fossil record1-5. Information about the early-diverging species along the avialan line is crucial to understand the evolution of the characteristic bird bauplan, and to reconcile phylogenetic controversies over the origin of birds3,4. Here we describe one of the stratigraphically youngest and geographically southernmost Jurassic avialans, Fujianvenator prodigiosus gen. et sp. nov., from the Tithonian age of China. This specimen exhibits an unusual set of morphological features that are shared with other stem avialans, troodontids and dromaeosaurids, showing the effects of evolutionary mosaicism in deep avialan phylogeny. F. prodigiosus is distinct from all other Mesozoic avialan and non-avialan theropods in having a particularly elongated hindlimb, suggestive of a terrestrial or wading lifestyle-in contrast with other early avialans, which exhibit morphological adaptations to arboreal or aerial environments. During our fieldwork in Zhenghe where F. prodigiosus was found, we discovered a diverse assemblage of vertebrates dominated by aquatic and semi-aquatic species, including teleosts, testudines and choristoderes. Using in situ radioisotopic dating and stratigraphic surveys, we were able to date the fossil-containing horizons in this locality-which we name the Zhenghe Fauna-to 148-150 million years ago. The diversity of the Zhenghe Fauna and its precise chronological framework will provide key insights into terrestrial ecosystems of the Late Jurassic.

Recent advances in pyroptosis, liver disease, and traditional Chinese medicine: A review.

In recent years, the incidence of liver disease has increased, becoming a major cause of death. Various liver diseases are intricately linked to pyroptosis, which is one of the most common forms of programmed cell death. As a powerful weapon in the fight against liver diseases, traditional Chinese medicine (TCM) can affect pyroptosis via a number of routes, including the classical, nucleotide oligomerization domain-like receptors protein 3/caspase-1/gasdermin D (GSDMD) pathway, the nonclassical lipopolysaccharide/caspase-11/GSDMD pathway, the ROS/caspase-3/gasdermin E pathway, the caspase-9/caspase-3/GSDMD pathway, and the Apaf-1/caspase-11/caspase-3 pathway. In this review, we provide an overview of pyroptosis, the interplay between pyroptosis and liver diseases, and the mechanisms through which TCM regulates pyroptosis in liver diseases. The information used in the text was collected and compiled from the databases of PubMed, Web of Science, Scopus, CNKI, and Wanfang Data up to June 2023. The search was not limited with regard to the language and country of the articles. Research and review articles were included, and papers with duplicate results or unrelated content were excluded. We examined the current understanding of the relationship between pyroptosis and liver diseases as well as the advances in TCM interventions to provide a resource for the identification of potential targets for TCM in the treatment of liver diseases.

Identification of LsLAZY1 gene in Leymus secalinus and validation of its function in Arabidopsis thaliana.

Root systems anchor plants to the substrate in addition to transporting water and nutrients, playing a fundamental role in plant survival. The LAZY1 gene mediates gravity signal transduction and participates in root and shoot development and auxin flow in many plants. In this study, a regulator, LsLAZY1, was identified from Leymus secalinus based on previous transcriptome data. The conserved domain and evolutionary relationship were further analyzed comprehensively. The role of LsLAZY1 in root development was investigated by genetic transformation and associated gravity response and phototropism assay. Subcellular localization showed that LsLAZY1 was localized in the nucleus. LsLAZY1 overexpression in Arabidopsis thaliana (Col-0) increased the length of the primary roots (PRs) and the number of lateral roots (LRs) compared to Col-0. Furthermore, 35S:LsLAZY1 transgenic seedlings affected auxin transport and showed a stronger gravitational and phototropic responses. It also promoted auxin accumulation at the root tips. These results indicated that LsLAZY1 affects root development and auxin transport. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01326-4.

Nicotinamide mononucleotide improves the Alzheimer's disease by regulating intestinal microbiota.

Alzheimer's disease (AD) is the most common progressive neurodegenerative disease, and the intestinal flora and its metabolites play an important role in the amelioration of central nervous system (CNS) disorders such as AD through a bidirectional interaction between the gut-brain axis (GBA). Nicotinamide mononucleotide (NMN), one of the precursors for nicotinamide adenine dinucleotide (NAD+) synthesis, reduces the brain features of AD, including neuroinflammation, mitochondrial abnormalities, synaptic dysfunction, and cognitive impairment. However, the impact of NMN on the gut flora of AD is still unknown. In the current study, we investigated the relationship between gut flora and NMN treatment in APP/PS1 transgenic (AD) mice through the 16S ribosomal RNA (rRNA) high-throughput sequencing analysis of mouse feces after being treated with NMN for 16 weeks. The results show that the NMN significantly changed the intestinal microbial community composition in AD mice. The NMN also increased the relative abundance of short-chain fatty acids (SCFAs)-producing bacteria such as Lactobacillus and Bacteroides at the genus level by protecting intestinal health and improving AD. The overall results suggest novel therapeutic strategies for treating AD and highlight the critical role of gut microbiota in AD pathology, and layout the further research.

Genome-Wide Analysis of Barley bHLH Transcription Factors and the Functional Characterization of HvbHLH56 in Low Nitrogen Tolerance in Arabidopsis.

Improvement of low nitrogen (LN) tolerance or nitrogen use efficiency (NUE) in crops is imperative for environment-friendly agriculture development. The basic helix-loop-helix (bHLH) transcription factors are involved in multiple abiotic stresses and are suitable as candidate genes for improving LN tolerance. Few studies were performed on the characterization of the HvbHLH gene family and their function in response to LN stress in barley. In this study, 103 HvbHLH genes were identified through genome-wide analysis. HvbHLH proteins were classified into 20 subfamilies based on phylogenetic analysis in barley, which was supported by conserved motifs and gene structure analysis. The stress-related cis-element analysis in the promoters showed that HvbHLHs are probably involved in multiple stress responses. By phylogenetic analysis of HvbHLHs and bHLHs in other plants, some HvbHLHs were predicted to play roles in response to nutrition deficiency stress. Furthermore, at least 16 HvbHLHs were differentially expressed in two barley genotypes differing in LN tolerance under LN stress. Finally, overexpression of HvbHLH56 enhanced LN stress tolerance in transgenic Arabidopsis, suggesting it is an important regulator in LN stress response. The differentially expressed HvbHLHs identified herein may be valuable for the breeding of barley cultivars with LN tolerance.

ZmEREB57 regulates OPDA synthesis and enhances salt stress tolerance through two distinct signalling pathways in Zea mays.

In plant, APETALA2/ethylene-responsive factor (AP2/ERF)-domain transcription factors are important in regulating abiotic stress tolerance. In this study, ZmEREB57 encoding a AP2/ERF transcription factor was identified and its function was investigated in maize. ZmEREB57 is a nuclear protein with transactivation activity induced by several abiotic stress types. Furthermore, two CRISPR/Cas9 knockout lines of ZmEREB57 showed enhanced sensitivity to saline conditions, whereas the overexpression of ZmEREB57 increased salt tolerance in maize and Arabidopsis. DNA affinity purification sequencing (DAP-Seq) analysis revealed that ZmEREB57 notably regulates target genes by binding to promoters containing an O-box-like motif (CCGGCC). ZmEREB57 directly binds to the promoter of ZmAOC2 involved in the synthesis of 12-oxo-phytodienoic acid (OPDA) and jasmonic acid (JA). Transcriptome analysis revealed that several genes involved in regulating stress and redox homeostasis showed differential expression patterns in OPDA- and JA-treated maize seedlings exposed to salt stress compared to those treated with salt stress alone. Analysis of mutants deficient in the biosynthesis of OPDA and JA revealed that OPDA functions as a signalling molecule in the salt response. Our results indicate that ZmEREB57 involves in salt tolerance by regulating OPDA and JA signalling and confirm early observations that OPDA signalling functions independently of JA signalling.

KLF14/miR-1283/TFAP2C axis inhibits HER2-positive breast cancer progression via declining tumor cell proliferation.

MiR-1283 has been identified as a tumor suppressor in some malignancies. Whereas, the role of miR-1283 in HER2-positive (HER2+) breast cancer, particularly its role in regulating cell proliferation, one of the most significant features of tumor progression, is unclear. The related microRNA screened by the breast cancer sample GSE131599 dataset were detected in HER2+ breast cancer tissues and cell lines. Then, the obtained miR-1283 was overexpressed in SKBR3 and BT-474 cells followed by relevant functional assays concerning cell proliferation and apoptosis. The xenograft mouse model was induced and the effect of miR-1283 on tumor growth and cell proliferation was examined. The target of miR-1283 and the transcription factor regulating miR-1283 were predicted and identified. Finally, the influence of transcription factor KLF14 on cell proliferation and apoptosis was investigated. An integrated analysis confirmed that miR-1283 expression was significantly decreased in HER2+ breast cancer tissues. Also, by q-RT-PCR detection, miR-1283 expression was markedly reduced in HER2+ breast cancer tissues and cell lines. The miR-1283 overexpression prevented the proliferation and enhanced apoptosis of HER2+ breast cancer cells, as well as inhibited tumor growth. Mechanistically, miR-1283 inhibited TFAP2C expression by targeting the 3'-untranslated regions of TFAP2C messenger RNA, and the KLF14 enhanced miR-1283 level via binding to its promoter. The result subsequently confirmed the KLF14/miR-1283 signaling suppressed cell proliferation in HER2+ breast cancer. Our results suggested that the KLF14/miR-1283/TFAP2C axis inhibited HER2+ breast cancer progression, which might provide novel insight into mechanical exploration for this disease.

Comprehensive analysis of cucumber RAV family genes and functional characterization of CsRAV1 in salt and ABA tolerance in cucumber.

The RAV (related to ABI3 and VP1) transcription factors are specific and exist in plants, which contain a B3 DNA binding domain and/or an APETALA2 (AP2) DNA binding domain. RAVs have been extensively studied in plants, and more and more evidences show that RAVs are involved in various aspects of plant growth and development, stress resistance and hormone signal transduction. However, the systematic analysis of RAV family in cucumber is rarely reported. In this study, eight CsRAV genes were identified in cucumber genome and we further comprehensively analyzed their protein physicochemical properties, conserved domains, gene structure and phylogenetic relationships. The synteny analysis and gene duplications of CsRAV genes were also analysed. Cis-element analysis revealed that the CsRAVs promoter contained several elements related to plant hormones and abiotic stress. Expression analysis showed that NaCl and ABA could significantly induce CsRAV genes expression. Subcellular localization revealed that all CsRAVs were localized in the nucleus. In addition, 35S:CsRAV1 transgenic Arabidopsis and cucumber seedlings enhanced NaCl and ABA tolerance, revealing CsRAV1 may be an important regulator of abiotic stress response. In conclusion, comprehensive analysis of CsRAVs would provide certain reference for understanding the evolution and function of the CsRAV genes.

Identification of LsPIN1 gene and its potential functions in rhizome turning of Leymus secalinus.

BACKGROUND: Continuous tilling and the lateral growth of rhizomes confer rhizomatous grasses with the unique ability to laterally expand, migrate and resist disturbances. They play key roles especially in degraded grasslands, deserts, sand dunes, and other fragile ecological system. The rhizomatous plant Leymus secalinus has both rhizome buds and tiller buds that grow horizontally and upward at the ends of rhizome differentiation and elongation, respectively. The mechanisms of rhizome formation and differentiation in L. secalinus have not yet been clarified. RESULTS: In this study, we found that the content of gibberellin A3 (GA3) and indole-3-acetic acid (IAA) were significantly higher in upward rhizome tips than in horizontal rhizome tips; by contrast, the content of methyl jasmonate and brassinolide were significantly higher in horizontal rhizome tips than in upward rhizome tips. GA3 and IAA could stimulate the formation and turning of rhizomes. An auxin efflux carrier gene, LsPIN1, was identified from L. secalinus based on previous transcriptome data. The conserved domains of LsPIN1 and the relationship of LsPIN1 with PIN1 genes from other plants were analyzed. Subcellular localization analysis revealed that LsPIN1 was localized to the plasma membrane. The length of the primary roots (PRs) and the number of lateral roots (LRs) were higher in Arabidopsis thaliana plants overexpressing LsPIN1 than in wild-type (Col-0) plants. Auxin transport was altered and the gravitropic response and phototropic response were stronger in 35S:LsPIN1 transgenic plants compared with Col-0 plants. It also promoted auxin accumulation in root tips. CONCLUSION: Our findings indicated that LsPIN1 plays key roles in auxin transport and root development. Generally, our results provide new insights into the regulatory mechanisms underlying rhizome development in L. secalinus.

Microbial Community, Co-Occurrence Network Relationship and Fermentation Lignocellulose Characteristics of Broussonetia papyrifera Ensiled with Wheat Bran.

Broussonetia papyrifera has a high lignocellulose content leading to poor palatability and low digestion rate of ruminants. Thus, dynamic profiles of fermentation lignocellulose characteristics, microbial community structure, potential function, and interspecific relationships of B. papyrifera mixing with wheat bran in different ratios: 100:0 (BP100), 90:10 (BP90), 80:20 (BP80), and 65:35 (BP65) were investigated on ensiling days 5, 15, 30, and 50. The results showed that adding bran increased the degradation rate of hemicellulose, neutral detergent fiber, and the activities of filter paper cellulase, endoglucanase, acid protease, and neutral protease, especially in the ratio of 65:35. Lactobacillus, Pediococcus, and Weissella genus bacteria were the dominant genera in silage fermentation, and Pediococcus and Weissella genus bacteria regulated the process of silage fermentation. Compared with monospecific B. papyrifera silage, adding bran significantly increased the abundance of Weissella sp., and improved bacterial fermentation potential in BP65 (p < 0.05). Distance-based redundancy analysis showed that lactic acid bacteria (LAB) were significantly positive correlated with most lignocellulose content and degrading enzymes activities, while Monascus sp. and Syncephalastrum sp. were opposite (p < 0.05). Co-occurrence network analysis indicated that there were significant differences in microbial networks among different mixing ratios of B. papyrifera silage prepared with bran. There was a more complex, highly diverse and less competitive co-occurrence network in BP65, which was helpful to silage fermentation. In conclusion, B. papyrifera ensiled with bran improved the microbial community structure and the interspecific relationship and reduced the content of lignocellulose.

Comprehensive analysis of cucumber C-repeat/dehydration-responsive element binding factor family genes and their potential roles in cold tolerance of cucumber.

BACKGROUND: Cold stress is one of the main abiotic stresses limiting cucumber (Cucumis sativus L.) growth and production. C-repeat binding factor/Dehydration responsive element-binding 1 protein (CBF/DREB1), containing conserved APETALA2 (AP2) DNA binding domains and two characteristic sequences, are key signaling genes that can be rapidly induced and play vital roles in plant response to low temperature. However, the CBF family has not been systematically elucidated in cucumber, and the expression pattern of this family genes under cold stress remains unclear. RESULTS: In this study, three CsCBF family genes were identified in cucumber genome and their protein conserved domain, protein physicochemical properties, gene structure and phylogenetic analysis were further comprehensively analyzed. Subcellular localization showed that all three CsCBFs were localized in the nucleus. Cis-element analysis of the promoters indicated that CsCBFs might be involved in plant hormone response and abiotic stress response. Expression analysis showed that the three CsCBFs could be significantly induced by cold stress, salt and ABA. The overexpression of CsCBFs in cucumber seedlings enhanced the tolerance to cold stress, and importantly, the transcript levels of CsCOR genes were significantly upregulated in 35S:CsCBFs transgenic plants after cold stress treatment. Biochemical analyses ascertained that CsCBFs directly activated CsCOR genes expression by binding to its promoter, thereby enhancing plant resistance to cold stress. CONCLUSION: This study provided a foundation for further research on the function of CsCBF genes in cold stress resistance and elucidating its mechanism.

LncRNA HOTAIR promotes the proliferation and invasion/metastasis of breast cancer cells by targeting the miR-130a-3p/Suv39H1 axis.

Long noncoding RNAs (lncRNAs) are a group of transcripts, more than 200 bp in size and regulate cell proliferation, differentiation and apoptosis. LncRNA HOX Transcript Antisense Intergenic RNA (HOTAIR) promotes tumor progression and increases cancer susceptibility by regulating microRNA expression and function. HOTAIR regulates miR-130a-3p expression in hepatocellular carcinoma cells. Bioinformatics analysis revealed that Suv39H1 contained a putative binding site for miR-130a-3p. We speculate that LncRNA HOTAIR promotes the proliferation and invasion/metastasis of breast cancer (BC) cells by targeting the miR-130a-3p/Suv39H1 axis. High HOTAIR expression facilitated BC cell growth and metastasis. HOTAIR functioned as a ceRNA by sponging miR-130a-3p and subsequently promoted Suv39H1-mediated AKT/mTOR signaling. Suv39H1 restoration abolished the effects of HOTAIR knockdown on BC cell growth and metastasis. HOTAIR facilitated the Suv39H1-mediated AKT/mTOR pathway by acting as a molecular sponge of miR-130a-3p.Our results provide a better understanding of the interactions of HOTAIR and miR-103a-3p/Suv39H1 in BC and a potential prognostic biomarker and therapeutic target for BC.

Covalent Biosensing Polymer Chain Reaction Enabling Periphery Blood Testing to Predict Tumor Invasiveness with a Platelet Procancerous Protein.

Periphery blood testing is an attractive and relatively less invasive way of early cancer screening. In this work, based on the latest understanding of the pivotal role of platelets in promoting cancer invasion, a method for detecting a procancerous protein overexpressed both on platelets and in cancer cells is developed. As a kinase, the enzymatic activity, abundance, and self-phosphorylation of this protein are all important factors influencing its procancerous activity. To simultaneously determine these three important biochemical parameters, electrochemical control is called upon to connect or disconnect a polymer chain reaction (PCR) primer with a small-molecule synthetic probe, and with the target protein, in a target-specific manner. The resulting PCR signal amplification greatly improves the sensitivity of the design and also enables direct detection of the protein and its catalytic activity as well as its self-phosphorylation in clinical periphery blood samples from hepatocellular carcinoma (HCC) patients. This may point to future application of the proposed method in the early screening of HCC to assist its diagnosis and treatment.

Circular RNA circ-ERBB2 promotes HER2-positive breast cancer progression and metastasis via sponging miR-136-5p and miR-198.

BACKGROUND: Circular RNAs (circRNAs) are pivotal regulators of various human cancers and circ-ERBB2 is abnormally expressed in breast cancer cells. However, the role and mechanism of circ-ERBB2 in HER2-positive breast cancer are still unknown. METHODS: The circ-ERBB2 expressions in the tumor tissues of HER2-positive breast cancer patients were tested using quantitative real-time PCR. The circ-ERBB2 function was investigated by cell counting kit 8 assay, Transwell, flow cytometry and Western blot. Mechanistically, fluorescence in situ hybridization, RNA immunoprecipitation, RNA pull-down and dual-luciferase reporter gene assays were conducted to confirm the interaction between circ-ERBB2 and miR-136-5p or miR-198 in HER2-positive breast cancer cells. RESULTS: Circ-ERBB2 was elevated in the tumor tissues of HER2-positive breast cancer patients. Functionally, the interference with circ-ERBB2 repressed HER2-positive breast cancer cell proliferation, migration, invasion and accelerated cell apoptosis. Furthermore, the mechanistic analysis corroborated that circ-ERBB2 acted as a competing endogenous RNA for miR-136-5p or miR-198 to relieve the repressive influence of miR-136-5p or miR-198 on its target transcription factor activator protein 2C (TFAP2C). Meanwhile, in vivo assays further corroborated the oncogenic function of circ-ERBB2 in HER2-positive breast cancer. CONCLUSIONS: Circ-ERBB2 accelerated HER2-positive breast cancer progression through the circ-ERBB2/miR-136-5p/TFAP2C axis or the circ-ERBB2/miR-198/TFAP2C axis.

miR­125a­5p reverses epithelial­mesenchymal transition and restores drug sensitivity by negatively regulating TAFAZZIN signaling in breast cancer.

MicroRNA (miR)­125a­5p represses tafazzin phospholipid­lysophospholipid transacylases (TAFAZZIN) expression and inhibits the epithelial­mesenchymal transition (EMT) of ovarian cancer cells. EMT was found to have a crucial role in the acquisition of chemoresistance. Thus, the present study aimed to determine whether miR­125a­5p reverses EMT and restores drug sensitivity by negatively regulating TAFAZZIN in breast cancer. The expression of miR­125a­5p/TAFAZZIN and its association with chemotherapy response were determined in tissue samples from patients with breast cancer. Furthermore, the effects of miR­125a­5p on breast cancer cells were elucidated using cell proliferation and cell apoptosis assays. Then, the regulatory mechanism of miR­125a­5p in breast cancer was investigated by reverse transcription­quantitative PCR, western blotting, dual­luciferase reporter and RNA immunoprecipitation assays. The results demonstrated that miR­125a­5p inhibited the EMT of MCF­7/adriamycin (Adr) breast cancer cells, as well as decreased the proliferation and increased the apoptosis of breast cancer cells treated with Adr/docetaxel. In addition, miR­125a­5p downregulated the expression levels of TAFAZZIN, Transglutaminase 2, phosphorylated­AKT, N­cadherin, vimentin and proliferating cell nuclear antigen, and significantly increased those of E­cadherin, cleaved caspase-3 and Bax in MCF7/Adr cells. Similar results were obtained with small interfering RNA­TAFAZZIN. Moreover, TAFAZZIN was identified as a direct target of miR­125a­5p in MCF7/Adr breast cancer cells. In addition, increased miR­125a­5p expression was observed in breast tumors from patients exhibiting a chemotherapy response, and TAFAZZIN mRNA expression was elevated in patients with no chemotherapy response. Hence, miR­125a­5p expression was negatively correlated with TAFAZZIN mRNA expression in breast cancer tissues. All these data suggested that miR­125a­5p reverses EMT and restores drug sensitivity by negatively regulating TAFAZZIN in breast cancer and, therefore, has potential as a novel therapeutic target for this disease.