Insights into two-phase flow dynamics in closed-loop pulsating heat pipes utilizing Fe3O4/water: experimental visualization study.

This article discusses a focused study on visualizing the flow patterns in a two-phase pulsating heat pipe (PHP) using Fe3O4/water as the working fluid at 3 V/V% concentration. The research also aims to meticulously examine phase change phenomena in the heating section, particularly focusing on bubble formation and expansion processes. A high-speed video camera was utilized to capture dynamic insights into the behavior of the Fe3O4/water mixture. Based on the findings, a straightforward model was developed to explain bubble generation and growth in the mixture, serving as a useful reference for future PHP designs and optimizations. Visual observations also noted the stable nature of the Fe3O4/water nanofluid over a 4-day period, confirming its consistency throughout the experiments. Moreover, the impact of heat load variation on the evaporator section was assessed using controlled heat inputs ranging from 10 to 80 W. Observations on the arrangement of slugs and plugs at a 50% filling ratio revealed interesting self-adjusting flow patterns in response to increasing heat inputs, providing valuable insights into PHP operational dynamics. Notably, the oscillatory flow behavior of Fe3O4/water, the chosen working fluid, exhibited greater activity in comparison to water. This distinctive flow behavior contributed to achieving heightened thermal performance efficiency for the Fe3O4/water system, attributed to its faster attainment of the annular flow condition.

Behind the Non-Uniform Breakup of Bubble Slug in Y-Shaped Microchannel: Dynamics and Mechanisms.

Bubble flow in confined geometries is a problem of fundamental and technological significance. Among all the forms, bubble breakup in bifurcated microchannels is one of the most commonly encountered scenarios, where an in-depth understanding is necessary for better leveraging the process. This study numerically investigates the non-uniform breakup of a bubble slug in Y-shaped microchannels under different flow ratios, Reynolds numbers, and initial bubble volumes. Overall, the bubble can either breakup or non-breakup when passing through the bifurcation and shows different forms depending on flow regimes. The flow ratio-Reynolds number phase diagrams indicate a power-law transition line of breakup and non-breakup. The bubble takes longer to break up with rising flow ratios yet breaks earlier with higher Reynolds numbers and volumes. Non-breakup takes less time than the breakup patterns. Flow ratio is the origin of non-uniform breakup. Both the Reynolds number and initial volume influence the bubble states when reaching the bifurcation and thus affect subsequent processes. Bubble neck dynamics are analyzed to describe the breakup further. The volume distribution after breaking up is found to have a quadratic relation with the flow ratio. Our study is hoped to provide insights for practical applications related to non-uniform bubble breakups.

Characterization of Gas-Liquid Two-Phase Slug Flow Using Distributed Acoustic Sensing in Horizontal Pipes.

This article discusses the use of distributed acoustic sensing (DAS) for monitoring gas-liquid two-phase slug flow in horizontal pipes, using standard telecommunication fiber optics connected to a DAS integrator for data acquisition. The experiments were performed in a 14 m long, 5 cm diameter transparent PVC pipe with a fiber cable helically wrapped around the pipe. Using mineral oil and compressed air, the system captured various flow rates and gas-oil ratios. New algorithms were developed to characterize slug flow using DAS data, including slug frequency, translational velocity, and the lengths of slug body, slug unit, and the liquid film region that had never been discussed previously. This study employed a high-speed camera next to the fiber cable sensing section for validation purposes and achieved a good correlation among the measurements under all conditions tested. Compared to traditional multiphase flow sensors, this technology is non-intrusive and offers continuous, real-time measurement across long distances and in harsh environments, such as subsurface or downhole conditions. It is cost-effective, particularly where multiple measurement points are required. Characterizing slug flow in real time is crucial to many industries that suffer slug-flow-related issues. This research demonstrated the DAS's potential to characterize slug flow quantitively. It will offer the industry a more optimal solution for facility design and operation and ensure safer operational practices.

Division of labor for defensive retaliation and preemption by the peripheral and central nervous systems in the nudibranch Berghia.

Relatively little is known about how peripheral nervous systems (PNSs) contribute to the patterning of behavior in which their role transcends the simple execution of central motor commands or mediation of reflexes. We sought to draw inferences to this end in the aeolid nudibranch Berghia stephanieae, which generates a rapid, dramatic defense behavior, "bristling." This behavior involves the coordinated movement of cerata, dozens of venomous appendages emerging from the animal's mantle. Our investigations revealed that bristling constitutes a stereotyped but non-reflexive two-stage behavior: an initial adduction of proximate cerata to sting the offending stimulus (stage 1) followed by a coordinated radial extension of remaining cerata to create a pincushion-like defensive screen around the animal (stage 2). In decerebrated specimens, stage 1 bristling was preserved, while stage 2 bristling was replaced by slower, uncoordinated ceratal movements. We conclude from these observations that, first, the animal's PNS and central nervous system (CNS) mediate stages 1 and 2 of bristling, respectively; second, the behavior propagates through the body utilizing both peripheral- and central-origin nerve networks that support different signaling kinetics; and third, the former network inhibits the latter in the body region being stimulated. These findings extend our understanding of the PNS' computational capacity and provide insight into a neuroethological scheme in which the CNS and PNS both independently and interactively pattern different aspects of non-reflexive behavior.

Immune-Related Gene Profiles and Differential Expression in the Grey Garden Slug Deroceras reticulatum Infected with the Parasitic Nematode Phasmarhabditis hermaphrodita.

The grey garden slug (Deroceras reticulatum), a common terrestrial slug native to Europe with a global distribution including North America, is commonly considered the most severe slug pest in agriculture. The nematode Phasmarhabditis hermaphrodita, which has been used in the U.K. and Europe as a commercial biocontrol agent since 1994, has also recently been collected in Oregon and California and has long been considered a candidate biocontrol agent for slug management in the U.S. In this study, we report differential gene expressions in nematode-infected slugs using RNA-seq to identify slug immune-related genes against nematodes. Comparison of gene expression levels between the whole bodies of a nematode-infected slug (N-S) and an uninfected control slug (C-S) revealed that there were a total of 39,380 regulated unigenes, of which 3084 (3%) were upregulated and 6761 (6%) were downregulated at greater than 2-fold change (FC > 2) in the nematode-infected slug. To further investigate the biological functions of differentially expressed genes (DEGs), gene ontology (GO) and functional enrichment analysis were performed to map the DEGs to terms in the GO, eukaryotic ortholog groups of proteins (KOG) and Kyoto Encyclopedia of Genes and Genome Pathway (KEGG) databases. Among these DEGs, approximately 228 genes associated with immunity or immune-related pathways were upregulated 2-fold or more in the N-S compared to C-S. These genes include toll, Imd, JNK, scavenger receptors (SCRs), C-type lectins (CTLs), immunoglobulin-like domains, and JAK/STAT63 signaling pathways. From the RNA-seq results, we selected 18 genes and confirmed their expression levels by qRT-PCR. Our findings provide insights into the immune response of slugs during nematode infection. These studies provide fundamental information that will be valuable for the development of new methods of pest slug control using pathogenic nematodes in the field.

A Novel Interaction of Slug (SNAI2) and Nuclear Actin.

Actin is a protein of central importance to many cellular functions. Its localization and activity are regulated by interactions with a high number of actin-binding proteins. In a yeast two-hybrid (Y2H) screening system, snail family transcriptional repressor 2 (SNAI2 or slug) was identified as a yet unknown potential actin-binding protein. We validated this interaction using immunoprecipitation and analyzed the functional relation between slug and actin. Since both proteins have been reported to be involved in DNA double-strand break (DSB) repair, we focused on their interaction during this process after treatment with doxorubicin or UV irradiation. Confocal microscopy elicits that the overexpression of actin fused to an NLS stabilizes complexes of slug and γH2AX, an early marker of DNA damage repair.

Effects of Resveratrol on In Vivo Ovarian Cancer Cells Implanted on the Chorioallantoic Membrane (CAM) of a Chicken Embryo Model.

Ovarian cancer poses a significant threat to patients in its advanced stages, often with limited treatment options available. In such cases, palliative management becomes the primary approach to maintaining a reasonable quality of life. Therefore, the administration of any medication that can benefit patients without a curative option holds potential. Resveratrol, a natural compound known for its in vitro anticancer activities, has generated contrasting results in vivo and human studies. In this study, we aimed to assess the anticancer effects of resveratrol on ovarian cancer cells grown on the chorioallantoic membrane (CAM) of chicken embryos. Two ovarian cancer cell lines, OVCAR-8 and SKOV-3, were cultured in collagen scaffolds for four days before being implanted on the CAM of chicken embryos on day 7. Different doses of resveratrol were applied to the CAM every two days for six days. Subsequently, CAM tissues were excised, fixed, and subjected to histological analysis. Some CAM tumours were extracted to analyse proteins through Western blotting. Our findings indicate that specific doses of resveratrol significantly reduce angiogenic activities, pNF-κB levels, and SLUG protein levels by using immunohistochemistry. These results suggest that resveratrol may have the potential to impact the behaviour of ovarian cancer CAM tumours, thereby warranting further consideration as a complementary treatment option for women with incurable ovarian cancer.

Neural and Neural Crest-Derived Stem Cell Distribution in the Adult Human Dental Pulp

SUMMARY: Despite comprehensive studies and reports about the properties of dental pulp stem cells (DPSCs) in vitro, we still need to confirm whether these in vitro characteristics coincide with the nature of DPSCs in situ. The anatomical location of DPSCs populations in the dental pulp has yet to be investigated. Moreover, the mesenchymal DPSCs have been much more studied than the neural crest-derived DPSCs. In this study, well-recognized neural/neural crest stem cell markers NCAM1, Nestin, SNAIL/SLUG, SOX9, and S100 are being investigated by immunohistochemistry to localize the precise location of these populations of DPSCs within the human adult dental pulp.All previously mentioned markers were expressed in the dental pulp, and their intensity and location of expression were reported.

A pesar de estudios e informes exhaustivos sobre las propiedades de las células madre de la pulpa dental (DPSC) in vitro, todavía necesitamos confirmar si estas características in vitro coinciden con la naturaleza de las DPSC in situ. La ubicación anatómica de las poblaciones de DPSC en la pulpa dental aún no se ha investigado. Además, las DPSC mesenquimales han sido mucho más estudiadas que las DPSC derivadas de la cresta neural. En este estudio, se están investigando mediante inmunohisto química marcadores de células madre de la cresta neural/ neural NCAM1, Nestin, SNAIL/SLUG, SOX9 y S100 para localizar la ubicación precisa de estas poblaciones de DPSC dentro de la pulpa dental humana adulta. Todos los marcadores mencionados anteriormente se expresaron en la pulpa dental y se informó su intensidad y ubicación de expresión.

P4HA2 involved in SLUG-associated EMT predicts poor prognosis of patients with KRAS-positive colorectal cancer.

This study aimed to examine the immunohistochemical expression of epithelial-mesenchymal transition biomarkers: P4HA2 and SLUG in colorectal carcinoma (CRC) specimens, then to assess their relation to clinicopathological features including KRAS mutations and patients' survival, and finally to study the correlation between them in CRC. The result of this study showed that SLUG and P4HA2 were significantly higher in association with adverse prognostic factors: presence of lympho-vascular invasion, perineural invasion, higher tumor budding, tumor stage, presence of lymph node metastasis, and presence of distant metastasis. CRC specimens with KRAS mutation were associated with significant higher SLUG and P4HA2 expression. High expression of both SLUG and P4HA2 was significantly unfavorable prognostic indicator as regards overall survival (OS) and disease-free survival (DFS). In KRAS mutated cases, high P4HA2 expression was the only significant poor prognostic indicator as regarding DFS. In conclusions, our data highlight that both SLUG and P4HA2 expression may serve as potentially important poor prognostic biomarkers in CRC and targeting these molecules may be providing a novel therapeutic strategy. In KRAS mutation group, high P4HA2 expression is the only independent prognostic factor for tumor recurrence, so it can be suggested to be a novel target for therapy.

Preliminary Study on Hourly Dynamics of a Ground-Dwelling Invertebrate Community in a Farmland Vineyard.

We evaluated the hourly dynamics of ground-dwelling invertebrate communities in farmland using infrared camera traps between August and September 2022. No significant variations within 24 h nor between any two time points of each day were observed in the taxonomic richness and abundance of the entire community. However, the periods from 4:00 to 7:00 and 13:00 to 20:00 showed relatively high taxonomic richness, while those from 2:00 to 6:00 and 16:00 to 21:00 showed relatively high abundance. Millipede abundance varied significantly in a 24 h period, with higher abundance from 3:00 to 4:00 and 1:00 to 2:00. Additionally, slug, beetle, and grasshopper abundances were significantly higher from 22:00 to 23:00, 17:00 to 18:00, and 23:00 to 24:00, respectively. The abundance of other taxa did not show significant variations between any two time points of a day. Predominant generalist predators showed positive correlation in their activity times. These results suggest that significant variations within each 24 h period are uncommon at either community or taxa (except for millipedes) levels in farmland ground-dwelling invertebrates. Further, while most taxa had significantly preferred active hours, the total community did not. Therefore, hourly dynamics should be considered to understand biodiversity maintenance.

Optimizing slug bubble size for application of the ultra-thin flat sheet membranes in MBR: a comprehensive study combining CFD simulation and experiment.

Optimizing the slug bubble size specifically for ultra-thin flat sheet membranes in MBR systems can effectively enhance the scouring force and improve fouling control efficiency, thereby further advancing their targeted and widespread application. In this study, a three-dimensional model was developed based on the practical application to investigate the impact of slug bubbles on scouring performance in ultra-thin flat sheet MBR systems, encompassing their evolution, disturbance level, and shear stress. A membrane fouling probability index for quantifying the distribution of membrane fouling, along with a turbulence intensity index have been proposed. The findings revealed that the 20-mL slug bubble induced the highest disturbance level in the surrounding fluid, characterized by an instantaneous peak velocity of 0.63 m/s at the local system level, conducive to bubble scouring. And exerted the greatest shear stress effect, achieving the most effective reduction in membrane contamination, with a maximum shear stress of 1.82 Pa. The experimental validation conducted during the operational cycles confirmed that the scouring effect of 20-mL slug flow yielded in a maximum proportion of 48.16% within the low fouling probability region. The results provided evidence supporting the assertion that specific aeration conditions producing 20 mL of bubbles resulted in minimal membrane fouling, ensuring a more pronounced scouring effect. The combination anythsis of slug bubble characteristics and behaviors, integrating theoretical and experimental approaches, implied that 20 mL was the optimal bubble size in ultra-thin flat sheet MBR, which fulfilled the optimal air scouring effect.

Plant volatiles mediated the orientation preference of slugs to different plant species.

BACKGROUND: Slugs mechanically damage plant leaves, resulting in significant economic losses. However, there are limited cost-efficient strategies available in slug management. By studying how slugs utilize plant volatiles to locate host plants, we can gain insights into the design of attractants and repellents. RESULTS: Bioassay results suggest slugs (Agriolimax agrestis) prefer to orientate to lettuce (Lactuca sativa), cabbage (Brassica oleracea L.), and young tobacco seedlings, compared with old tobacco seedlings. We analyzed the volatomics of lettuce, cabbage, young and old tobacco seedlings. 2-(2-butoxyethoxy)-ethanol acetate (2EA) had high abundance while nonanal, decanal, and ß-cylocitral had relatively low content in volatiles. Old tobacco seedlings released significantly more hexanal but fewer 1,4-dihydro-4-oxopyridazine (DO). In olfactory tests, hexanal, nonanal, decanal, and ß-cylocitral showed strong repellency to slugs, while DO at a dose of 500 ng/µL and 2EA at a dose of 1% were attractive to slugs. The two alkanes, hexadecane and heptadecane, had no effect on slug orientating to host plants. DO and 2EA can thus alleviate the repellency of hexanal, nonanal, decanal and ß-cylocitral. CONCLUSION: The high emission of hexanal in old tobacco seedlings helps repel slugs, while 2EA and DO attract slugs to lettuce and cabbage. These findings suggest that these chemicals can be utilized in the design of repellents and attractants, and contribute to constructing a push-pull system for slug control. © 2023 Society of Chemical Industry.

GMI, a Ganoderma microsporum protein, abolishes focal adhesion network to reduce cell migration and metastasis of lung cancer.

BACKGROUND: Cancer metastasis is a major cause of cancer-related deaths, emphasizing the urgent need for effective therapies. Although it has been shown that GMI, a fungal protein from Ganoderma microsporum, could suppress primary tumor growth in a wide spectrum of cancer types, it is still unclear whether GMI exhibits anti-metastasis properties, particularly in lung cancers. Further investigation is needed. AIMS AND OBJECTIVES: The objective of this study is to investigate the potential inhibitory effects of GMI on lung cancer metastasis in vivo. Utilizing systematic and comprehensive approaches, our research aims to elucidate the underlying molecular mechanisms responsible for the anti-metastatic effects. MATERIALS AND METHODS: In vitro migration and cell adhesion assays addressed the epithelial-to-mesenchymal transition (EMT)-related phenotype. Proteomic and bioinformatic analyses identified the GMI-regulated proteins and cellular responses. GMI-treated LLC1-bearing mice were analyzed using IVIS Spectrum to assess the anti-metastatic effect. KEY FINDINGS: GMI inhibits EMT as well as cell migration. GMI disrupts cell adhesion and downregulates integrin, resulting in inhibition of phosphorylated FAK. GMI induces macropinocytosis and lysosome-mediated degradation of integrin αv, α5, α6 and ß1. GMI downregulates Slug via inhibition of FAK activity, which in turn enhances expressions of epithelial-related markers and decreases cell mobility. Mechanistically, GMI-induced FAK inhibition engenders MDM2 expression and enhances MDM2/p21/Slug complex formation, leading to Slug degradation. GMI treatment reduces the metastatic pulmonary lesion and prolongs the survival of LLC1-bearing mice. SIGNIFICANCE: Our findings highlight GMI as a promising therapeutic candidate for metastatic lung cancers, offering potential avenues for further research and drug development.

NUAK1 promotes tumor metastasis through upregulating slug transcription in esophageal squamous cell carcinoma.

BACKGROUND: Metastasis is still a major cause of poor pathological outcome and prognosis in esophageal squamous cell carcinoma (ESCC) patients. NUAK1 has been reported highly expressed in many human cancers and is associated with the poor prognosis of cancer patients. However, the role of NUAK1 and its underlying signaling mechanism in ESCC metastasis remain unclear. METHODS: Expression of NUAK1 in ESCC was detected by real-time quantitative RT-PCR (qRT-PCR), Western blotting and immunohistochemical staining. MTT, colony formation, wound-healing and transwell assays were used to determine the role NUAK1 in vitro. Metastasis was evaluated by use of an experimental pulmonary metastasis model in BALB/c-nu/nu mice. The mechanisms were assessed by using coimmunoprecipitation, immunofluorescence and dual-luciferase reporter gene experiments. RESULTS: NUAK1 was highly expressed in ESCC tissues compared with the adjacent normal esophageal epithelial tissues. Moreover, the elevated expression of NUAK1 positively correlated with tumor invasion depth, lymph node metastasis, pathological TNM stage, and poor survival in ESCC patients. Further experiments showed that NUAK1 overexpression did not change the cell viability and colony formation of ESCC cells, while remarkably promoted the migration and invasion in vitro and experimental pulmonary metastasis in vivo. Mechanistically, NUAK1 enhanced the transcription level of Slug, which enhanced the migratory and invasive capability of ESCC cells. Consistently, silencing Slug almost completely diminished the migration and invasion of NUAK1-overexpressing ESCC cells. Further studies demonstrated that NUAK1 upregulated the transcription activity of Slug through activating the JNK/c-Jun pathway. CONCLUSION: These results demonstrated that NUAK1 promoted the metastasis of ESCC cells through activating JNK/c-Jun/Slug signaling, indicating NUAK1 is a promising therapeutic target for metastatic ESCC.

Hypoxia Affects Mitochondrial Stress and Facilitates Tumor Metastasis of Colorectal Cancer Through Slug SUMOylation.

BACKGROUND: Colorectal cancer (CRC) is a malignant tumor. Slug has been found to display a key role in diversified cancers, but its relevant regulatory mechanisms in CRC development are not fully explored. OBJECTIVE: Hence, exploring the function and regulatory mechanisms of Slug is critical for the treatment of CRC. METHODS: Protein expressions of Slug, N-cadherin, E-cadherin, Snail, HIF-1α, SUMO1, Drp1, Opa1, Mfn1/2, PGC-1α, NRF1, and TFAM were measured through western blot. To evaluate the protein expression of Slug and SUMO-1, an immunofluorescence assay was used. Cell migration ability was tested through transwell assay. The SUMOylation of Slug was examined through CO-IP assay. RESULTS: Slug displayed higher expression and facilitated tumor metastasis in CRC. In addition, hypoxia treatment was discovered to upregulate HIF-1α, Slug, and SUMO-1 levels, as well as induce Slug SUMOylation. Slug SUMOylation markedly affected mitochondrial biosynthesis, fusion, and mitogen-related protein expression levels to trigger mitochondrial stress. Additionally, the induced mitochondrial stress by hypoxia could be rescued by Slug inhibition and TAK-981 treatment. CONCLUSION: Our study expounded that hypoxia affects mitochondrial stress and facilitates tumor metastasis of CRC through Slug SUMOylation.

Biological activities of gastropods secretions: snail and slug slime.

Gastropods, a mollusk class including slugs and snails, represent an extraordinarily diverse and ecologically significant group of organisms featuring the largest class of invertebrates. They can be classified as aquatic and terrestrial animals having coiled shells, although some species have reduced or absent shells. Their unique body structure includes a muscular foot for locomotion, a visceral mass containing essential organs, and a distinct head region with sensory organs such as tentacles and eyes. They are used to secrete a complex mixture of glycoproteins, enzymes, peptides, mucus and other bioactive compounds, namely slime, which represents a tool to allow locomotion, protection, and interaction within different habitats. The biological activities of the slime have attracted considerable interest due to their diverse and potentially valuable properties ranging from defense mechanisms to potential therapeutic applications in wound healing, antimicrobial therapy, management of inflammation, and neurological disorders. This review aims at exploring the beneficial effects of snail and slug slime focusing, in particular, on the improvement of the biological processes underlying them. Continued exploration of the intricate components of these slimy secretions promises to discover new bioactive molecules with diverse applications in various scientific and industrial fields.

Peruvian nudibranchs (Mollusca, Gastropoda, Heterobranchia): an updated literature review-based list of species.

Nudibranchs, as a group, have received limited attention in terms of scientific study along the coastline of Peru. Here, an updated and comprehensive list of nudibranch species found in the Peruvian sea is presented, compiled through an extensive review of relevant literature. This compilation encompasses a total of 31 species, classified into two suborders, 10 superfamilies, 20 families, and 28 genera. With respect to the biogeographic provinces along the Peruvian coast, 23 species inhabit the Warm Temperate Southeastern Pacific province, 18 species occur in the Tropical Eastern Pacific province, and 10 species are found in both provinces, crossing the transitional zone between them. In terms of distribution patterns, two species exhibit a cosmopolitan distribution (Glaucusatlanticus and Fionapinnata), while two species display a circumtropical distribution (Cephalopygetrematoides and Phylliroebucephala). One species exhibits a bipolar distribution in the Eastern Pacific and possesses an amphi-South American distribution (Rostangapulchra). Additionally, six species exhibit an amphi-South American distribution (Rostangapulchra, Diaululapunctuolata, Dotouva, Tyrinnaevelinae, Tyrinnadelicata, and Dorisfontainii), and two species are endemic to Peru (Corambemancorensis and Felimaresechurana). This study provides comprehensive information on biogeographical aspects, geographical distributions, and taxonomic updates within the nudibranch species documented in Peru. Furthermore, we discuss the status of species listed in previous literature that have not been confirmed by collections, referring to them as potentially occurring species.

Gastropod Mucus: Interdisciplinary Perspectives on Biological Activities, Applications, and Strategic Priorities.

Terrestrial gastropod mucus exhibits multifunctional attributes, enabling diverse applications. This comprehensive review integrates insights across biomedicine, biotechnology, and intellectual property to elucidate the bioactivities, physicochemical properties, and ecological roles of snail and slug mucus. Following an overview of mucus functional roles in gastropods, promising applications are highlighted in wound healing, antimicrobials, biomaterials, and cosmetics, alongside key challenges. An analysis of global patent trends reveals surging innovation efforts to leverage gastropod mucus. Strategic priorities include bioprospecting natural diversity, optimizing stabilization systems, recombinant biosynthesis, and fostering collaboration to translate promising potentials sustainably into impactful technologies. Ultimately, harnessing the remarkable multifunctionality of gastropod mucus holds immense opportunities for transformative innovations in biomedicine, biotechnology, and beyond.

microRNA-203 inhibits migration and invasion of canine tonsillar squamous cell carcinoma cells by targeting SLUG.

Objective: Squamous cell carcinoma (SCC) occurring in the tonsils (TSCC) has a poorer prognosis than SCC occurring in other regions of the oral cavity (non-tonsillar SCC [NTSCC]) because it easily metastasizes to distant organs. This study aimed to elucidate the molecular mechanisms underlying the migration and invasion of TSCC cells in vitro. Materials and methods: This study focused on differential microRNA (miRNA) expression using microRNA microarrays and quantitative polymerase chain reaction in canine TSCC and NTSCC tissues and cell lines. A target gene of the miRNA involved in cell migration and invasion was validated by wound healing, transwell, and luciferase assays. Results: miR-203 expression was lower in TSCC tissues than in the normal oral mucosa and NTSCC tissues. Transfection of the miR-203 mimic resulted in the downregulation of mesenchymal marker protein expression and attenuation of cell migration and invasion in TSCC cells, but not in NTSCC cells. A dual-luciferase assay revealed that miR-203 directly targeted the mesenchymal transcription factor SLUG. SLUG overexpression enhances the migration of TSCC cells. Conclusion: Our study indicates that the miR-203/SLUG axis may be involved in the metastatic mechanisms of TSCC.

ETV5 facilitates tumor progression in head-neck squamous cell carcinoma.

OBJECTIVE: E26 transformation-specific (ETS) factors have emerged as key mediators underlying human tumorigenesis. Here, we sought to characterize the expression pattern, biological roles, and clinical significance of ETS Variant Transcription Factor 5 (ETV5) in head neck squamous cell carcinoma (HNSCC). SUBJECTS AND METHODS: ETV5 expression pattern in HNSCC was determined by bioinformatics interrogations and immunohistochemical staining in primary samples. The associations between its abundance with clinicopathological parameters, and patient survival were evaluated. Colony formation, CCK-8, flow cytometry, wound healing, and Transwell invasion assays, as well as xenograft models, were utilized to determine the phenotypic changes after ETV5 silencing in vitro and vivo. The potential binding of ETV5 in the Slug promoter was determined by ChIP-qPCR. RESULTS: ETV5 was significantly overexpressed in HNSCC samples. Its overexpression is significantly associated with aggressiveness features and reduced survival. ETV5 knockdown significantly inhibited cell proliferation, migration, invasion, and induced apoptosis in vitro, and impaired tumor growth in vivo. Moreover, ETV5-activated Slug transcription by binding its promoter region in HNSCC cells. Patients with ETV5high Slughigh had the worst survival across multiple HNSCC cohorts. CONCLUSIONS: Our findings reveal that ETV5 serves as a novel prognostic biomarker and putative oncogene for HNSCC progression likely by activating Slug transcription.