Inhibition of phosphatidylinositol 3-kinase catalytic subunit alpha by miR-203a-3p reduces hypertrophic scar formation via phosphatidylinositol 3-kinase/AKT/mTOR signaling pathway.

Background: Hypertrophic scar (HS) is a common fibroproliferative skin disease that currently has no truly effective therapy. Given the importance of phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) in hypertrophic scar formation, the development of therapeutic strategies for endogenous inhibitors against PIK3CA is of great interest. Here, we explored the molecular mechanisms underlying the protective effects of miR-203a-3p (PIK3CA inhibitor) against excessive scar. Methods: Bioinformatic analysis, immunohistochemistry, immunofluorescence, miRNA screening and fluorescence in situ hybridization assays were used to identify the possible pathways and target molecules mediating HS formation. A series of in vitro and in vivo experiments were used to clarify the role of PIK3CA and miR-203a-3p in HS. Mechanistically, transcriptomic sequencing, immunoblotting, dual-luciferase assay and rescue experiments were executed. Results: Herein, we found that PIK3CA and the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway were upregulated in scar tissues and positively correlated with fibrosis. We then identified miR-203a-3p as the most suitable endogenous inhibitor of PIK3CA. miR-203a-3p suppressed the proliferation, migration, collagen synthesis and contractility as well as the transdifferentiation of fibroblasts into myofibroblasts in vitro, and improved the morphology and histology of scars in vivo. Mechanistically, miR-203a-3p attenuated fibrosis by inactivating the PI3K/AKT/mTOR pathway by directly targeting PIK3CA. Conclusions: PIK3CA and the PI3K/AKT/mTOR pathway are actively involved in scar fibrosis and miR-203a-3p might serve as a potential strategy for hypertrophic scar therapy through targeting PIK3CA and inactivating the PI3K/AKT/mTOR pathway.

Biological carbon pump estimate based on multidecadal hydrographic data.

The transfer of photosynthetically produced organic carbon from surface to mesopelagic waters draws carbon dioxide from the atmosphere1. However, current observation-based estimates disagree on the strength of this biological carbon pump (BCP)2. Earth system models (ESMs) also exhibit a large spread of BCP estimates, indicating limited representations of the known carbon export pathways3. Here we use several decades of hydrographic observations to produce a top-down estimate of the strength of the BCP with an inverse biogeochemical model that implicitly accounts for all known export pathways. Our estimate of total organic carbon (TOC) export at 73.4 m (model euphotic zone depth) is 15.00 ± 1.12 Pg C year-1, with only two-thirds reaching 100 m depth owing to rapid remineralization of organic matter in the upper water column. Partitioned by sequestration time below the euphotic zone, τ, the globally integrated organic carbon production rate with τ > 3 months is 11.09 ± 1.02 Pg C year-1, dropping to 8.25 ± 0.30 Pg C year-1 for τ > 1 year, with 81% contributed by the non-advective-diffusive vertical flux owing to sinking particles and vertically migrating zooplankton. Nevertheless, export of organic carbon by mixing and other fluid transport of dissolved matter and suspended particles remains regionally important for meeting the respiratory carbon demand. Furthermore, the temperature dependence of the sequestration efficiency inferred from our inversion suggests that future global warming may intensify the recycling of organic matter in the upper ocean, potentially weakening the BCP.

Expression of PTP4A1 in circulating tumor cells and its efficacy evaluation in patients with early- and intermediate-stage esophageal cancer.

The objective of this study is to investigate the expression of protein tyrosine phosphatase type I (PTP4A1) in circulating tumor cells (CTCs) in patients with early- and intermediate-stage esophageal cancer and its clinical value in evaluating patient prognosis. Tissue and peripheral blood samples were collected from patients with esophageal cancer, as well as their clinical data. Follow-up was performed on all patients. PTP4A1 expression in the CTCs of patients were analyzed by regression analysis, and its correlation with the clinical characteristics of esophageal cancer was discussed. The numbers of mixed tumor cells and T-CTCs were significantly correlated with lymph node metastasis. Advanced tumor-node metastasis (TNM) stage (odds ratio = 12.063) and lymph node metastasis (odds ratio = 13.541) were influencing factors of PTP4A1+MCTC expression disorders in patients with esophageal cancer. The receiver operating characteristic curve showed that TNM stage and lymph node metastasis had a high predictive efficiency for PTP4A1+MCTCs, with an area under the ROC curve of 0.725. PTP4A1+mixed tumor cells had strong predictive value for the efficacy of neoadjuvant therapy, with a sensitivity of 94.7% and a specificity of 63.6%. Advanced TNM stage and lymph node metastasis are influencing factors for increased CTCs and poor expression of PTP4A1 in patients with esophageal cancer.

Quantitative biochemical phenotypic heterogeneity of senescent macrophage at a single cell level by Synchrotron Radiation Fourier Transform Infrared Microspectroscopy.

Macrophage senescence plays an important role in pathophysiological process of age-related diseases such as atherosclerosis, chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, and lung cancer. After macrophage senescence, the biochemical phenotypes related to biological functions showed great heterogeneity. However, the biochemical phenotype and phenotypic heterogeneity of senescent macrophage has not been fully understood. Exploring the phenotype of biochemical substances in senescent macrophage will be helpful for understanding the function of senescent macrophage and finding out the potential mechanism between immune macrophage senescence and age-related diseases. In this study, we employed SR-FTIR microspectroscopy to detect the biochemical phenotype and phenotypic heterogeneity of single macrophage. The whole infrared spectra of senescent macrophages shifted, indicating biochemical substance changes within senescent macrophages. PCA and intercellular Euclidean distance statistical analysis based on specific spectra regions revealed dynamic changes of lipids and proteins during macrophage senescence. This proved that SR-FTIR microspectroscopy is an effective tool to detect the single cell biochemical phenotype transformation and phenotypic heterogeneity during macrophage senescence. It is of great significance to provide an evaluation method or clue for the study of cellular functions related to intracellular biochemical substances.

Permeability decides the effect of antibiotics on sedimentary nitrogen removal in Jiulong River Estuary.

Sedimentary denitrification takes place beneath the oxic layer at the sediment-water interface, where nitrate and antibiotics need to diffuse through the overlying water. However, the antibiotics' effect on sedimentary N removal and associated N2O production has not been adequately investigated under in situ conditions. Here, isotope pairing techniques, including slurry incubations (potential) and intact core incubations (in situ), combined with metagenomic analysis were applied to investigate the impacts of two protein-inhibiting antibiotics (oxytetracycline and thiamphenicol) on sediment nitrogen removal in a subtropical estuary. Slurry incubations showed that the two antibiotics significantly inhibited denitrification (67-98%) and anammox (49-99%), while intact core incubations presented no antibiotic effect at upstream but significant inhibition (23%-52%) at downstream. Meanwhile, N2O yields were stimulated up to 20 folds in slurry incubations yet showing insignificant response in intact cores. Such contrasting results between up- and down-stream and between slurry and intact core incubations strongly indicated that permeability, which determines diffusion of antibiotics to microbes, is the key to exert the effect of antibiotics on in situ sedimentary nitrogen removal processes regardless the existence of antibiotics resistance genes. This diffusive obstruction may mitigate the toxic effect of antibiotics on nitrogen removal related microbes in natural environments.

Transition of source/sink processes and fate of ammonium in groundwater along with redox gradients.

Ammonium (NH4+) retention/removal processes in groundwater are of great interest because of the continuous increase in nitrogenous compound loading due to anthropogenic activities. However, the transition of multiple co-occurring transformation processes that determine the fate of NH4+ in groundwater along a redox gradient remains underexplored. We selected a high nitrogen (N) groundwater system in the western Hetao Basin, China, to identify and quantify NH4+ source and sink processes, including mineralization, dissimilatory nitrate reduction to ammonium (DNRA), nitrification, and anammox, to better understand the dynamics of NH4+. Based on redox-sensitive parameters, that is, the oxidation-reduction potential (ORP) and NH4+ and nitrate (NO3-) contents, etc., the groundwater system was classified into three zones from upstream to downstream: zone I (oxidizing), zone II (moderately reducing), and zone III (strongly reducing). Using the 15N tracing technique, we found that NH4+ was mainly produced by mineralization while < 2% was produced by DNRA throughout the study area. Mineralization increased downstream because the supply of biodegradable N-containing compounds was augmented, which created a strong redox gradient to host a serial reaction chain. In zone I, NH4+ was mainly transferred to NO3- via nitrification, whereas in zones II and III, NH4+ was mainly transferred to N2 via anammox. The average NH4+ production/consumption ratios (P/C) in zones I, II, and III were 0.7, 6.9, and 51.1, respectively. Obviously, the NH4+ purification ability can only exceed the supply under aerobic conditions, thus suggesting that NH4+ will accumulate without limitation and be retained in strongly reducing groundwater. The situation of NH4+ accumulation would deteriorate over space and time in groundwater as human activities increase without an additional artificial supply of oxidants. The results provide mechanistic insights for quantitatively comprehending the dynamics and fate of NH4+ in groundwater, shedding light on groundwater NH4+ mitigation techniques.

Integration of single-cell and bulk transcriptomics reveals immune-related signatures in keloid.

BACKGROUND: Keloid is a pathological dermatological condition that manifests as an overgrowth scar secondary to skin trauma. This study endeavored to excavate immune-related signatures of keloid based on single-cell RNA (scRNA) sequencing data and bulk RNA sequencing data. METHOD: The keloid-relevant scRNA sequencing dataset GSE163973 and bulk RNA sequencing dataset GSE113619 were mined from the GEO database. The "Seurat" R package was utilized for data quality control, cell clustering, and investigation of marker genes of each cell cluster. The "SingleR" package helped match the marker genes of the corresponding cluster to specific cell types. Moreover, the R package "Monocle" was deployed for pseudotemporal ordering analysis, and the "clusterProfiler" was applied for functional and pathway enrichment analysis. The immune-related signatures were then identified, and potential targeted drugs were predicted via the DGIdb database. Verification of the immune-related signatures in clinical validation samples was implemented by RT-qPCR. RESULTS: Totally 23 cell clusters were screened and classified into 10 cell types based on the scRNA sequencing data. The keloid group had a significantly higher endothelial cell proportion than the control group. As enrichment analysis was applied in both differentially expressed genes (DEGs) of scRNA and bulk RNA sequencing data, we found they were enriched in multiple common immune-related pathways and biological processes. Meanwhile, we acquired three immune-related signatures (VCAM1, CALCRL, and HLA-DPB1) by intersecting the above DEGs with immune-related genes (IRGs). Then, we predicted 16 drugs potentially targeting the biomarkers through the DGIdb database. Finally, the outcome of RT-qPCR of clinical validation samples further verified the results. CONCLUSION: In conclusion, we analyzed the cell types and functional differences in the keloid through scRNA and bulk RNA sequencing data. We identified three immune-related signatures (VCAM1, CALCRL, and HLA-DPB1) in keloid, providing a basis for further in-depth investigation of the molecular mechanisms of keloid and exploration of therapeutic targets.

Long noncoding RNA LIPH-4 promotes esophageal squamous cell carcinoma progression by regulating the miR-216b/IGF2BP2 axis.

INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) represents a major malignancy with poor clinical outcomes. Long noncoding RNAs (lncRNAs) are known to regulate the development and progression of multiple cancers. However, how lncRNAs are involved in ESCC is currently undefined. METHODS: LIPH-4 levels in ESCC tissue specimens and cells were assessed by qRT-PCR. The biological function of LIPH-4 was examined in cell and animal studies, applying CCK-8, EdU, colony formation and flow cytometry assays as well as xenograft model experiments. The underlying mechanisms of action of LIPH-4 were explored through bioinformatics, luciferase reporter assay, RNA-immunoprecipitation assay and immunoblot. RESULTS: We identified a novel lncRNA, LIPH-4, which showed elevated amounts in ESCC tissues and positive correlations with increased tumor size and poor prognosis in ESCC patients. Functional studies showed that LIPH-4 promoted the growth, mediated cell cycle progression and inhibited apoptosis in ESCC cells in vitro, and promoted tumor growth in mice. In terms of mechanism, LIPH-4 could bind to miR-216b and act as a competing endogenous RNA (ceRNA) to induce the expression of miR-216's target gene IGF2BP2. LIPH-4 played an oncogenic role in ESCC through the miR-216b/IGF2BP2 axis. CONCLUSIONS: This study suggested that LIPH-4 functions as a novel oncogenic lncRNA by acting as a ceRNA for miR-216b to regulate IGF2BP2, indicating LIPH-4 likely constitutes a prognostic biomarker and therapeutic target in ESCC.

Diel change in inorganic nitrogenous nutrient dynamics and associated oxygen stoichiometry along the Pearl River Estuary.

The reactive nitrogen (N) emitted from continents significantly perturbs the pristine N cycle around the land-ocean boundary resulting in eutrophication and hypoxia. As nutrients are transported downstream through an estuary, various types of biological processes co-occur to modulate nitrogen speciation to influence the biogeochemical habitats for downstream microorganisms. We surveyed the Pearl River Estuary to examine the N transfer dynamics among nitrogen species with considering process-specific oxygen production and consumption. By using 15N pulse-tracing techniques, we measured ammonia oxidation and uptakes of ammonium, nitrite, and nitrate simultaneously under dark and light conditions in parallel. Light strongly inhibited nitrification but enhanced N uptake, and such light effect was further considered in the calculation for nitrogen transformation rates over a diel cycle. We found both oxidation and uptake of ammonium decreased seaward as substrate decreased. The nitrifier and phytoplankton work in antiphase to draw down incoming ammonium rapidly. Contrary to ammonium uptake, uptake of nitrite and nitrate showed a seaward increasing pattern. Such an inverse spatial pattern implies a shift in N preference for phytoplankton. Such high ammonium preference inhibits nitrate/nitrite uptake allowing them to behave conservatively in the estuary and to travel farther to outer estuary. By integrating oxygen consumption and production induced by N transformation processes over the diel cycle, oxygen was produced although allochthonous ammonium input is high (∼250 µM). For most stations, ammonium was completely consumed within 2 days, some stations even less than 0.5 days, implying that although the water residence time is short (2-15 days), tremendous input of ammonium N from upstream was transformed into particulate organic or nitrate forms during traveling to modulate the biogeochemical niche, including substrate, organics and oxygen, of coastal microbes in water column and sediments.

Oncogenic roles of the lncRNA LINC00460 in human cancers.

Long noncoding RNAs (lncRNAs) represent an important group of endogenous RNAs with limit protein-encoding capability, with a length of more than 200 nucleotides. Emerging evidence have demonstrated that lncRNAs are greatly involved in multiple cancers by playing critical roles in tumor initiation and progression. Long intergenic non-protein coding RNA 460 (LINC00460), a novel cancer-related lncRNA, exhibits abnormal expression and oncogenic function in multiple cancers, and positively correlates with poor clinical characteristics of cancer patients. LINC00460 has also been shown to be a promising biomarker for diagnosis as well as prognostic evaluation in cancer patients. In this review, we briefly summarized recent knowledge on the expression, functional roles, molecular mechanisms, and diagnostic and prognostic values of LINC00460 in human malignancies.

Perioperative Outcomes of Video-Assisted Thoracoscopic Surgery Versus Open Thoracotomy After Neoadjuvant Chemoimmunotherapy in Resectable NSCLC.

Background: Neoadjuvant chemoimmunotherapy becomes more widespread in the treatment of NSCLC, but few studies have reported the details of surgical techniques and perioperative challenges following neoadjuvant chemoimmunotherapy until now. The primary aim of our study was to address the feasibility and safety of pulmonary resection after neoadjuvant chemoimmunotherapy via different surgical approaches, video-assisted thoracoscopic surgery (VATS) and open thoracotomy. Methods: Patients with an initial diagnosis of clinical stage IB-IIIB(T3-4N2) NSCLC, who received neoadjuvant chemoimmunotherapy and surgery between January 2019 and August 2021 were included. Patients were retrospectively divided into two groups (VATS, and thoracotomy), and differences in perioperative, oncological, and survival outcomes were compared. Results: In total, there were 131 NSCLC patients included. Surgery was delayed beyond 42 days in 21 patients (16.0%), and radical resection (R0) was achieved in 125 cases (95.4%). Lobectomy was the principal method of pulmonary resection (102 cases, 77.9%) and pneumonectomy was performed in 11 cases (8.4%). Postoperative complications within 30 days occurred in 28 patients (21.4%), and no 90-day mortality was recorded. There were 53 patients (38.5%) treated with VATS, and 78 (59.5%) with open thoracotomy. VATS could achieve similar definitive resection rates, postoperative recovery courses, comparable morbidities, and equivalent RFS rates(p>0.05), with the advantages of reduced operative time (160.1 ± 40.4 vs 177.7 ± 57.7 min, p=0.042), less intraoperative blood loss (149.8 ± 57.9 vs 321.2 ± 72.3 ml, p=0.021), and fewer intensive care unit(ICU) stays after surgery (3.8% vs 20.5%, p=0.006) compared with open thoracotomy. However, the mean number of total lymph nodes resected was lower in the VATS group (19.5 ± 7.9 vs 23.0 ± 8.1, p=0.013). More patients in the thoracotomy group received bronchial sleeve resection/bronchoplasty (53.8% vs 32.1%, p=0.014) and vascular sleeve resection/angioplasty (23.1% vs 3.8%, p=0.003). After propensity score matching (PSM) analysis, VATS still had the advantage of fewer ICU stays after surgery (2.3% vs. 20.5%, p=0.007). Conclusions: Our results have confirmed that pulmonary resection following neoadjuvant PD-1 inhibitors plus chemotherapy is safe and feasible. VATS could achieve similar safety, definitive surgical resection, postoperative recovery, and equivalent oncological efficacy as open thoracotomy, with the advantage of fewer ICU stays after surgery.

Identification and validation of HOXD3 and UNC5C as molecular signatures in keloid based on weighted gene co-expression network analysis.

BACKGROUND: Keloid is a benign proliferative disease characterized by excessive deposition of extracellular matrix collagen during skin wound healing. The mechanisms of keloid formation have not been fully elucidated, and the current treatment methods are not effective for all keloid patients. Therefore, there is an urgent need to find more effective therapies, and our research focused on identifying characteristic molecular signatures of keloid to explore potential therapeutic targets. METHODS: Gene expression profiles of keloid and control group samples were retrieved from the GEO database. Taking the GSE113619 dataset as the training set, the dataset collected skin tissues from non-lesion sites of healthy and keloid-prone individuals, denoted as Day0. The second sampling was performed 42 days later at the original sampling site of control and keloid groups, denoted as Day42.The 'limma' package and Venn diagram identified differentially expressed genes (DEGs) specific to keloid day42 versus day0 samples. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome pathway functional enrichment, and annotation of the characteristic genes were conducted on the Metascape website. Ingenuity canonical pathways, disease & function enrichment analysis and gene interaction network were performed and predicted in Ingenuity Pathway Analysis (IPA) software. Key module genes related to keloid were filtered out by Weighted Gene Co-expression Network Analysis (WGCNA). We utilized the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm to screen the characteristic genes in keloid by the 'glmnet' package. The area under the curve (AUC) of receiver operating characteristic (ROC) was utilized to determine the effectiveness of potential signatures in discriminating keloid samples from normal samples and performed by using the 'pROC' package. The enrich scores of 24 immune cells in each sample were calculated by the single-sample gene set enrichment analysis (ssGSEA) algorithm， and then the Gene Set Variation Analysis (GSVA) was performed. Finally, RNA from 4 normal and 6 keloid samples was extracted, and RT-qPCR and Western Blot validated the expression of characteristic genes. RESULTS: A total of 640 DEGs specific to keloid day42 versus day0 samples were detected. 69 key module genes were uncovered and implicated in 'NCAM signaling for neurite out-growth', 'oncogenic MAPK signaling', 'transmission across chemical synapses' pathways, and the mitotic cell cycle-related processes. Five characteristic genes (MTUS1, UNC5C, CEP57, NAA35, and HOXD3) of keloid were identified by LASSO, and among which UNC5C and HOXD3 were validated by ROC plot in external dataset, RT-qPCR and Western Blot in validation samples. The result of ssGSEA indicated that the infiltration of neutrophils showed a relatively higher abundance and natural killer cells with relatively low enrichment in the keloid group compared to the control group. UNC5C was correlated with more immune cells compared with other characteristic genes. CONCLUSION: In this study, characteristic genes associated with keloid were identified by bioinformatic approaches and verified in clinical validation samples, providing potential targets for the diagnosis and treatment of keloid.

Physiological and metabolic effects of glyphosate as the sole P source on a cosmopolitan phytoplankter and biogeochemical implications.

Nutrient conditions influence the physiology and stoichiometry of marine phytoplankton. While extensive studies have documented the effects of abundances and types of nutrients such as nitrogen (N) and phosphorus (P), the effect of phosphonates as a P source is less understood and underexplored. Here, with the cosmopolitan coccolithophorid Emiliania huxleyi as a model phytoplankter, we investigated the effect of the phosphonate type of herbicide glyphosate as the sole P source in comparison with the P-depleted and P-replete (with 36 µM dissolved inorganic phosphate [DIP]) cultures. We measured changes in cellular C (carbon):P and N:P ratios and physiological performance and documented the corresponding transcriptomic and miRNAomic responses in E. huxleyi to glyphosate treatment. We found that glyphosate supported population growth but not to the full scale relative to DIP, and this was under the concerted regulation of DNA replication and cell cycle arrest genes as well as the growth-regulating miRNA. Furthermore, our data suggest that E. huxleyi took up glyphosate directly, bypassing extracellular hydrolysis, and this involved ABC transporters. Meanwhile, glyphosate-grown cultures displayed marked increases in cellular particulate organic C (POC) and PON contents, cell size, and transcription of genes for CO2 fixation and citrate cycle, nitrate transport, and protein biosynthesis. However, compared to DIP, the maximum absorption rate of glyphosate was only 33%, and glyphosate-grown E. huxleyi cells exhibited a mild P-stress symptom and elevated cellular C:P and N:P ratios. Interestingly, glyphosate-grown cells showed an increased sinking rate, suggesting that glyphosate as the sole P source might enhance the efficiency of C export by E. huxleyi, which would compensate for the expected decline in primary productivity (and hence carbon efflux) in the future more nutrient-depleted ocean. This biogeochemical implication needs to be further studied and verified, however.

LncRNA GACAT3 promotes esophageal squamous cell carcinoma progression through regulation of miR-149/FOXM1.

BACKGROUND: The long noncoding RNA gastric cancer associated transcript 3 (GACAT3) has been demonstrated to be implicated in the carcinogenesis and progression of many malignancies. However, GACAT3's levels and role in esophageal squamous cell carcinoma (ESCC) has not been elucidated. METHODS: GACAT3 amounts were investigated in ESCC tissues and cell lines by qPCR. Its biological functions were examined by CCK-8 assay, colony formation assay, flow cytometry, wound healing assay, transwell assay, and xenograft model establishment. The relationship between GACAT3 and miR-149 was assessed by dual-luciferase reporter assay. RESULTS: GACAT3 amounts were elevated in ESCC tissue and cell specimens. Functional studies showed that GACAT3 silencing reduced the proliferation, migration and invasion of cultured ESCC cells, and decreased tumor growth in mice. Furthermore, GACAT could directly interact with miR-149. In addition, colony formation and invasion assays verified that GACAT3 promotes ESCC tumor progression through miR-149. Moreover, GACAT3 acted as a competing endogenous RNA (ceRNA) to modulate FOXM1 expression. CONCLUSIONS: These findings indicate that GACAT3 functions as an oncogene by acting as a ceRNA for miR-149 to modulate FOXM1 expression in ESCC, suggesting that GACAT3 might constitute a therapeutic target in ESCC.

miR-21-5p/SMAD7 axis promotes the progress of lung cancer.

BACKGROUND: Lung cancer is one of the most common malignant tumors threatening human health. The aim of this study was to investigate the function of miR-21-5p in lung cancer progression. METHODS: We analyzed the expression levels of miR-21-5p in lung cancer tissues and cell lines. The qRT-PCR and MTT assays were performed after transfection with miR-21-5p mimic, inhibitor and negative control into lung cancer cells. RESULTS: Luciferase reporter assays showed miR-21-5p directly target SMAD7. The miR-21-5p inhibitor significantly suppressed lung cancer cell proliferation, invasion and migration. We found that SMAD7 was upregulated in lung cancer tissue. In addition, we found that SMAD7 inhibited lung cancer cell proliferation and miR-21-5p mimic damaged the inhibitory effect of SMAD7. CONCLUSIONS: miRNA-21-5p may promote cell proliferation, migration and invasion by spoiling SMAD7 expression in lung cancer cells.

LncRNA SNHG16 as a potential biomarker and therapeutic target in human cancers.

Long non-coding RNAs (lncRNAs) represent an important class of RNAs comprising more than 200 nucleotides, which are produced by RNA polymerase II. Although lacking an open reading framework and protein-encoding activity, lncRNAs can mediate endogenous gene expression by serving as chromatin remodeler, transcriptional or post-transcriptional modulator, and splicing regulator during gene modification. In recent years, increasing evidence shows the significance of lncRNAs in many malignancies, with vital roles in tumorigenesis and cancer progression. Moreover, lncRNAs were also considered potential diagnostic and prognostic markers in cancer. The lncRNA small nuclear RNA host gene 16 (SNHG16), found on chromosome 17q25.1, represents a novel tumor-associated lncRNA. SNHG16 was recently found to exhibit dysregulated expression in a variety of malignancies. There are growing evidence of SNHG16's involvement in characteristics of cancer, including proliferation, apoptosis, together with its involvement in chemoresistance. In addition, SNHG16 has been described as a promising diagnostic and prognostic biomarker in cancer patients. The current review briefly summarizes recently reported findings about SNHG16 and discuss its expression, roles, mechanisms, and diagnostic and prognostic values in human cancers.

Parthenolide Inhibits Angiogenesis in Esophageal Squamous Cell Carcinoma Through Suppression of VEGF.

BACKGROUND: Parthenolide (PT), the effective active ingredient of the medicinal plant, feverfew (Tanacetum parthenium), has been used as an anti-inflammatory drug due to its involvement in the inhibition of the NF-кB pathway. Moreover, recent studies have demonstrated the anti-tumor effect of PT in several cancers. However, the effect of PT on esophageal carcinoma remains unclear to date. In this study, we examined the inhibitory effects of PT and its underlying mechanism of action in human esophageal squamous cell carcinoma (ESCC) cells - Eca109 and KYSE-510. METHODS: The proliferation ability of Eca109 and KYSE-510 treated with PT was detected using the Cell Counting Kit-8 and colony forming assay. The Transwell assay and the wound healing assay were used to analyze the cell invasion and migration ability, respectively. The tube formation assay was used to investigate the effect of PT on tube formation of endothelial cells. The expression level of NF-кB, AP-1 and VEGF was analyzed by Western blot. RESULTS: We demonstrated that PT attenuates the proliferation and migration ability of ESCC cells in vitro and also inhibits tumor growth in the mouse xenograft model. In addition, PT exhibited anti-angiogenesis activity by weakening the proliferation, invasion and tube formation of endothelial cells in vitro and reduced microvessel density in the xenograft tumors. Further studies revealed that PT reduced the expression level of NF-кB, AP-1 and VEGF in ESCC cells. CONCLUSION: Collectively, the results of our study demonstrated that PT exerts anti-tumor and anti-angiogenesis effects possibly by inhibiting the NF-кB/AP-1/VEGF signaling pathway on esophageal carcinoma and might serve as a promising therapeutic agent for ESCC.

Author Correction: Genome-wide analyses of long non-coding RNA expression profiles and functional network analysis in esophageal squamous cell carcinoma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

SNHG7: A novel vital oncogenic lncRNA in human cancers.

Long noncoding RNAs (lncRNAs) are a group of RNAs that lack protein-coding ability, with lengths greater than 200 nucleotides. Increasing evidence has indicated that they mediate multiple physiological and pathological processes by regulating gene expression at the epigenetic, transcriptional, post-transcriptional, and translational levels. The deregulation of lncRNAs was demonstrated to have tumor suppressive or oncogenic effects, and thus, these molecules play vital regulatory roles in tumor initiation and progression. Small nucleolar RNA hostgene 7 (SNHG7) is a lncRNA located on chromosome 9q34.3. Different studies have explored the potential role of SNHG7 in the development and progression of multiple human malignancies such as bladder, breast, colorectal, esophageal, gastric, and prostate cancer, as well as osteosarcoma, among others, and high expression predicts poor prognosis and poor survival for such patients. Moreover, this molecule can promote proliferation and metastasis, while inhibiting apoptosis in cancer cells. The present review highlights the latest insights into the expression, functional roles, and molecular mechanisms of SNHG7 in different human malignancies.

Long noncoding RNA lnc-ABCA12-3 promotes cell migration, invasion, and proliferation by regulating fibronectin 1 in esophageal squamous cell carcinoma.

Long noncoding RNAs (lncRNAs) have been shown to play important roles in human cancers, including esophageal squamous cell carcinoma (ESCC). We previously demonstrated that a novel lncRNA, lnc-ABCA12-3, was overexpressed in ESCC tissues. However, the exact function of lnc-ABCA12-3 is unknown. In the current study, we aimed to evaluate the expression of lnc-ABCA12-3 in ESCC and to explore the potential mechanism of lnc-ABCA12-3 in cell migration, invasion, and proliferation. We showed that lnc-ABCA12-3 was upregulated in ESCC tumor tissues and cell lines. The increased expression of lnc-ABCA12-3 was positively associated with advanced tumor-node-metastasis stages and poor prognosis. The knockdown of lnc-ABCA12-3 inhibited the cell migration, invasion, and proliferation abilities of KYSE-510 and Eca-109 cells. We also found that fibronectin 1 (FN1) was upregulated in ESCC tumor tissues. The expression of FN1 messenger RNA was positively correlated with the expression of lnc-ABCA12-3 in ESCC tumor tissues. After lnc-ABCA12-3 knockdown, the expression of FN1 was downregulated. In addition, the overexpression of FN1 restored the abilities of cell migration, invasion and proliferation in Eca-109 cells. Further studies indicated that lnc-ABCA12-3 acted as a competing endogenous RNA for miR-200b-3p to regulate FN1 expression. In conclusion, these results suggest that lnc-ABCA12-3 is a novel oncogene in tumorigenesis and that its high expression is related to a poor prognosis for patients with ESCC. lnc-ABCA12-3 promotes cell migration, invasion, and proliferation via the regulation of FN1 in ESCC. Our data suggest that lnc-ABCA12-3 might serve as a potential prognostic biomarker and therapeutic target for ESCC.