N6-methyladenosine-mediated feedback regulation of abscisic acid perception via phase-separated ECT8 condensates in Arabidopsis.

N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic mRNAs, yet how plants recognize this chemical modification to swiftly adjust developmental plasticity under environmental stresses remains unclear. Here we show that m6A mRNA modification and its reader protein EVOLUTIONARILY CONSERVED C-TERMINAL REGION 8 (ECT8) act together as a key checkpoint for negative feedback regulation of abscisic acid (ABA) signalling by sequestering the m6A-modified ABA receptor gene PYRABACTIN RESISTANCE 1-LIKE 7 (PYL7) via phase-separated ECT8 condensates in stress granules in response to ABA. This partially depletes PYL7 mRNA from its translation in the cytoplasm, thus reducing PYL7 protein levels and compromising ABA perception. The loss of ECT8 results in defective sequestration of m6A-modified PYL7 in stress granules and permits more PYL7 transcripts for translation. This causes overactivation of ABA-responsive genes and the consequent ABA-hypersensitive phenotypes, including drought tolerance. Overall, our findings reveal that m6A-mediated sequestration of PYL7 by ECT8 in stress granules negatively regulates ABA perception, thereby enabling prompt feedback regulation of ABA signalling to prevent plant cell overreaction to environmental stresses.

Structural optimization of siRNA conjugates for albumin binding achieves effective MCL1-directed cancer therapy.

The high potential of siRNAs to silence oncogenic drivers remains largely untapped due to the challenges of tumor cell delivery. Here, divalent lipid-conjugated siRNAs are optimized for in situ binding to albumin to improve pharmacokinetics and tumor delivery. Systematic variation of the siRNA conjugate structure reveals that the location of the linker branching site dictates tendency toward albumin association versus self-assembly, while the lipid hydrophobicity and reversibility of albumin binding also contribute to siRNA intracellular delivery. The lead structure increases tumor siRNA accumulation 12-fold in orthotopic triple negative breast cancer (TNBC) tumors over the parent siRNA. This structure achieves approximately 80% silencing of the anti-apoptotic oncogene MCL1 and yields better survival outcomes in three TNBC models than an MCL-1 small molecule inhibitor. These studies provide new structure-function insights on siRNA-lipid conjugate structures that are intravenously injected, associate in situ with serum albumin, and improve pharmacokinetics and tumor treatment efficacy.

Polypeptide N-Acetylgalactosaminyltransferase 14 (GALNT14) as a Chemosensitivity-Related Biomarker for Osteosarcoma.

Purpose: Osteosarcoma is the most common primary bone tumor. Polypeptide N-acetylgalactosaminyltransferase 14 (GALNT14), a member of the N-acetylgalactosaminyltransferase family, has been considered to be associated with various cancers. However, its role in osteosarcoma remains unknown. Here, we aimed to explore the expression and potential mechanism of GALNT14 in osteosarcoma through bioinformatics analysis and in vitro experiments. Methods: We investigated GALNT14 expression in osteosarcoma using GEO, the TIMER database, and clinical samples. Protein-protein interaction (PPI) network analysis on GALNT14 was performed by STRING. TARGET was used to identify differentially expressed genes (DEGs) between high and low GALNT14 expression. The correlation between GALNT14 and cuproptosis-related genes in osteosarcoma was analyzed by R language. The prognostic significance of GALNT14 was examined by Kaplan-Meier survival analysis. Additionally, we inhibited GALNT14 function in an osteosarcoma cell line by transfecting siRNA and subsequently explored the effect on drug sensitivity by CCK-8, clonogenic assay, and flow cytometry. Results: GALNT14 was significantly elevated in osteosarcoma tissue, osteosarcoma cell lines, and metastatic osteosarcoma. PPI analysis revealed that GALNT14 was associated with MUC7, MUC13, MUC5AC, C1GALT1, MUC15, MUC16, MUC1, MUC4, MUC21, and MUC17. In the high GALNT14 expression group, we discovered 81 upregulated DEGs and 73 downregulated DEGs. Functional enrichment analysis of DEGs showed significant enrichment in the Wnt, TGF-ß, Hippo, PI3K signaling pathways and cell adhesion molecules. Expression of cuproptosis-related genes was closely related in osteosarcoma, and GALNT14 expression was significantly positively correlated with FDX1, a key regulator of cuproptosis. Kaplan-Meier survival showed that GALNT14 was linked to poor overall survival and disease-free survival in osteosarcoma. In vitro experiments suggested that GALNT14 was associated with chemotherapy resistance in osteosarcoma. Conclusion: We identified a GALNT family gene, GALNT14, that was highly expressed in osteosarcoma. This gene was closely associated with metastasis, progression, cuproptosis-related genes, and chemosensitivity of osteosarcoma, and showed correlation with poor overall survival and disease-free survival in osteosarcoma.

Structural Optimization of siRNA Conjugates for Albumin Binding Achieves Effective MCL1-Targeted Cancer Therapy.

The high potential for therapeutic application of siRNAs to silence traditionally undruggable oncogenic drivers remains largely untapped due to the challenges of tumor cell delivery. Here, siRNAs were optimized for in situ binding to albumin through C18 lipid modifications to improve pharmacokinetics and tumor delivery. Systematic variation of siRNA conjugates revealed a lead structure with divalent C18 lipids each linked through three repeats of hexaethylene glycol connected by phosphorothioate bonds. Importantly, we discovered that locating the branch site of the divalent lipid structure proximally (adjacent to the RNA) rather than at a more distal site (after the linker segment) promotes association with albumin, while minimizing self-assembly and lipoprotein association. Comparison to higher albumin affinity (diacid) lipid variants and siRNA directly conjugated to albumin underscored the importance of conjugate hydrophobicity and reversibility of albumin binding for siRNA delivery and bioactivity in tumors. The lead conjugate increased tumor siRNA accumulation 12-fold in orthotopic mouse models of triple negative breast cancer over the parent siRNA. When applied for silencing of the anti-apoptotic oncogene MCL-1, this structure achieved approximately 80% MCL1 silencing in orthotopic breast tumors. Furthermore, application of the lead conjugate structure to target MCL1 yielded better survival outcomes in three independent, orthotopic, triple negative breast cancer models than an MCL1 small molecule inhibitor. These studies provide new structure-function insights on optimally leveraging siRNA-lipid conjugate structures that associate in situ with plasma albumin for molecular-targeted cancer therapy.

Five critically ill pregnant women/parturients treated with extracorporeal membrane oxygenation.

BACKGROUND: Maternal mortality has always been a major medical concern. Recently, the successful application of extracorporeal membrane oxygenation (ECMO) technology in the rescue of near-death patients has been reported. CASE PRESENTATION: This study retrospectively analyzed 5 cases of critically ill pregnant women/parturients treated with ECMO for respiratory and circulatory failure in the Wuxi People's Hospital from 2018 to 2020. The mean age of the 5 cases was 30.2 years. Among them, Cases 1 and 5 were treated with Venoarterial (VA) ECMO. Case 1 was diagnosed with congenital heart disease, atrial septal defect, and severe pulmonary hypertension. VA ECMO was applied before cesarean section and was successfully removed after double lung transplantation, but the patient died 10 months after delivery from lung infection. While Case 5 was diagnosed with systemic lupus erythematosus, lupus nephritis, thrombotic vascular disease, HELLP syndrome, and cerebral hemorrhage. VA ECMO was applied 39 days after cesarean section, and the patient died 40 days after delivery due to multiple organ failure. Cases 3 and 4 were treated with Venovenous (VV) ECMO. Case 3 was diagnosed with refractory postpartum hemorrhage, and Case 4 was diagnosed with postpartum hypoglycemic coma, aspiration pneumonia, and shock. They were treated with VV ECMO after delivery, and all survived after successful evacuation. Another Case (Case 2) was diagnosed with postpartum pelvic infection, sepsis and septic shock, and was treated with VA ECMO at 15 days after delivery. The patient changed to VV ECMO at 30 days after delivery due to significant improvement in heart function and poor lung function, but eventually died of multiple organ failure. For the 5 cases, the mean duration of ECMO was 8.7 days, the mean duration of intensive care was 22.0 days, and the mean length of hospital stay was 57.6 days. As a result, 3 patients gradually returned to normal with significant improvement in ventilation and oxygenation after ECMO treatment. CONCLUSIONS: ECMO technology can be used to treat some of the critical obstetric patients with respiratory and circulatory failure that is ineffective to conventional treatment, but it has no therapeutic effect on the primary disease.

Study of tRNA-Derived Fragment tRF-20-S998LO9D in Pan-Cancer.

Objective: The purpose is to study the effect of tRNA-derived fragments (tRFs) on pan-cancer through bioinformatics. Methods: The expression information of tRF-20-S998LO9D, a type of tRF-5, was retrieved through MINTbase in pan-cancer and verified by qPCR. We preliminarily explored the effect of tRF-20-S998LO9D on cell proliferation in breast cancer and lung cancer cell lines. Then an online KM-plotter provided by OncotRF was used to discover the prognostic significance. GO/KEGG analyses were executed to predict the potential mechanism of tRF-20-S998LO9D in cancer. Results: We found that tRF-20-S998LO9D was highly expressed in a variety of cancers like breast invasive carcinoma, head and neck squamous cell carcinoma, kidney renal clear cell carcinoma, lung squamous cell carcinoma, pheochromocytoma and paraganglioma, and uterine corpus endometrial carcinoma. Inhibition of tRF-20-S998LO9D led to reduced cell proliferation in breast cancer (MCF-7) and lung squamous cell carcinoma (SK-MES-1) cells. Elevated tRF-20-S998LO9D indicated poor prognosis in a variety of cancers. tRF-20-S998LO9D might be involved in multiple cancer-related pathways. Conclusion: We concluded that tRF-20-S998LO9D was upregulated and negatively correlated with prognosis of a variety of cancers. It may be a potential cancer-promoting marker in pan-cancer.

BRD7 Stabilizes P53 via Dephosphorylation of MDM2 to Inhibit Tumor Growth in Breast Cancer Harboring Wild-type P53.

Bromodomain-containing protein 7 (BRD7) was found to be down-expressed in nasopharyngeal carcinoma as well as breast cancer and to function as a potential tumor suppressor. BRD7 interacts with p53 and is required for p53-dependent oncogene-induced senescence. However, the mechanism how BRD7 functions as tumor suppressor roles in breast cancer remains unclear. MTT, colony formation assay, cell cycle, cell apoptosis, and tumorigenicity assays were performed to evaluate the biological functions of BRD7 in breast cancer cells in vitro and in vivo. Real-time PCR, western blot, luciferase reporter gene assays, and co-immunoprecipitation were used to examine the gene expression, transcription activation and protein-protein interaction. We reported that BRD7 effectively suppressed cell proliferation and tumor growth in vitro and in vivo. In addition, BRD7 increased p53 protein stability through ubiquitin-dependent proteasome pathway and regulated the expression of p53 downstream target genes by activating its transcriptional activity in breast cancers harboring wild-type p53. Mechanistically, BRD7 decreased phosphorylation and activation of MDM2 via inactivating its upstream kinase AKT depending on the bromodomain of BRD7, therefore BRD7 significantly reduced the amounts of phosphorylated MDM2 binding with p53 eventually decreasing ubiquitination level of p53. Furthermore, silencing the expression of p53 at least partly reversed the inhibition effect of BRD7 on cell proliferation and tumor growth in vitro and in vivo. Our studies identify that BRD7 stabilizes p53 by inhibiting the phosphorylation of MDM2 via AKT pathway dependent on its bromodomain to function as a tumor suppressor in breast cancer harboring wild-type p53.

A novel epigenetic regulation of circFoxp1 on Foxp1 in colon cancer cells.

Foxp1 is a tumor suppressor in colon cancer. However, circFoxp1 derived from Foxp1 is an oncogene. In this study, we aim to investigate the role of circFoxp1 in colon cancer and the regulatory mechanism between circFoxp1 and Foxp1. 78 human colon tumor tissues and the matched paracancerous tissues were collected. Quantitative polymerase chain reaction, immunohistochemistry, quantitative methylation-specific PCR, chromatin immunoprecipitation assay, CCK-8 assay, and Tumor xenograft in nude mice were performed. The expression of circFoxp1 was increased and Foxp1 was reduced in colon cancer tissues, which were associated with a poor overall survival rate of the patients with colon cancer. CircFoxp1 recruited DNMT1 to the promoter of Foxp1, leading to promotor hypermethylation, thereby inhibiting Foxp1 transcription. Interfering circFoxp1 by siRNA in SW620 cells significantly inhibited cell viability, while knockdown Foxp1 expression partially restored SW620 cell viability. In addition, knockdown of circFoxp1 significantly sensitized colon cancer cells to Capecitabine in vitro and vivo through regulating Foxp1. We discovered a novel epigenetic pathway that circFoxp1 regulated Foxp1 in colon cancer cells. CircFoxp1 may regulate DNA methylation and demethylation to coordinate colon cancer cell proliferation and participate in chemotherapy drug responses. Therefore, circFoxp1 may be a potential therapeutic target for colon cancer.

Diagnostic value of exosomal circMYC in radioresistant nasopharyngeal carcinoma.

BACKGROUND: The relationship between circulating exosomal circular RNA (circRNA) and prognosis of patients with nasopharyngeal carcinoma (NPC) remain unknown. This study focused on the expression of exosomal circMYC and its relationship with the recurrence and prognosis of patients with NPC. METHODS: The circulating exosomes were obtained from 210 patients with NPC. Quantitative polymerase chain reaction, 5-ethynyl-2'-deoxyuridine (EdU) staining, colony formation, and bioinformatic analysis were performed. RESULTS: Circulating exosomal circMYC was significantly increased in patients with NPC and was associated with tumor size, lymph node metastasis, TNM stage, survival rate, and disease recurrence. Gain-functional and loss-functional experiments revealed that overexpression of circMYC promoted cell proliferation and reduce radiosensitivity, while knockdown of circMYC inhibited cell proliferation and enhanced radiotherapy. CONCLUSION: circMYC is an oncogene in NPC cells and can enhance the radiotherapy resistance of NPC cells. Circulating exosomal circMYC can be used as a potential therapeutic target for NPC.

Genome-Wide Identification and Expression Profiling of Monosaccharide Transporter Genes Associated with High Harvest Index Values in Rapeseed (Brassica napus L.).

Sugars are important throughout a plant's lifecycle. Monosaccharide transporters (MST) are essential sugar transporters that have been identified in many plants, but little is known about the evolution or functions of MST genes in rapeseed (Brassica napus). In this study, we identified 175 MST genes in B. napus, 87 in Brassica oleracea, and 83 in Brassica rapa. These genes were separated into the sugar transport protein (STP), polyol transporter (PLT), vacuolar glucose transporter (VGT), tonoplast monosaccharide transporter (TMT), inositol transporter (INT), plastidic glucose transporter (pGlcT), and ERD6-like subfamilies, respectively. Phylogenetic and syntenic analysis indicated that gene redundancy and gene elimination have commonly occurred in Brassica species during polyploidization. Changes in exon-intron structures during evolution likely resulted in the differences in coding regions, expression patterns, and functions seen among BnMST genes. In total, 31 differentially expressed genes (DEGs) were identified through RNA-seq among materials with high and low harvest index (HI) values, which were divided into two categories based on the qRT-PCR results, expressed more highly in source or sink organs. We finally identified four genes, including BnSTP5, BnSTP13, BnPLT5, and BnERD6-like14, which might be involved in monosaccharide uptake or unloading and further affect the HI of rapeseed. These findings provide fundamental information about MST genes in Brassica and reveal the importance of BnMST genes to high HI in B. napus.

Six-mRNA risk score system and nomogram constructed for patients with ovarian cancer.

Platinum is a commonly used drug for the treatment of ovarian cancer (OC). The aim of the current study was to design and construct a risk score system for predicting the prognosis of patients with OC receiving platinum chemotherapy. The mRNA sequencing data and copy number variation (CNV) information (training set) of patients with OC were downloaded from The Cancer Genome Atlas database. A validation set, GSE63885, was obtained from Gene Expression Omnibus database. The differentially expressed genes (DEGs) and CNV genes (DECNs) between platinum-resistant and platinum-sensitive groups were identified using the limma package. The intersection between DEGs and DECNs were selected. Cox regression analysis was used to identify the genes and clinical factors associated with prognosis. Risk score system assessment and nomogram analysis were performed using the survival and rms packages in R. Gene Set Enrichment Analysis was used to identify the enriched pathways in high and low risk score groups. From 1,144 DEGs and 1,864 DECNs, 48 genes that occurred in the two datasets were selected. A total of six independent prognostic genes (T-box transcription factor T, synemin, tektin 5, growth differentiation factor 3, solute carrier family 22 member 3 and calcium voltage-gated channel subunit α1 C) and platinum response status were revealed to be associated with prognosis. Based on the six independent prognostic genes, a risk score system was constructed and assessed. Nomogram analysis revealed that the patients with the sensitive status and low risk scores had an improved prognosis. Furthermore, the current study revealed that the 574 DEGs identified were involved in eight pathways, including chemokine signaling pathway, toll-like receptor signaling pathway, cytokine-cytokine receptor interaction, RIG I like receptor signaling pathway, natural killer cell mediated cytotoxicity, apoptosis, T cell receptor signaling pathway and Fc ε receptor 1 signaling pathway. The six-mRNA risk score system designed in the present study may be used as prognosis predictor in patients with OC, whereas the nomogram may be valuable for identifying patients with OC who may benefit from platinum chemotherapy.

Removal of residual functionalized ionic liquids from water by ultrasound-assisted zero-valent iron/activated carbon.

Numerous applications of ionic liquids (ILs) are often accompanied by the generation of aqueous wastes. Due to the high toxicity and poor biodegradability of ILs, effective chemical treatment is of great importance for their removal from aqueous solution. In this work, an ultrasound-assisted zero-valent iron/activated carbon (US-ZVI/AC) micro-electrolysis technique was used to degrade residual functionalized ILs, 1-butyl-3-methyl benzimidazolium bromide ([BMBIM]Br) and 1-allyl-3-methylimidazolium chloride ([AMIM]Cl) in aqueous solution, and the degradation degree, degradation kinetics and possible degradation pathways were investigated. It was shown that the degradation of these functionalized ILs was highly efficient in the US-ZVI/AC system, and the degradation degree was as high as 96.1% and 92.9% in 110 min for [BMBIM]Br and [AMIM]Cl, respectively. The degradation of [BMBIM]Br could be described by the second-order kinetics model, and [BMBIM]+ was decomposed in two ways: (i) sequential cleavage of N-alkyl side chain of the cation produced three intermediates; (ii) the 2-positioned H atoms of the benzimidazolium ring were first oxidized, and then the imidazolium ring was opened. The degradation of [AMIM]Cl followed the first-order kinetics rule, and the 2,4,5-positioned H atoms of the imidazolium ring were oxidized to induce ring opening. In addition, the removal of total organic carbon was found to be >87%, which indicates that most of the ILs was mineralized in the degradation process. These results suggest that ultrasound-assisted ZVI/AC micro-electrolysis is highly effective for the removal of residual functionalized ILs from aqueous environment.

Bromodomain­containing protein 7 sensitizes breast cancer cells to paclitaxel by activating Bcl2­antagonist/killer protein.

Our previous study demonstrated that bromodomain­containing protein 7 (BRD7) inhibits cell proliferation and tumor growth, restoring the expression of B­cell lymphoma 2 antagonist/killer (Bak) sensitized breast cancer cells to paclitaxel. However, the association between BRD7 and paclitaxel sensitization, as well as BRD7 and Bak in breast cancer remains unknown. In the present study, immunochemical staining was performed to measure the expression of BRD7 and Bak in breast cancer tissues. Cell Counting Kit­8 assay, flow cytometry and tumor xenograft procedures were performed to evaluate the biological role of BRD7 and Bak in breast cancer cells. Western blotting, reverse transcription­quantitative polymerase chain reaction, chromatin immunoprecipitation and luciferase reporter assays were also performed. BRD7 was positively correlated with Bak levels in breast cancer tissues, and the survival rate of patients with low Bak and BRD7 expression was significantly lower than that of patients with high Bak and BRD7 expression. In addition, BRD7 activated Bak promoter activity and induced Bak expression in an indirect manner. Furthermore, ectopic expression of BRD7 inhibited cell proliferation, tumor growth and sensitized cancer cells to paclitaxel, while knockdown of Bak abolished BRD7­mediated inhibitory effects on cell proliferation and paclitaxel sensitization in breast cancer cells whether in vitro and in vivo. The results demonstrated that BRD7 inhibits cell proliferation and sensitizes breast cancer cells to paclitaxel by activating Bak; they also provide promising targets for the diagnosis and treatment of breast cancer.

Dendrimer-paclitaxel complexes for efficient treatment in ovarian cancer: study on OVCAR-3 and HEK293T cells.

The present paper investigates the enhancement of the therapeutic effect of Paclitaxel (a potent anticancer drug) by increasing its cellular uptake in the cancerous cells with subsequent reduction in its cytotoxic effects. To fulfill these goals the Paclitaxel (PTX)-Biotinylated PAMAM dendrimer complexes were prepared using biotinylation method. The primary parameter of Biotinylated PAMAM with a terminal HN2 group - the degree of biotinylation - was evaluated using HABA assay. The basic integrity of the complex was studied using DSC. The Drug Loading (DL) and Drug Release (DR) parameters of Biotinylated PAMAM dendrimer-PTX complexes were also examined. Cellular uptake study was performed in OVCAR-3 and HEK293T cells using fluorescence technique. The statistical analysis was also performed to support the experimental data. The results obtained from HABA assay showed the complete biotinylation of PAMAM dendrimer. DSC study confirmed the integrity of the complex as compared with pure drug, biotinylated complex and their physical mixture. Batch 9 showed the highest DL (12.09%) and DR (70%) for 72 h as compared to different concentrations of drug and biotinylated complex. The OVCAR-3 (cancerous) cells were characterized by more intensive cellular uptake of the complexes than HEK293T (normal) cells. The obtained experimental results were supported by the statistical data. The results obtained from both experimental and statistical evaluation confirmed that the biotinylated PAMAM NH2 dendrimer-PTX complex not only displays increased cellular uptake but has also enhanced release up to 72 h with the reduction in cytotoxicity.

Genome-Wide Identification of MicroRNAs in Response to Cadmium Stress in Oilseed Rape (Brassica napus L.) Using High-Throughput Sequencing.

MicroRNAs (miRNAs) have important roles in regulating stress-response genes in plants. However, identification of miRNAs and the corresponding target genes that are induced in response to cadmium (Cd) stress in Brassica napus remains limited. In the current study, we sequenced three small-RNA libraries from B. napus after 0 days, 1 days, and 3 days of Cd treatment. In total, 44 known miRNAs (belonging to 27 families) and 103 novel miRNAs were identified. A comprehensive analysis of miRNA expression profiles found 39 differentially expressed miRNAs between control and Cd-treated plants; 13 differentially expressed miRNAs were confirmed by qRT-PCR. Characterization of the corresponding target genes indicated functions in processes including transcription factor regulation, biotic stress response, ion homeostasis, and secondary metabolism. Furthermore, we propose a hypothetical model of the Cd-response mechanism in B. napus. Combined with qRT-PCR confirmation, our data suggested that miRNAs were involved in the regulations of TFs, biotic stress defense, ion homeostasis and secondary metabolism synthesis to respond Cd stress in B. napus.

Genome-Wide Identification, Evolutionary and Expression Analyses of the GALACTINOL SYNTHASE Gene Family in Rapeseed and Tobacco.

Galactinol synthase (GolS) is a key enzyme in raffinose family oligosaccharide (RFO) biosynthesis. The finding that GolS accumulates in plants exposed to abiotic stresses indicates RFOs function in environmental adaptation. However, the evolutionary relationships and biological functions of GolS family in rapeseed (Brassica napus) and tobacco (Nicotiana tabacum) remain unclear. In this study, we identified 20 BnGolS and 9 NtGolS genes. Subcellular localization predictions showed that most of the proteins are localized to the cytoplasm. Phylogenetic analysis identified a lost event of an ancient GolS copy in the Solanaceae and an ancient duplication event leading to evolution of GolS4/7 in the Brassicaceae. The three-dimensional structures of two GolS proteins were conserved, with an important DxD motif for binding to UDP-galactose (uridine diphosphate-galactose) and inositol. Expression profile analysis indicated that BnGolS and NtGolS genes were expressed in most tissues and highly expressed in one or two specific tissues. Hormone treatments strongly induced the expression of most BnGolS genes and homologous genes in the same subfamilies exhibited divergent-induced expression. Our study provides a comprehensive evolutionary analysis of GolS genes among the Brassicaceae and Solanaceae as well as an insight into the biological function of GolS genes in hormone response in plants.

Impact of perioperative blood transfusion on survival of patients undergoing laparoscopic gastrectomy for gastric cancer.

PURPOSE: Previous studies have suggested that perioperative blood transfusion is associated with poor prognosis in patients undergoing radical gastrectomy for gastric cancer. The purpose of this study was to evaluate the impact of blood transfusion on the long-term survival of such patients. METHODS: Short- and long-term outcomes were retrieved from a prospectively collected database of patients who underwent laparoscopic gastrectomy with radical intent for gastric cancer. RESULTS: A total of 309 patients who underwent laparoscopic radical gastrectomy were evaluated. Sixty-one (19.7%) received blood transfusions during or within 30 days after gastrectomy. These patients were typically older, had lower preoperative hemoglobin levels, had a more advanced cancer stage, had more than two comorbidities, had a higher rate of postoperative 30-day complications, and had a higher conversion rate. The overall survival (OS) (p=0.040) and disease-free survival (DFS) (p=0.004) were significantly decreased in patients who received blood transfusions. Multivariate analysis revealed that perioperative blood transfusion was not independently associated with decreased OS and DFS but that cancer stage and having more than two comorbidities were independent risk factors. CONCLUSION: Perioperative blood transfusion was associated with decreased OS and DFS in this patient series, but this apparently reflected the relatively poor medical condition of these patients requiring gastrectomy and was not a causative relationship.

Long Noncoding RNA LINC0086 Functions as a Tumor Suppressor in Nasopharyngeal Carcinoma by Targeting miR-214.

Nasopharyngeal carcinoma (NPC) is a distinct head and neck cancer, which is occurring at a high frequency in Southern China. Emerging studies have shown that long noncoding RNAs (lncRNAs) play a critical role in carcinogenesis and progression. In this study, we established a comprehensive lncRNA profile in NPC and found that 35 lncRNAs were differentially expressed in NPC. We found that LINC0086 was decreased in NPC patient serum samples and tissues. The Kaplan-Meier survival curve showed that patients with high LINC0086 expression had a higher survival rate than those with low LINC0086 expression. LINC0086 expression was associated with NPC histological grade, lymph node metastasis, and clinical stage. Upregulation of LINC0086 inhibited cancer cell proliferation and promoted apoptosis. In addition, upregulation of LINC0086 dramatically decreased the expression of miR-214, an oncogene in several cancers, in C666-1 and HK-1 cells. An miR-214 binding site was found in the 3'-UTR of LINC0086. We also validated that both miR-214 and LINC0086 presented in the RISC complex, demonstrating that LINC0086 could decrease miR-214 expression by directly interacting with miR-214. Furthermore, the suppressive effects of LINC0086 on NPC cell growth were reversed by overexpression of miR-214 in vitro and in vivo. Thus, our study reports a novel mechanism underlying NPC carcinogenesis and provides a potential novel diagnosis and treatment biomarker for NPC.