Role of sphingosine-1-phosphate receptors in the tumor microenvironment: prospects for cancer immunotherapy.

OBJECTIVE: Sphingosine-1-phosphate (S1P) is a sphingolipid protein with anti-apoptotic and pro-survival effects on cancer cells via S1P receptors (S1PRs); however, the role of S1PRs in the tumor microenvironment and immune invasion is still unclear. This study investigated the relationship between S1PR expressions and patient survival and clinical manifestations with respect to the tumor microenvironment and immune infiltration. MATERIALS AND METHODS: The expression levels of five S1PRs were obtained from The Cancer Genome Atlas pan-cancer database and the Kaplan-Meier survival analysis was performed. We predicted the relationship between S1PRs expression levels and patient survival using the univariate Cox proportional hazard regression model. Subsequently, we analyzed correlations between S1PRs expression and infiltrating immune cell subtypes using the Kolmogorov-Smirnov test and the infiltration levels of immune and stromal cells in each tumor using the ESTIMATE algorithm and Spearman's test. RESULTS: The five S1PRs exhibited significant heterogeneity in their expression levels. The expression levels correlated with overall patient survival; however, anti-apoptotic or pro-apoptotic features varied depending on the cancer type. The variable effects of S1PRs on tumors may be related to TGF-ß levels. Our results suggest that S1PRs exert distinct influences on the tumor stem cell index and chemotherapeutic drug sensitivity. CONCLUSIONS: This research provides comprehensive information on the importance of S1PRs in the immune microenvironment, stemness score, sensitivity of human cancer drugs, and cancer prognosis. Interestingly, our findings indicate variations in the expression levels and functions of different S1PR family members. This study highlights S1PRs as potential new targets for antitumor (adjuvant) therapy.

Integrative analyses of radiation-related genes and biomarkers associated with breast cancer.

OBJECTIVE: In addition to significantly reducing breast cancer recurrence risk, radiotherapy also prolongs patients' lives. However, radiotherapy-related genes and biomarkers still remain poorly understood. The present study aimed to identify radiation-associated genes in breast cancer. MATERIALS AND METHODS: Breast cancer data were downloaded from Gene Expression Omnibus (GEO) and UCSC Xena database. The gene ontology (GO) enrichment and gene set enrichment analysis (GSEA) were performed for annotation and integrated discovery. Protein-protein interaction (PPI) network was constructed by STRING database and hub genes were identified. Then, immunohistochemistry and tissue expression of key genes was analyzed by using the Human Protein Atlas (HPA) and GEPIA database. Genes associated with prognosis were identified by performing univariate cox analysis. RESULTS: We identified 341 differentially expressed genes related to radiotherapy in breast cancer patients. PPI analysis revealed a total of 129 nodes and 516 interactions and identified five hub genes (EGFR, FOS, ESR1, JUN, and IL6). In addition, 11 SDEGs THBS1, SERPINA11, NFIL3, METTL7A, KCTD12, HSPA6, EGR1, DDIT4, CCDC3, C11orf96, and BCL2A1 candidate genes can be used as potential diagnostic markers. The calibration curve and ROC indicate good probability consistencies of 3-years and 5-year survival rates of patients between estimation and observation. CONCLUSIONS: Our findings provide novel insight into the functional characteristics of breast cancer through integrative analysis of GEO data and suggest potential biomarkers and therapeutic targets for breast cancer.

VASPIN reduces inflammation and endoplasmic reticulum stress of renal tubular epithelial cells by inhibiting HMGB1 and relieves renal ischemia-reperfusion injury.

OBJECTIVE: Renal ischemia-reperfusion injury (IRI) is a clinically common issue and the resulting acute kidney injury (AKI) seriously threatens the patient's life. Therefore, prevention and treatment of renal IRI are the key to alleviating AKI in such patients. The purpose of this study was to explore the effects of VASPIN on mouse renal IRI and human renal proximal tubular epithelial cells (HK-2 cells) to provide a new direction for the treatment of clinical renal IRI. MATERIALS AND METHODS: C57/BL6 mice were used to construct a renal IRI model and recombinant mouse VASPIN was subcutaneously injected to determine whether VASPIN can alleviate renal IRI in mice by histological examination and detection of mouse urine and serum related indicators. In addition, HK-2 cells were cultured and an IRI model was constructed at the cellular level by hypoxia reoxygenation to examine the effect and mechanism of VASPIN on endoplasmic reticulum stress (ERS) in HK-2 cells. RESULTS: Results revealed that in VASPIN-treated mice, edema of renal tubular epithelial cells was significantly improved and renal injury markers netrin-1 and L-FAPB were decreased in urine. In addition, VASPIN also reduced the expression of inflammatory factors in mouse serum and the level of oxidative stress in kidney tissue. The expression of ERS-related molecules (GRP78, ATF6, caspase12, and CHOP) in HK-2 cells treated with VASPIN was significantly reduced and VASPIN decreased the expression of the pro-inflammatory factor HMGB1. Moreover, VASPIN promoted the activity of the Nrf2/ARE/HO-1 signaling pathway and inhibited the NF-кB signaling pathway by inhibiting HMGB1. CONCLUSIONS: VASPIN reduces inflammation and ERS levels in kidney tissue and attenuates renal IRI by activating the Nrf2/ARE/HO-1 signaling pathway and inhibiting the NF-кB signaling pathway via inhibition of HMGB1.

LINC00707 promotes cell proliferation and invasion of colorectal cancer via miR-206/FMNL2 axis.

OBJECTIVE: Long non-coding RNAs (lncRNAs) have been verified to participate in the regulation of colorectal cancer (CRC). However, the role of LINC00707 in CRC still remains unknown. Here, we aim to study the role of LINC00707 in CRC. PATIENTS AND METHODS: LINC00707 expression in 97 pairs of CRC tissues and adjacent normal tissues was determined by the quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). LINC00707 overexpression or knockdown in SW620 or HCT116 cells was achieved by lentivirus transfection. The proliferation and cell circle progression of established cells were detected by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. Cell invasion and migration abilities were studied by transwell assay. Dual-luciferase assay and Western blot was used to verify the underlying mechanism of LINC00707 in CRC. Nude mice were obtained to identify the in vivo function of LINC00707 in CRC. RESULTS: LINC00707 was significantly over-expressed in CRC tissues and cell lines. Up-regulation of LINC00707 promoted cell proliferation, cell cycle progression, invasion, and migration of SW620 cells. Conversely, down-regulation of LINC00707 reduced cell growth and metastasis of HCT116 cells. MiR-206 was verified as a direct target of LINC00707, and its function was inhibited by LINC00707. FMNL2 was a target for miR-206 in CRC cells. Meanwhile, LINC00707 promoted tumor growth of CRC in vivo. CONCLUSIONS: LINC00707 was up-regulated in CRC tissues and cells, which promoted cell proliferation and metastasis via sponging miR-206 to increase FMNL2 expression. This might provide a novel target for the biological treatment of CRC.

Primary abdominopelvic desmoplastic small round cell tumor: CT and correlated clinicopathologic features.

OBJECTIVE: To evaluate the CT characteristics of primary abdominopelvic desmoplastic small round cell tumor (DSCRT) and investigate the relation between radiologic features and corresponding clinicopathologic features. PATIENTS AND METHODS: A cohort study was performed on 12 abdominopelvic DSCRT patients, the preoperative computed tomography (CT) and contrast enhancement CT scan were performed in all cases. Tumor dimension, location, calcification, organs involvement, metastasis and enhancement characteristics were retrospectively evaluated and catalogued. Histopathology and serial immunological histological chemistry (IHC) studies were as diagnostic reference standard, all clinicopathological and radiological data were analyzed with emphasis on the corresponding imaging findings. RESULTS: Abdominopelvic DSRCT mainly affects young males (male to female was 2:1), Predominantly, two individualized CT subtype patterns were noted according to its characteristic features and the most common imaging findings are extensively disseminated masses in the peritoneal cavity and/or mesentery with slight enhancement after administration of contrast (subtype 1, 9/12; 75%), the type was in correlated with the histopathologic findings of a large stromal component and scare of vessels or tumor cells. In subtype 2 (3/12; 25%), the tumor was solitary and bulky soft-tissue mass localized in retroperitoneum or retrovesical space, it manifested as heterogeneous enhancement which correlated well with the presence of abundance of microvessels and tumor cells. CONCLUSIONS: Radiologically, abdomino-pelvic DSRCT is lack of pathognomonic CT character, the most common CT finding is multiple soft tissue masses or solitary bulky lesion inclined to extensively peritoneal and mesenteric spread with heterogeneous enhancement. These radiological findings are related to different histological compositions, awareness of these radiological features may facilitate the CT diagnosis.

Evaluation of cellulolytic activity in insect digestive fluids.

Efficient and low-cost cellulolytic enzymes are urgently needed to degrade recalcitrant plant biomass during the industrial production of lignocellulosic biofuels. Here, the cellulolytic activities in the gut fluids of 54 insect species that belong to 7 different taxonomic orders were determined using 2 different substrates, carboxymethyl cellulose (CMC) (approximating endo-ß-1,4-glucanase) and filter paper (FP) (total cellulolytic activities). The use of CMC as the substrate in the zymogram analysis resulted in the detection of distinct cellulolytic protein bands. The cellulolytic activities in the digestive system of all the collected samples were detected using cellulolytic activity analysis. The highest CMC gut fluid activities were found in Coleoptera and Orthoptera, while FP analysis indicated that higher gut fluid activities were found in several species of Coleoptera and Lepidoptera. In most cases, gut fluid activities were higher with CMC than with FP substrate, except for individual Lepidoptera species. Our data indicate that the origin of cellulolytic enzymes probably reflects the phylogenetic relationship and feeding strategies of different insects.