ALOX5AP suppresses osteosarcoma progression via Wnt/ß-catenin/EMT pathway and associates with clinical prognosis and immune infiltration.

Osteosarcoma (OS) is one of the most common malignant neoplasms in children and adolescents. Immune infiltration into the microenvironment of the tumor has a positive correlation with overall survival in patients with OS. The purpose of this study was to search for potential diagnostic markers that are involved in immune cell infiltration for OS. Patients with OS who acquired metastases within 5 years (n = 34) were compared to patients who did not develop metastases within 5 years (n = 19). Differentially expressed genes (DEGs) were tested for in both patient groups. To discover possible biomarkers, the LASSO regression model and the SVM-RFE analysis were both carried out. With the assistance of CIBERSORT, the compositional patterns of the 22 different types of immune cell fraction in OS were estimated. In this research, a total of 33 DEGs were obtained: 33 genes were significantly downregulated. Moreover, we identified six critical genes, including ALOX5AP, HLA-DOA, HLA-DMA, HLA-DRB4, HCLS1 and LOC647450. ROC assays confirmed their diagnostic value with AUC > 0.7. In addition, we found that the six critical genes were associated with immune infiltration. Then, we confirmed the expression of ALOX5AP was distinctly decreased in OS specimens and cell lines. High expression of ALOX5AP predicted an advanced clinical stage and overall survival of OS patients. Functionally, we found that overexpression of ALOX5AP distinctly suppressed the proliferation, migration, invasion and EMT via modulating Wnt/ß-catenin signaling. Overall, we found that ALOX5AP overexpression inhibits OS development via regulation of Wnt/ß-catenin signaling pathways, suggesting ALOX5AP as a novel molecular biomarker for enhanced therapy of OS.

MiR-1224 Acts as a Prognostic Biomarker and Inhibits the Progression of Gastric Cancer by Targeting SATB1.

OBJECTIVE: MiR-1224 has been reported to exhibit abnormal expression in several tumors. However, the expressing pattern and roles of miR-1224 in gastric cancer (GC) remain unclear. Our current research aimed to explore the potential involvement of miR-1224 in the GC progression. MATERIALS AND METHODS: The expression of miR-1224 was examined in tissue samples of 128 GC patients and cell lines by RT-PCR. Besides, the associations of miR-1224 expressions with clinicopathologic features and prognosis of GC patients were analyzed. Then, the possible influences of miR-1224 on cell proliferation and cell migration were determined. Afterward, the molecular target of miR-1224 was identified using bioinformatics assays and confirmed experimentally. Finally, RT-PCR and Western blot assays were performed to investigate the effect of the abnormal miR-1224 expression on the EMT and Wnt/ß-catenin pathway. RESULTS: miR-1224 was lowly expressed in the GC specimens and cell lines due to T classification and TNM stage. Survival assays demonstrated that GC patients with low expressions of miR-1224 possessed poor overall survivals. Moreover, in vitro and in vivo assays revealed that the overexpression of miR-1224 inhibited cell proliferation, migration, and invasion in GC cells. SATB homeobox 1 (SATB1) was verified as a direct target of miR-1224 in GC. Furthermore, ß-catenin and c-myc were significantly inhibited in miR-1224-overexpression cells. CONCLUSIONS: Our findings highlight the potential of miR-1224 as a therapeutic target and novel biomarker for GC patients.

ZNF418 overexpression protects against gastric carcinoma and prompts a good prognosis.

BACKGROUND: This study aimed to investigate the prognostic power of zinc-finger protein 418 (ZNF418) in gastric cancer (GC) and its potential role in GC development and progression. PATIENTS AND METHODS: A total of 10 GC patients' individual plasmas were collected and screened for dysregulated mRNA using human microarray. Among these dysregulated mRNAs, ZNF418 was found to be significantly downregulated in IIIA-IV stage GC patients compared to IA-IIA stage GC patients. Subsequently, the ZNF418 levels were detected by quantitative reverse transcription-polymerase chain reaction in both GC plasmas and tissues in a larger sample, and the association between ZNF418 expression level and clinicopathological features as well as overall survival (OS) of GC patients was further analyzed. Finally, a network of ZNF418 interactions with other molecules was predicated in STRING and GEPIA databases. RESULTS: Human mRNA microarray was performed to screen for abnormally expressed mRNAs between five IIIA-IV stage GC patients' plasma and five IA-IIA stage GC patients' plasma. A total of 662 mRNAs were differentially expressed in the IIIA-IV stage GC plasma vs IA-IIA stage GC plasma among all the candidate mRNAs according to the Student's t-test. Results showed that a decrease in the ZNF418 expression level was associated with the presence of GC and also with higher tumor-node-metastasis stage and lower OS rates compared with that in adjacent noncancerous tissues. Cox regression analysis results demonstrated that the OS was independently correlated with ZNF418 expression. Finally, the prediction results showed that a total of eight mRNAs might have an interaction with ZNF418 in both STRING and GEPIA databases. CONCLUSION: ZNF418 was first identified to be significantly downregulated in GC. Our study indicated that ZNF418 might serve as a novel biomarker for GC and was involved in GC development.

[Characteristics of Enteromorpha prolifera Biochars and Their Adsorption Performance and Mechanisms for Cr(â ¥)].

This study aims to understand the recycling process of Enteromorpha prolifera by using the slow pyrolysis technology to prepare biochars under different temperatures and by characterizing the physicochemical properties of biochars. The results showed that a relatively high level pyrolysis of Enteromorpha prolifera could be reached when the temperature was up to 400℃. The yield rate and the ash content of biochars were negatively correlated with the pyrolysis temperature, while the carbon content was positively correlated. The specific surface area of Enteromorpha prolifera biochars was in the range of 44.54-317.82 m2·g-1. The biochar surface was in the shape of a honeycomb and rich in oxygen-containing functional groups, such as hydroxyl (-OH) and carboxyl (-COOH) groups. The adsorption experiments revealed that the adsorption of Cr(Ⅵ) onto Enteromorpha prolifera biochars followed the pseudo-second-order kinetics equation and Langmuir isotherm, indicating that the adsorption process was controlled by the fast reaction process and governed by monomolecular and chemical adsorption. The optimal pH for Cr(Ⅵ) adsorption onto Enteromorpha prolifera biochars was 2 and their adsorption capabilities were in the order of BC400 > BC700 > BC600 > BC500 > BC300 (the adsorption capacity of BC400 was 4.79 mg·g-1). The adsorption mechanism included the electrostatic interactions between biochar and anions (HCrO-4 and Cr2O2-7) and the complexation of oxygen-containing functional groups.

[Characterization of Cr Tolerance and Accumulation in Lolium perenne L. and Pharibitis purpurea(L.) Voigt].

Considering the serious pollution of heavy metal-chromium (Cr) in soil, there is an urgent need for effective selection of Cr-tolerant plant species. In order to gain fundamental insights into the tolerance and accumulation capabilities of Lolium perenne L. and Pharibitis purpurea(L.) Voigt under Cr stress, a pot experiment was conducted to investigate their growth, physiology and accumulation characteristics under Cr(Ⅲ) and Cr(Ⅵ) stress. The results showed the growth parameters could intuitively reflect the toxicity levels of Cr for plants. For instance, a low-level Cr(Ⅲ) (<250 mg·kg-1) in soil was good for plant growth as indicated by the significant elevation of plant height, root length and biomass in L. perenne (P<0.05). However, Cr(Ⅵ) at all concentrations (≥25 mg·kg-1) in the soil inhibited the growth of both plant species, and the root length was particularly sensitive to the toxicity of Cr. The physiological parameters of plant represented both the toxicity of Cr and the tolerance of plants under Cr stress. A decrease of root activity and an increase of malonaldehyde content were observed under Cr stress, which indicated the physiological metabolism of plants was disturbed. In the presence of both Cr species, the proline content increased, which served as an indicator for both high Cr toxicity and increase of osmotic balance in plants. A rise in SOD and POD activity reflected the defense ability of plants against oxidative stress caused by Cr. In addition, the Cr-accumulation related parameters were the major standards for tolerant species selection. The Cr(Ⅵ) accumulation capacities of both plant species were greater than their Cr(Ⅲ) accumulation capacities. The maximum accumulation amounts of L. perenne and P. purpurea reached 957.4 mg·kg-1 and 743.3 mg·kg-1 in roots and 394.7 mg·kg-1 and 340.4 mg·kg-1 in shoots, respectively. In comparison with P. purpurea, L. perenne displayed a stronger Cr accumulation capacity in roots with a maximum bioaccumulation factor of 15.55. However, the transport ability of P. purpurea was superior to L. perenne. All of the parameters demonstrated that both L. perenne and P. purpurea could be used as alternative plants for phytoremediation of Cr-contaminated soil.

MicroRNA-206 attenuates tumor proliferation and migration involving the downregulation of NOTCH3 in colorectal cancer.

Colorectal cancer (CRC) is the most common cancer diagnosed worldwide, and the development of metastases is a major cause of mortality. Accumulating evidence suggests that microRNAs are important in carcinogenesis by affecting the expression of genes that regulate cancer progression. A number of studies have shown that miR-206 is frequently downregulated in many human malignancies, including CRC, and is associated with a more malignant phenotype. Previous studies involving HeLa and C2C12 cells have validated the inhibitory mechanism of miR-206 via NOTCH3 targeting. However, whether or not the interplay between miR-206 and NOTCH3 also occurs in CRC is unknown. Therefore, we investigated the tumor suppressive and metastatic effects of miR-206 and its target, NOTCH3, in CRC. Based on the inverse association between the expression of miR-206 and NOTCH3 in CRC tissues, miR-206 mimics were transiently transfected into the SW480 (and its metastatic strain) and SW620 colon cancer cell lines. Upregulation of miR-206 inhibited cancer cell prolife-ration and migration, blocked the cell cycle, and activated apoptosis. The tumor suppressive capacity of miR-206 had a similar effect on CRC cells, although with a different metastatic potential, and may be explained by direct NOTCH3 signaling inhibition and indirect cross-talk with other signaling pathways involving CDH2 and MMP-9. These results support miR-206 as a tumor suppressor in CRC and suggest a potential therapeutic target for clinical intervention.

[The correlation between chemotherapeutic efficacy and breast cancer susceptibility gene 1 and class IIIß-tubulin protein expression in non-small cell lung cancer patients].

OBJECTIVE: To investigate the predictive value of breast cancer susceptibility gene 1 (BRCA1) and class IIIß-tubulin protein expression in tumor tissue for the efficacy of taxol and cisplatin combined chemotherapy (TP) in stage IIIB/IV non-small cell lung cancer (NSCLC) patients. METHODS: A total of 92 stage IIIB/IV NSCLC patients were recruited with 87 patients evaluated. Bronchoscopy or lung puncture tumor biopsy samples were obtained with BRCA1 and class IIIß-tubulin protein expression examined immunohistochemically before chemotherapy. The patients were randomly assigned to be received 4 to 6 cycles of TP chemotherapy regiments and followed up until death or lost. Response rate (RR), overall survival (OS) and time to tumor progression (TTP) were assessed. RESULTS: Among the 87 evaluated patients, the positive expression rates of BRCA1 and class IIIß-tubulin were 57.5% (50/87) and 48.3% (42/87) respectively. There was no significant difference in clinical characteristics among patients with different positive expression rate. According to different expression of BRCA1 and class IIIß-tubulin, the patients were divided into four groups: group A (low expression of both BRCA1 and class IIIß-tubulin), group B (high expression of both BRCA1 and class IIIß-tubulin), group C (high expression of only BRCA1) and group D (high expression of only class IIIß-tubulin). The RR was higher in group A than other three groups (60.7%, 34.8%, 9/19 and 6/17 respectively). The OS and TTP were longer in group A than other three groups [OS: (539.4 ± 17.6) days, (267.2 ± 20.5) days, (325.6 ± 24.1) days and (283.7 ± 26.2) days respectively; TTP: (256.9 ± 28.4) days, (143.8 ± 17.6) days, (179.3 ± 19.8) days and (152.6 ± 23.5) days respectively]. There were no significant differences among the other three groups. CONCLUSIONS: The expression level of BRCA1 and class IIIß-tubulin in tumor tissue is probably a predictor for the efficacy of TP chemotherapy in NSCLC patients. TP chemotherapy is more suitable for the NSCLC patients with lower expression of both BRCA1 and class IIIß-tubulin. Our study may provide a new sight for tailored chemotherapy in NSCLC patients.