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Circular RNAs (circRNAs) are a type of endogenous noncoding RNA which have been verified to participate in numerous pathophysiological processes. However, the underlying role of circRNAs in osteosarcoma tissue is still unidentified. Our study aims to investigate the circRNA expression profiles in osteosarcoma tissue and investigate the physiological functions of circRNAs. Human circRNAs microarray analysis showed that 785 differently expressed circRNAs were distinguished in osteosarcoma tissue and adjacent non-tumor tissue with 2 fold change. Circ-NT5C2 was validated to be up-regulated expressed in 52 pairs of osteosarcoma tissue and cell lines. Furthermore, the enforced expression of circ-NT5C2 could act as a valuable diagnostic marker for osteosarcoma detection with AUC (area under the ROC curve) value of 0.753. Functional validation experiments verified that circ-NT5C2 silencing suppressed the proliferation and invasion, and promoted apoptosis of osteosarcoma cells in vitro. In vivo, circ-NT5C2 silencing inhibited the tumor growth. Bioinformatics analysis and rescue experiments indicated that circ-NT5C2 sponged miR-448, which was confirmed by luciferase reporter assay and RT-PCR assay. Overall, our study investigates the circRNAs expression profiles and determines the function of circ-NT5C2 in osteosarcoma tumorigenesis, which might serve as a novel therapeutic target of osteosarcoma patients.

IntroductionMicroRNA-155 (miR-155) is an oncogenic microRNA, which is upregulated in many human cancers including colorectal cancer (CRC). Overexpression of miR-155 has been found to regulate several cancer-related pathways, and therefore, targeting miR-155 may be an effective strategy for cancer therapy. However, effective and safe delivery of anti-miR-155 to tumors remains challenging for the clinical applications of anti-miR-155-based therapeutics.MethodsIn this study, we explored the expression of miR-155 and the transcription factor nuclear factor kappa B (NF-κB) in CRC tissues and cell lines, and the possible relationship between miR-155 and NF-κB. We further report on anti-miR-155-loaded mesoporous silica nanoparticles (MSNs) modified with polymerized dopamine (PDA) and AS1411 aptamer (MSNs-anti-miR-155@PDA-Apt) for the targeted treatment of CRC.ResultsResults showed that miR-155 is overexpressed in CRC tissues and cell lines, and there is a positive feedback loop between NF-κB and miR-155. Compared to the control groups, MSNs-anti-miR-155@PDA-Apt could efficiently downregulate miR-155 expression in SW480 cells and achieve significantly high targeting efficiency and enhanced therapeutic effects in both in vivo and in vitro experiments. Furthermore, inhibition of miR-155 by MSNs-anti-miR-155@PDA-Apt can enhance the sensitivity of SW480 to 5-fluorouracil chemotherapy.ConclusionThus, our results suggested that MSNs-anti-miR-155@PDA-Apt is a promising nanoformulation for CRC treatment.

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Lung adenocarcinoma is the most prevalent type of lung cancer with a high incidence and mortality worldwide. Metastasis is the major cause of high death rate in lung cancer and the potential mechanism of lung adenocarcinoma metastasis remains indistinct. Emerging investigations have demonstrated that long noncoding RNA is a kind of non–protein coding RNA and plays a critical role in cancer progression and metastasis. TTN antisense RNA 1 (TTN‐AS1) has been reported to promote cell growth and metastasis in cancer. However, the function of TTN‐AS1 in lung adenocarcinoma is still to be illustrated. In this study, we observed that TTN‐AS1 was upregulated in tissues and cells of lung adenocarcinoma and associated with poor overall survival. TTN‐AS1 promoted cell proliferation, migration, invasion, and epithelial‐mesenchymal transition in lung cancer. TTN‐AS1 directly bound with miR‐4677‐3p and negatively regulated miR‐4677‐3p. MiR‐4677‐3p rescued the inhibitive impacts of TTN‐AS1 knockdown on lung adenocarcinoma. Furthermore, zinc finger E‐box binding homeobox 1 (ZEB1) was the target of miR‐4677‐3p, and TTN‐AS1 modulated ZEB1 by competing for miR‐4677‐3p. TTN‐AS1 drove the invasion and migration of lung adenocarcinoma cells by targeting the miR‐4677‐3p/ZEB1 axis. To sum up, our study offers insights into the mechanism of TTN‐AS1 in lung adenocarcinoma metastasis and targeting the TTN‐AS1/miR‐4677‐3p/ZEB1 axis may be the potential innovate therapeutic strategy for the patients with lung adenocarcinoma.

Uridine phosphorylase 1 (UPP1) has been reported as an oncogene in several malignancies. In glioma, the role of UPP1 remains unclear. This study was performed to explore its role in glioma at transcriptional level. Totally, 998 glioma patients with clinical data were enrolled, including 301 mRNA microarray data from Chinese Glioma Genome Atlas (CGGA) dataset and 697 RNAseq data from The Cancer Genome Atlas (TCGA) dataset. Statistical analysis was performed with R language. UPP1 expression level was positively correlated with WHO grade of glioma. UPP1 was significantly upregulated in mesenchymal subtype and could serve as a potential biomarker for this subtype. Based on most correlated genes of UPP1, Gene ontology analysis revealed that UPP1 was profoundly associated with immune and inflammatory response. Gene Sets Variation Analysis was further performed and showed that UPP1 was particularly correlated with MHC‐II and LCK, which were mainly associated with activities of antigen‐presenting cells and T cells. Moreover, UPP1 was found to be synergistic with various immune checkpoint members, especially with PD1 pathway and B7‐H3. Finally, Kaplan‐Meier curves revealed that higher UPP1 indicated significantly shorter survival for glioma patients. Taken together, UPP1 played an oncogenic role in glioma via suppressing tumor‐related immune response.

Early identification of infection severity and organ dysfunction is crucial in improving outcomes of patients with sepsis. We aimed to develop a new combination of blood-based biomarkers that can early predict 28-day mortality in patients with sepsis or septic shock. We enrolled 66 patients with sepsis or septic shock and compared 14 blood-based biomarkers in the first 24 h after ICU admission. The serum levels of interleukin-6 (IL-6) (median 217.6 vs. 4809.0 pg/ml, P = 0.001), lactate (median 2.4 vs. 6.3 mmol/L, P = 0.014), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (median 1596.5 vs. 32,905.3 ng/ml, P < 0.001), prothrombin time (PT) (median 15.6 vs. 20.1 s, P = 0.030), activated partial thrombin time (APTT) (median 45.1 vs. 59.0 s, P = 0.026), and international normalized ratio (INR) (median 1.3 vs. 1.8, P < 0.001) were significantly lower in the survivor group. IL-6, NT-proBNP, and INR provided the best individual performance in predicting 28-day mortality of patients with sepsis or septic shock. Furthermore, the combination of these three biomarkers achieved better predictive performance (AUC 0.890, P < 0.001) than conventional scoring systems. In summary, the combination of IL-6, NT-proBNP, and INR may serve as a potential predictor of 28-day mortality in critically ill patients with sepsis or septic shock.

Liposarcoma is a common subtype of soft tissue sarcoma and accounts for 20% of all sarcomas. Conventional chemotherapeutic agents have limited efficacy in liposarcoma patients. Expression and activation of serine/threonine-protein kinase dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1B (DYRK1B) is associated with growth and survival of many types of cancer cells. However, the role of DYRK1B in liposarcoma remains unknown. In this study, we investigated the functional and therapeutic relevance of DYRK1B in liposarcoma. Tissue microarray and immunohistochemistry analysis showed that higher expression levels of DYRK1B correlated with a worse prognosis. RNA interference-mediated knockdown of DYRK1B or targeting DYRK1B with the kinase inhibitor AZ191 inhibited liposarcoma cell growth, decreased cell motility, and induced apoptosis. Moreover, combined AZ191 with doxorubicin demonstrated an increased anti-cancer effect on liposarcoma cells. These findings suggest that DYRK1B is critical for the growth of liposarcoma cells. Targeting DYRK1B provides a new rationale for treatment of liposarcoma.