IL-27 Alleviates Airway Inflammation and Airway Hyperresponsiveness in Asthmatic Mice by Targeting the CD39/ATP Axis of Dendritic Cells.

Interleukin-27 receptor (IL-27R) is expressed in a variety of immune cells and structural cells, including dendritic cells. The mechanism of IL-27 in asthma has not been fully elucidated. This study aimed to examine whether IL-27 regulated the CD39/ATP axis of dendritic cells in asthma. Our results showed that in ovalbumin (OVA)-induced asthma mouse model, IL-27Rα-/- asthmatic mice showed increased airway resistance, increased infiltration of inflammatory cells in lung tissue, proliferation of goblet cells, enhanced expression of Muc5 AC around airway epithelium, increased total number of cells and eosinophils, increased levels of total IgE, OVA-IgE, IL-4, IL-5, IL-13 and IL-17 A, and increased expression of transcription factors GATA-3 and RORγt in lung tissue. The expression of CD39 mRNA and protein in the lung tissue of IL-27Rα-/- asthmatic mice decreased, and the expression of NLRP3, ASC and Caspase-1 in NLRP3 inflammasome components increased. The concentration of ATP was significantly increased compared with WT asthmatic mice. In vitro experiments showed that the expression of CD39 in lung dendritic cells of IL-27Rα-/- asthmatic mice decreased, while the expression of NLRP3 inflammasome components NLRP3, ASC and Caspase-1 increased. These findings indicate that IL-27 directly and indirectly regulates immunoinflammatory responses in asthma by acting on dendritic cells CD39/ATP Axis.

ING5 overexpression upregulates miR-34c-5p/Snail1 to inhibit EMT and invasion of lung cancer cells.

ING5 belongs to the inhibitor of growth (ING) candidate tumor suppressor family, which is involved in multiple cellular functions, such as cell cycle regulation, apoptosis, and chromatin remodelling. Previously, we reported that ING5 overexpression inhibits EMT by regulating EMT-related molecules, including Snail1, at the mRNA and protein levels. However, the mechanisms remain unclear. In the current study, we identify that ING5 overexpression induces the upregulation of miR-34c-5p. The expression levels of both ING5 and miR-34c-5p in NSCLC tissues from the TCGA database are decreased compared with that in adjacent tissues. Higher expression levels of both ING5 and miR-34c-5p predict longer overall survival (OS). Snail1 is the target gene of miR-34c-5p, as predicted by an online database, which is further verified by a dual-luciferase reporter assay. The expression level of Snail1 in NSCLC cells is markedly reduced following miR-34c-5p overexpression, leading to the inactivation of the Snail1 downstream TGF-ß/Smad3 signaling pathway. The TGF-ß signaling-specific inhibitor LY2157299 reverses the enhanced EMT, proliferation, migration, and invasion abilities induced by the miR-34c-5p inhibitor. Furthermore, tail vein injection of miR-34c-5p agomir inhibits xenografted tumor metastasis. Overall, this study concludes that miR-34c-5p, induced by ING5 overexpression, is a tumor suppressor that targets Snail1 and mediates the inhibitory effects of ING5 on the EMT and invasion of NSCLC cells. These results provide a novel mechanism mediating the antitumor effects of ING5.

LOW DOSE OF ESMOLOL ATTENUATES SEPSIS-INDUCED IMMUNOSUPPRESSION VIA MODULATING T-LYMPHOCYTE APOPTOSIS AND DIFFERENTIATION.

ABSTRACT: Background: Immunosuppression caused by immune cell apoptosis and an imbalance of T helper 2 cells (T H 2) and T helper 1 cells (T H 1), is associated with poor outcomes in septic patients. Esmolol was reported to improve survival by modulating immune responses in septic shock. Whether esmolol could alleviate sepsis-induced immunosuppression and the optimal dose are unclear. Methods: Four hours after cecal ligation and puncture (CLP), Wistar rats were randomized into CLP, CLP + E-5 (esmolol: 5 mg·kg -1 ·h -1 ) and CLP + E-18 (esmolol: 18 mg·kg -1 ·h -1 ) groups. Eight rats were underwent sham operation. Eighteen hours after CLP, hemodynamics and organ histological injuries were evaluated, peripheral blood mononuclear cells apoptosis and T-lymphocyte subsets counts were determined by flow cytometry, and the expression of p-Akt, Bcl-2, cleaved Caspase-3, and p-Erk1/2 in splenic CD4 + T-lymphocytes was determined by western blot and immunohistochemistry. ß 1 -Adrenoreceptor expressions were evaluated using real-time polymerase chain reaction and immunohistochemistry. Results: Cecal ligation and puncture induced tachycardia, hypotension, hyperlactatemia, and multiple organ injury. Heart rate was unchanged in the CLP + E-5 group but decreased in the CLP + E-18 group. Hypotension, lactatemia, and multiple organ injuries were improved only in the CLP + E-5 group. T-lymphocyte apoptosis and T H 2/T H 1 ratio was decreased in CLP + E-5 but not in CLP + E-18. p-Akt and Bcl-2 expressions were increased, while cleaved Caspase-3 and p-Erk1/2 expressions were decreased in CLP + E-5. ß 1 -Adrenoreceptor expressions were unchanged in both CLP + E-5 and CLP + E-18 groups. Conclusions: Low dose of esmolol reduced T-lymphocyte apoptosis and restored T H 2/T H 1 ratio in septic shock. Esmolol might modulate Akt/Bcl-2/Caspase-3 pathway to relieve T-lymphocyte apoptosis and inhibit Erk1/2 activity to decrease T H 0 differentiation to T H 2. Esmolol may be a potential immunoregulator of septic shock.

Insights into the Interfacial Contact and Charge Transport of Gas-Sensing Liquid Metal Marbles.

Understanding the interfacial contacts between liquid metals and substrate materials is becoming increasingly important for the fast-rising liquid metal-enabled technologies. However, for such technologies, probing the contact behavior and interfacial charge transport has remained challenging due to the deformable nature of liquid metals and the presence of the surface oxide layer. Here, we encapsulate eutectic gallium indium (EGaIn) micro-/nanodroplets with tungsten trioxide (WO3) nanoparticles to form a WO3/EGaIn liquid metal marble network, in which the interfacial contact of the intrinsically semiconducting WO3 governs the charge transport. We investigate the interfacial structures and charge transport characteristics under different contact conditions and various gaseous environments. The results suggest that establishing a WO3/EGaIn heterostructure leads to near-ohmic contact behaviors and also the emergence of localized surface plasmon resonance. Density functional theory calculations of the WO3/EGaIn interface support the experiments by revealing atomistic attractions between EGaIn alloy and the O atoms from WO3, resulting in a Fermi level shift. We also show that the efficient interfacial charge transport of the liquid metal marble network results in an enhanced gas-sensing response. This work paves the way for the possibility of studying other liquid metal/semiconductor contacts for applications in soft electronics and optics.

Systemic injury caused by taurocholate-induced severe acute pancreatitis in rats.

Systemic injury plays a central role in severe acute pancreatitis (SAP). Retrograde biliopancreatic duct infusion of sodium taurocholate (NaT) is commonly used to establish SAP animal models. To better characterize the systemic injury in this model, SAP was induced in Sprague-Dawley rats by NaT administration (3.5 or 5%), followed by sacrifice at 3, 6, 9, 12, 24, 48 and 72 h. Normal saline was used as a control in Sham-operated rats. The mortality rate, ascites volume, and serum and ascitic fluid amylase and lipase activities were assessed. Multiple organ dysfunction, including dysfunction of the pancreas, lung, ileum, liver, and kidney, was investigated using hematoxylin and eosin staining. The interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α levels in the ascitic fluid, serum, and ileum tissues were evaluated using an enzyme-linked immunosorbent assay (ELISA). Tight junction proteins, zonula occludens-1 (ZO-1) and occludin, in ileum tissues were studied using immunofluorescence. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine (CRE) and urea levels were measured using an automatic biochemical analyzer. The results of the present study indicated that both 3.5 and 5% NaT could induce a stable elevation of pancreatitis indices, with histopathological injury of the pancreas, lungs and ileum (5% NaT). The ascitic fluid levels of IL-6 and IL-1ß were increased in the 5% NaT group. ALT and AST levels increased temporarily and recovered in 72 h, without a significant increase in CRE and urea levels or apparent hepatic and renal pathological injury. In conclusion, rats with NaT-induced SAP have characteristics of necrotizing hemorrhagic pancreatitis with multiple organ injuries, including inflammatory lung injury, ischemic intestinal injury and slight liver and kidney injuries.

Association between immunity and viral shedding duration in non-severe SARS-CoV-2 Omicron variant-infected patients.

Background: Coronavirus disease 2019 (COVID-19) is a respiratory-related disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). More than 200 countries worldwide are affected by this disease. The Omicron variant of SARS-CoV-2 is the major epidemic variant worldwide and is characterized by higher infectivity. However, the immunity and risk factors for prolonged viral elimination in patients with non-severe SARS-CoV-2 Omicron variant infections are unclear. Therefore, this study aimed to examine the relationship between immunity and duration of viral elimination in non-severe SARS-CoV-2 Omicron variant-infected patients in Shanghai. Methods: In total, 108 non-severe SARS-CoV-2 Omicron variant-infected patients from Shanghai New International Expo Center Fangcang Shelter Hospital were recruited in this study. They were further allocated to the early elimination (EE) and prolonged elimination (PE) groups according to SARS-CoV-2 nucleic acid positivity duration. Results: Compared to patients with EE, those with PE had increased serum concentrations of interleukin (IL)-5, IL-6, and IL-8; higher neutrophil count and neutrophil-to-lymphocyte ratio (NLR); lower lymphocyte, eosinophil, and red blood cell counts; and lower concentrations of hemoglobin and albumin (ALB). In lymphocyte subpopulation analysis, lower numbers of CD3+ T cells, CD4+ T cells, CD8+ T cells, and NK cells and a higher CD4/CD8 ratio were observed in patients with PE. In addition, correlation analysis results revealed that cycle threshold values of SARS-CoV-2 Omicron variant ORF1ab and N were negatively correlated with IL-6 and IL-8 levels and positively correlated with eosinophil count in patients with COVID-19. Finally, multivariate regression analysis showed that ALB, CD4/CD8 ratio, NLR, and eosinophil count were predictors of the SARS-CoV-2 Omicron variant elimination. Conclusion: In this study, we identified that the ALB, CD4/CD8 ratio, NLR, and eosinophil count were risk factors for prolonged viral elimination in non-severe SARS-CoV-2 Omicron variant-infected patients. These factors might be efficient indicators in the diagnosis, evaluation, and prognosis monitoring of the disease.

Chimeric RNA-binding protein-based killing switch targeting hepatocellular carcinoma cells.

Cancer cell-specific killing switches are synthetic circuits developed as an intelligent weapon to specifically eliminate malignant cells. RNA-delivered synthetic circuits provide safer means to control oncolytic functions, in which proteolysis-responding capsid-cNOT7 is developed to enable logic computation and modular design. Unfortunately, although circuits containing these capsid-cNOT7s exhibited good performance when introduced as replicons, in modified mRNA (modRNA) delivery, the performance was not quite as good. To improve this situation, alternative modules suitable for modRNA delivery need to be developed. An attractive option is RNA-binding protein (RBP)/riboswitches. In this study, RBPs were engineered by fusing with degron and cleavage sites. The compatibility of these chimeric RBPs with proteolysis-based sensing units were tested. Eight two-input logic gates and four three-input logic gates were implemented. After building this chimeric RBP-based system, we constructed a hepatocellular carcinoma (HCC) cell-specific killing circuit using two proteolysis-based sensing units, a two-input logic OR gate, and a leakproof apoptosis-inducing actuator, which distinguished HCC cells and induced apoptosis in a mixed IMR90-PLC/PRF/5 population.

Association of remnant cholesterol with chronic kidney disease in middle-aged and elderly Chinese: a population-based study.

AIMS: Limited data regarding the association between remnant cholesterol (RC) and chronic kidney disease (CKD), largely based on an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2 (low eGFR), have yielded inconsistent results, and no report has demonstrated the relationship of RC with CKD [defined as low eGFR and/or albuminuria (defined as urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/g)] in Chinese general middle-aged and elderly population. Hence, we aimed to investigate the association between RC and CKD in such population. METHODS: In total, 7356 Chinese participants aged ≥ 40 years were recruited from five regional communities in Luzhou city between May 2011 and December 2011. Fasting RC was calculated from the lipid profile measured by standard laboratory procedures. Multivariate logistic regression models were used to evaluate the possible association between RC and CKD. RESULTS: Participants in the highest quartile of RC had higher body mass index, systolic and diastolic blood pressure, total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), fasting and 2-h postload blood glucose, glycated hemoglobin A1C, prevalence of prediabetes, type 2 diabetes mellitus (T2DM), hypertension, CKD, albuminuria, low eGFR, and lower high-density lipoprotein cholesterol (HDL-C) and eGFR compared with those in the lowest quartile (all P for trend < 0.01). Multivariate logistic regression analysis demonstrated that the risk of CKD gradually increased across RC quartiles (P for trend < 0.01), and participants in the highest quartile of RC were at a significantly increased risk of prevalent CKD compared to those in the lowest quartile in total subjects (odds rate: 1.344, 95% confidence intervals 1.097-1.648, P < 0.01). In subgroup analysis, significant relation between RC level and increased risk of prevalent CKD was detected in women, subjects with overweight/obesity, non-prediabetes, hypertension, normal HDL-C, appropriate and high LDL-C, and without cardiovascular disease (CVD) events after multiple adjustments. CONCLUSIONS: Higher RC is independently associated with increased risk of prevalent CKD, and RC might serve as a new risk biomarker for CKD in a general middle-aged and elderly Chinese population, especially in women, subjects with overweight/obesity, non-prediabetes, hypertension, normal HDL-C, appropriate and high LDL-C, and without CVD events.

Engineering L7Ae for RNA-Only Delivery Kill Switch Targeting CMS2 Type Colorectal Cancer Cells.

The lack of specific-targeting therapy to precisely identify and kill malignant cells while sparing others is a great challenge in colorectal cancer (CRC) treatment. In the era of molecular classification of tumors, CRC has been grouped into four Consensus Molecular Subtypes. Accounting for 37% of all types, the CMS2 group (canonical type) shows distinguishing features: WNT and MYC signaling activation. In this study, we designed an RNA-only delivery kill switch to specifically eliminate CMS2 type CRC cells. The sensing and logic processing functions are integrated by the newly engineered L7Ae, which can not only detect the stability of ß-catenin protein and the presence of cytoplasm located Myc/Myc-nick, but also do logic computation. The circuit specifically eliminated HCT-116 cells while sparing other kinds of cells, showing a proof-of-principle approach to precisely target CMS2 type CRC.

Parents' Experiences of Having a Young Child With Acute Lymphoblastic Leukemia in China.

BACKGROUND: Understanding parents' experiences is a prerequisite to developing interventions that are sensitive to needs of children and families. In China, little is known about parental experiences of having a young child with acute lymphoblastic leukemia (ALL). This phenomenological study aimed to describe parental experiences of having a young child with ALL in China. METHOD: Ten parents, recruited in central China using purposive sampling, participated in face-to-face, in-depth interviews using Haase's adaptation of Colaizzi's phenomenological method. RESULTS: Five theme categories were identified: (a) The Cancer Diagnosis as a Terrible Disaster-The Sky is Falling, (b) Fighting the Beast, (c) Putting on a Happy Face and Other Coping Strategies, (d) Diagnosis Disclosure: If We Tell and How to Tell, and (e) Hope-Filled Expectations: Returning to Normal Life. CONCLUSION: Parents put their child's health as their top priority. They strive to manage uncertainty about prognosis and cope with enormous pressures caused by children's suffering, financial burden, and stigma. Parents also express their resilience and hope throughout their child's cancer journey. Support services to strengthen specific families' protective factors (i.e., family/community support, hope, and positive coping) are needed to foster resilience and quality of life. Health care professionals should systematically assess parents' needs, provide validated education materials, and implement tailored interventions across the cancer continuum. Public education and advocacy about cancer is also necessary to decrease cancer-related stigma, and provide financial aid and health care resources in pediatric oncology.

[The Clinical Value of PNI in Assessing the Prognosis of Small Cell Lung Cancer].

OBJECTIVE: To evaluate the clinical value of prognostic nutritional index (PNI) in assessing the prognosis of small cell lung cancer (SCLC) patients. METHODS: The clinical data of SCLC patients who were initial diagnosed by pathology and conformed to the conditions of this study from January 2017 to January 2018 were retrospectively collected. The PNI values were calculated and divided into high PNI and low PNI groups according to the median value. The potential prognostic factors for SCLC patients were analyzed. RESULTS: One hundred and five patients were divided into high-PNI and low-PNI groups according to the PNI median (48.68). The median survival time was 25.1 months and 14.2 months respectively. The one-year survival rates were 82.5% and 65.3% respectively and the two-year survival rates were 49.7% and 28.4% respectively, the differences were all statistically significant ( P<0.05). Univariate analysis showed that gender, ECOG PS score, clinical stage and PNI were correlated with overall survival (OS) ( P<0.05). Multivariate analysis showed that PNI (odds ratio ( OR)=0.331，95% confidence interval: 0.189-0.580) and gender ( OR=1.897，95% confidence interval: 1.051-3.423) were independent prognostic factors for SCLC patients. CONCLUSION: Low PNI patients generally symbolize poor prognosis, PNI calculation is simple and easy to obtain, worthy of clinical promotion.

The diagnostic challenges and clinical course of a myeloid/lymphoid neoplasm with eosinophilia and ZBTB20-JAK2 gene fusion presenting as B-lymphoblastic leukemia.

We report the diagnostic challenges and the clinical course of a patient with an extraordinary presentation of B-lymphoblastic leukemia (B-ALL) with eosinophilia. We identified a novel ZBTB20-JAK2 gene fusion as a chimeric RNA transcript using the Archer platform. This gene fusion from the same patient was recently identified by Peterson et al. (2019) at the genomic level using a different sequencing technology platform. The configuration of this gene fusion predicts the production of a kinase-activating JAK2 fusion protein, which would normally lead to a diagnosis of Philadelphia chromosome-like B-ALL (Ph-like B-ALL). However, the unusual presentation of eosinophilia led us to demonstrate the presence of this gene fusion in nonlymphoid hematopoietic cells by fluorescence in situ hybridization (FISH) studies with morphologic correlation. Therefore, we believe this disease, in fact, represents blast crisis arising from an underlying myeloid neoplasm with JAK2 rearrangements. This case illustrates the difficulty in differentiating Ph-like B-ALL and myeloid/lymphoid neoplasm with eosinophilia and gene rearrangements (MLN-EGR) in blast crisis. As currently defined, the diagnosis of MLN-EGR relies on the hematologic presentations and the identification of marker gene fusions (including PCM1-JAK2, ETV6-JAK2, and BCR-JAK2). However, these same gene fusions, when limited to B-lymphoblasts, also define Ph-like B-ALL. Yet, our case does not conform to either condition. Therefore, the assessment for lineage restriction of gene rearrangements to reflect the pathophysiologic difference between B-ALL and MLN-EGR in blast crisis is likely a more robust diagnostic approach and allows the inclusion of MLN-EGR with novel gene fusions.

Liquid Metal-Based Route for Synthesizing and Tuning Gas-Sensing Elements.

There is a strong demand for developing tunable and facile routes for synthesizing gas-sensitive semiconducting compounds. The concept of synthesizing micro- and nanoparticles of metallic compounds in a tunable process, which relies on liquid metals, is presented here. This is a liquid-based ultrasonication procedure within which additional metallic elements (In, Sn, and Zn) are incorporated into liquid Ga that is sonicated in a secondary solvent. We investigate liquid metal sonication in dimethyl sulfoxide (DMSO) and water to show their impact on the size, morphology, and crystal structure of the particulated products. The synthesized materials are annealed to investigate their responses to model reducing (H2) and oxidizing (NO2) gas species. The preparation process in DMSO gives rise to predominantly monoclinic Ga2O3 crystals which are favorable for gas sensing, while the emergence of rhombohedral Ga2O3 phases from the water sonication process led to inactive samples. The ease of tunability without hazardous precursors during the synthesis procedure is demonstrated. The route presented here can be uniquely employed for designing and engineering on-demand functional materials for sensing applications.

Programmable Synthetic Protein Circuits for the Identification and Suppression of Hepatocellular Carcinoma.

Precisely identifying and killing tumor cells are diligent pursuits in oncotherapy. Synthesized gene circuits have emerged as an intelligent weapon to solve these problems. Gene circuits based on post-transcriptional regulation enable a faster response than systems based on transcriptional regulation, which requires transcription and translation, showing superior safety. In this study, synthetic-promoter-free gene circuits possessing two control layers were constructed to improve the specific recognition of tumor cells. Using split-TEV, we designed and verified the basic control layer of protein-protein interaction (PPI) sensing. Another orthogonal control layer was built to sense specific proteins. Two layers were integrated to generate gene circuits sensing both PPI and specific proteins, forming 10 logic gates. To demonstrate the utility of this system, the circuit was engineered to sense alpha-fetoprotein (AFP) expression and the PPI between YAP and 14-3-3σ, the matching profile of hepatocellular carcinoma (HCC). Gene-circuit-loaded cells distinguished HCC from other cells and released therapeutic antibodies, exhibiting in vitro and in vivo therapeutic effects.

Identification of Cholangiocarcinoma Associated with Hepatolithiasis via the Combination of miRNA and Ultrasound.

BACKGROUND: Identification of cholangiocarcinoma (CCA) associated with hepatolithiasis (HL) is difficult. There is no effective method to discriminate CCA associated with HL (HL-CCA) from HL currently. OBJECTIVE: To explore the value of clinical data, ultrasonic characteristics and miRNA expression level in the identification of HL-CCA. METHODS: Thirty-one patients with HL-CCA in Huazhong University of Science and Technology Union Shenzhen Hospital were enrolled in the observation group, while 40 patients with HL alone were included in the control group. The clinical data, ultrasonic characteristics, and miRNA expression level of the two groups were recorded and analyzed to explore the potential indicators for the identification of HL-CCA. RESULTS: The accuracy of ultrasound in the diagnosis of HL-CCA was low (54.84%). Multivariate logistic regression analysis showed that liver abscess (P=0.021), indistinct border demarcation (P=0.015), non-homogenous echotexture (P=0.019), missed portal vein around lesion (P=0.032), miRNA-21 (P=0.018) and miRNA-221 (P=0.009) were the potential indicators for the identification of HL-CCA. The combined diagnosis based on logistic regression contained liver abscess, border demarcation, echotexture, portal vein around lesion, miRNA-21 and miRNA-221. The results showed that the accuracy of combined diagnosis identifying HL-CCA was the most accurate (AUC=0.911), which was significantly greater than the AUC of miRNA-21 or miRNA-221 individually (P<0.05), with a sensitivity and specificity of 77.42% and 97.50%, respectively. CONCLUSION: Patients with HL-CCA show high incidence of hepatic abscess and elevated miRNA-21 and miRNA-221 expression level. The ultrasonic features are more likely to show indistinct border demarcation, non-homogenous echotexture, and missed portal vein around lesion. The combined diagnosis is more accurate in the identification of HL-CCA.

p16 promotes proliferation in cervical carcinoma cells through CDK6-HuR-IL1A axis.

The Cyclin-Dependent Kinase Inhibitor p16 (p16) acts as a tumor suppressor in most cells, but for HPV transformed cervical cancer, in which oncoprotein E7 expressed by human papillomavirus (HPV) mediates the degradation of retinoblastoma protein (Rb), p16 exhibits oncogenic activity. Our study was conducted to study the mechanism underling p16 mediated promoting effect of cell proliferation in cervical cancer cell lines. CCK8 assay and EdU incorporation were conducted to evaluate cell proliferation. Loss-of-function assay was used to silence p16 in Ca Ski and SiHa cells. Next, western blot, qPCR, RNA silencing, luciferase activity assay, run-on assay, mRNA stability assay, RNA immunoprecipitation, co-immunoprecipitation Immunofluorescence were performed to examine the interaction between CDK6, HuR, and IL1A mRNA in p16 mediated proliferation promoting effect. Our results showed that: (1) Silencing p16 inhibited the proliferation of cervical cancer cells by decreasing the half-life of IL1A mRNA in CDK6 dependent manner; (2) The stabilization of IL1A mRNA was regulated by HuR which could be inactivated by p16/CDK6 mediated phosphorylation at Ser202; (3) IL1A mediated the oncogenic activity of p16 in cervical carcinoma cell lines. In conclusion, p16 promotes proliferation in cervical carcinoma cells through CDK6-HuR-IL1A axis.

Response gene to complement-32 promotes cell survival via the NF-κB pathway in non-small-cell lung cancer.

Response gene to complement (RGC)-32 regulates the cell cycle in response to complement activation. The present study demonstrated that the expression level of RGC-32 is higher in human non-small-cell lung cancer (NSCLC) tissues compared with health controls. Overexpressing RGC-32 induced p65 nucleus translocation, significantly increased nuclear p65 levels and promoted the proliferation of A549 cells. Knockdown of RGC-32 by short hairpin RNA decreased the expression level of nuclear p65 and inhibited cell proliferation. The increase in cell proliferation induced by RGC32 could be abolished by the NF-κB inhibitor pyrrolidine dithiocarbamate. Mechanistic studies indicated that RGC32 mediated NF-κB downstream genes, including vascular cell adhesion protein 1, interleukin-6, cyclin dependent kinase inhibitor 2C, testin and vascular endothelial growth factor A. In summary, the present study demonstrated a novel role of RGC-32 in the progression of NSCLC via the NF-κB pathway and p65. Therefore, RGC-32 could be a potential therapeutic target for NSCLC.

CD44 3'-Untranslated Region Functions as a Competing Endogenous RNA to Enhance NK Sensitivity of Liver Cancer Stem Cell by Regulating ULBP2 Expression.

Liver CSCs are a rare subpopulation of heterogenous liver cancer cells with self-renewal and differentiation properties, which has emerged as a promising therapeutic target. Compelling data shows that NK cells selectively eliminate human cancer derived CSCs like colorectal carcinoma, melanoma, and glioblastoma. But the effect of NK cells on liver CSCs still remains unknown. To study the cytotoxic effect of NK cells on liver CSCs and the mechanism, we performed cytotoxicity assay, ELISA assays, CRISPRi, qRT-PCR, immunoblotting, RNA immunoprecipitation, and luciferase reporter using two types of CSCs reprogrammed from HCC. CSCs derived from liver cancer were susceptible to NK cell mediated cytotoxicity. The susceptibility of liver CSCs to NK cell-mediated cytotoxicity declined significantly after silencing CD44 by CRISPRi-mediated gene knockdown. CD44 3' UTR functioned as a ceRNA to regulate the expression of ULBP2 mainly by competing miR-34a. CD44 3' UTR functioned as a ceRNA to enhance NK sensitivity of liver cancer stem cell by regulating ULBP2 expression.

LINC00702 suppresses proliferation and invasion in non-small cell lung cancer through regulating miR-510/PTEN axis.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been consistently reported to be involved in the progression of non-small cell lung cancer (NSCLC). In this study, we aimed to identify aberrantly expressed lncRNAs in NSCLC, in order to explore new therapeutic targets for NSCLC. METHODS: Two pairs of NSCLC and adjacent normal tissues were first analyzed by RNA sequencing. The expressions of LINC00702 in 40 pairs patient samples and in 4 NSCLC cell lines was measured by quantitative real-time PCR. Putative target miRNAs of LINC00702 were predicted by the bioinformatics tools. The effect of LINC00702 on tumor growth in vivo was evaluated. RESULTS: LINC00702 was significantly down-regulated in patients with NSCLC, which was correlated with tumor size and metastasis. In addition, overexpression of LINC00702 markedly suppressed proliferation and metastasis in NSCLC cells via inducing apoptosis in vitro and in vivo. Moreover, bioinformatics and luciferase reporter assays demonstrated that LINC00702 functioned as a competing endogenous RNA (ceRNA) for miR-510 in NSCLC, and upregulated its target gene PTEN. CONCLUSION: Our results indicated that LINC00702 modulated the expression of PTEN gene by acting as a ceRNA for miR-510 in NSCLC. Therefore, LINC00702 may serve as a potential target for the diagnosis and treatment of patients with NSCLC.

IL-27 inhibits non-small-cell lung cancer cell metastasis by miR-935 in vitro.

INTRODUCTION: Non-small-cell lung cancer (NSCLC) accounts for more than half of all lung cancer cases. Cytokines play an important role in NSCLC, including IL-27. IL-27 inhibits NSCLC progression; however, the mechanism is not clear. The purpose of this study is to investigate the effects of IL-27 on NSCLC cell proliferation and metastasis. MATERIALS AND METHODS: NSCLC cells were treated with IL-27 or transfected with miR-935, and the cell proliferation was assayed by Cell Counting Kit-8 (CCK-8) and colony formation. Cell metastasis was analyzed by Transwell chamber system and wound healing assay. IL-27 protein in the medium was analyzed by ELISA. IL-27 mRNA expression was measured by quantitative reverse transcriptase-PCR. RESULTS: We found that IL-27 played an inhibiting role in NSCLC cell proliferation and metastasis. The molecular mechanism of the suppressing role of IL-27 in NSCLC was regulated by miR-935. IL-27 expression was negatively associated with miR-935 in the clinical NSCLC samples. CONCLUSION: The study revealed that IL-27 decreased lung cancer cell proliferation and metastasis via miR-935.