Structural insights into the Langya virus attachment glycoprotein.

Langya virus (LayV) was recently detected in patients with acute pneumonic diseases in China. Genome alignment indicated that LayV is a type of zoonotic henipavirus (HNV) that might also infect domestic animals. Previous studies revealed that HNVs mainly use ephrin-B1, ephrin-B2, or ephrin-B3 as cell receptors and the attachment glycoprotein (G) is the host cell receptor-binding protein. However, the LayV receptor remains unknown. Here, we present the 2.77 Å crystal structure of the LayV G C-terminal domain (CTD). We show that the LayV G protein CTD possesses a similar architecture as the Mojiang virus (MojV) G protein but is markedly different from the Nipah virus (NiV), Hendra virus (HeV), and Cedar virus (CedV) G proteins. Surface plasmon resonance (SPR) experiments indicate that LayV G does not bind ephrin-B proteins. Steric hindrance may prevent interactions between LayV G and ephrin-B. Our data might facilitate drug development targeting LayV.

Highly Optically Selective and Thermally Insulating Porous Calcium Silicate Composite SiO2 Aerogel Coating for Daytime Radiative Cooling.

Daytime radiative cooling technology offers a low-carbon, environmentally friendly, and nonpower-consuming approach to realize building energy conservation. It is important to design materials with high solar reflectivity and high infrared emissivity in atmospheric windows. Herein, a porous calcium silicate composite SiO2 aerogel water-borne coating with strong passive radiative cooling and high thermal insulation properties is proposed, which shows an exceptional solar reflectance of 94%, high sky window emissivity of 96%, and 0.0854 W/m·K thermal conductivity. On the SiO2/CaSiO3 radiative cooling coating (SiO2-CS-coating), a strategy is proposed to enhance the atmospheric window emissivity by lattice resonance, which is attributed to the eight-membered ring structure of porous calcium silicate, thereby increasing the atmospheric window emissivity. In the daytime test (solar irradiance 900W/m2, ambient temperature 43 °C, wind speed 0.53 m/s, humidity 25%), the temperature inside the box can achieve a cooling temperature of 13 °C lower than that of the environment, which is 30 °C, and the theoretical cooling power is 96 W/m2. Compared with the commercial white coating, SiO2-CS-coating can save 70 kW·h of electric energy in 1 month, and the energy consumption is reduced by 36%. The work provides a scalable, widely applicable radiative-cooling coating for building comfort, which can greatly reduce indoor temperatures and is suitable for building surfaces.

Traditional Banxia Xiexin decoction inhibits invasion, metastasis, and epithelial mesenchymal transition in gastric cancer by reducing lncRNA TUC338 expression.

Background: Banxia Xiexin decoction (BXD) is a classic traditional Chinese medicine (TCM) formula clinically used to treat chronic gastritis, gastric ulcers, gastric cancer, and many other gastrointestinal diseases. Long noncoding RNAs (lncRNAs) have been shown to play an important role in maintaining the malignant phenotype of tumors. However, no relevant studies have shown whether Banxia Xiexin decoction regulates and controls lncRNA TUC338, and the effect of TUC338 on the regulation of gastric cancer invasion and metastasis remains unclear. Purpose: To investigate the ability of the traditional Chinese medicine (TCM) Banxia Xiexin decoction (BXD) to inhibit the migration and invasion of human gastric cancer AGS cells by regulating the long noncoding RNA (lncRNA) TUC338. Methods: UHPLC‒MS/MS was used to analyze the chemical components of BXD. MTT was performed to determine the effects of BXD on the proliferation of AGS cells. qRT‒PCR was used to determine the expression of lncRNA TUC338 in gastric cancer tissues, paracarcinoma tissues, AGS human gastric cancer cells and GES-1 normal gastric mucosa cells and to evaluate the effects of BXD on the expression of lncRNA TUC338 in AGS cells. Lentiviral transfection was used to establish human gastric cancer AGS cells with knocked down lncRNA TUC338 expression. The effects of lncRNA TUC338 knockdown on the migration and invasion of AGS cells were observed by a scratch assay and Transwell migration assay, respectively. Western blotting was performed to analyze the effects of lncRNA TUC338 knockdown on epithelial-to-mesenchymal transition (EMT) in AGS cells. We performed quality control on three batches of BXD. We used UHPLC‒MS/MS to control the quality of three random batches of BXD used throughout the study. Results: Ninety-five chemical components were identified from the water extract of BXD, some of which have anticancer effects. The expression of TUC.338 in gastric cancer tissues was higher than that in para-carcinoma tissues. BXD inhibited the invasion and migration of gastric cancer cells by inhibiting the expression of lncRNA TUC338, which reduced EMT. After knockdown of lncRNA TUC338, the migration and invasion of AGS cells were reduced; the expression of the EMT-related protein E-cadherin was increased, and the expression of N-cadherin and vimentin was reduced. Conclusions: The present results suggest that BXD has potential as an effective treatment for gastric cancer through the inhibition of lncRNA TUC338 expression.

Effect of acute hypervolemic hemodilution with bicarbonated Ringer's solution on perioperative S100ß and NSE in elderly patients undergoing spine surgery.

To explore the effect of acute hypervolemic hemodilution (AHH) with bicarbonated Ringer's solution (BRS) on perioperative serum S100ß protein (S100ß) and neuron-specific enolase (NSE) in elderly patients undergoing spine surgery. Ninety patients with lumbar spondylolisthesis and fracture surgery admitted to our hospital from January 2022 to August 2022 were selected as the study subjects, and they were randomly and equally divided into group H1 (AHH with BRS), group H2 (AHH with lactated Ringer's solution) and group C (no hemodilution). The serum contents of S100ß and NSE of the three groups at different times were evaluated. There were significant differences in the incidence of postoperative cognitive dysfunction (POCD) among the three groups at T1 and T2 (P < 0.05). There were obvious differences in the contents of S100ß and NSE among the three groups at T1 and T2 (P < 0.001), with no overt difference in the incidence of perioperative complications among the three groups (P > 0.05). The use of AHH with BRS can effectively reduce the effect on cognitive function in the elderly with spine surgery, which greatly reduces the nervous system injury, and has certain application value in clinic.

SARS-CoV-2 Nsp8 induces mitophagy by damaging mitochondria.

Autophagy plays an important role in the interaction between viruses and host cells. SARS-CoV-2 infection can disrupt the autophagy process in target cells. However, the precise molecular mechanism is still unknown. In this study, we discovered that the Nsp8 of SARS-CoV-2 could cause an increasing accumulation of autophagosomes by preventing the fusion of autophagosomes and lysosomes. From further investigation, we found that Nsp8 was present on mitochondria and can damage mitochondria to initiate mitophagy. The results of experiments with immunofluorescence revealed that Nsp8 induced incomplete mitophagy. Moreover, both domains of Nsp8 orchestrated their function during Nsp8-induced mitophagy, in which the N-terminal domain colocalized with mitochondria and the C-terminal domain induced auto/mitophagy. This novel finding expands our understanding of the function of Nsp8 in promoting mitochondrial damage and inducing incomplete mitophagy, which helps us to understand the etiology of COVID-19 as well as open up new pathways for creating SARS-CoV-2 treatment methods.

Two Resveratrol Oligomers Inhibit Cathepsin L Activity to Suppress SARS-CoV-2 Entry.

Cell entry of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) depends on specific host cell proteases, which are the key targets for preventing and treating viral infections. Herein, we describe miyabenol C and trans-ε-viniferin, two resveratrol oligomers that specifically inhibit SARS-CoV-2 entry by targeting host protease cathepsin L. Several cell-based assays were used to demonstrate the effect of resveratrol oligomers, and their target was identified via screening of antiviral targets. Molecular docking analysis suggested that the oligomers could occupy the active cavity of cathepsin L. The surface plasmon resonance assay showed that the equilibrium dissociation constant (KD) values of miyabenol C-cathepsin L and trans-ε-viniferin-cathepsin L were 5.54 and 8.54 µM, respectively, indicating their excellent binding ability for cathepsin L. Our study demonstrated the potential application of resveratrol oligomers as lead compounds in controlling SARS-CoV-2 infection by targeting cathepsin L.

Cytochrome P450 Omega-Hydroxylase 4a14 Attenuates Cholestatic Liver Fibrosis.

BACKGROUND: Cholestasis is a pathological condition involving obstruction of bile secretion and excretion that results in hepatotoxicity, inflammation, fibrosis, cirrhosis, and eventually liver failure. Common bile duct ligation (BDL) model is a well-established murine model to mimic cholestatic liver fibrosis. We previously reported that cytochrome P450 omega-hydroxylase 4a14 (Cyp4a14) plays an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD)-related fibrosis. The goal of this study was to determine the role of Cyp4a14 in cholestatic-induced liver fibrosis. METHODS: C57BL/6 mice were subjected to BDL for 14 days, and Cyp4a14 mRNA and protein levels were examined and compared with those of the sham group. Cyp4a14 knockout mice and adeno-associated virus (AAV)-mediated overexpression of Cyp4a14 in C57BL/6 mice underwent BDL and liver histology, and key fibrosis markers were examined. RESULTS: Both hepatic Cyp4a14 mRNA and protein levels were markedly reduced in BDL liver compared with the time-matched sham group. Cyp4a14 gene-deficient mice aggravates whereas its overexpression alleviates BDL-induced hepatic fibrosis, which were determined by liver function, liver histology, and levels of key fibrotic markers including α-smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1), and collagen 1a2 (Col1a2). CONCLUSION: Cyp4a14 exerts a contrasting role in different hepatic fibrosis models. Strategies that enhance Cyp4a14 activity may be potential strategies to cholestatic related liver fibrosis.

Esophageal carcinoma cell-excreted exosomal uc.189 promotes lymphatic metastasis.

Most cancers are old age-related diseases. Patients with lymphatic metastasis have an extremely poor prognosis in esophageal cancers (ECs). Previous studies showed ultraconserved RNAs are involved in tumorigenesis and ultraconserved RNA 189 (uc.189) served as an oncogene in cervical cancer, but the effect of exosomal uc.189 in esophageal squamous cell carcinoma (ESCC) remains undefined. This study revealed that uc.189 is closely correlated with lymph node (LN) metastasis and the number of lymphatic vessels in ESCC. ESCC-secreted exosomal uc.189 is transferred into human lymphatic endothelial cells (HLECs) to promote its proliferation, migration and tube formation to facilitate lymph node metastasis. Mechanistically, uc.189 regulated EPHA2 expression by directly binding to its 3'UTR region through dual-luciferase reporter assay. Over-expression and knockdown of EPHA2 could respectively rescue and simulate the effects induced by exosomal uc.189. Especially, the uc.189-EPHA2 axis activates the P38MAPK/VEGF-C pathway in HLECs. Finally, ESCC-secreted exosomal of uc.189 promotes HLECs sprouting in vitro, migration, and lymphangiogenesis. Thus, these findings suggested that exosomal uc.189 targets the EPHA2 of HLECs to promote lymphangiogenesis, and may represent a novel marker of diagnosis and treatment for ESCC patients in early stages.

Land-Surface Diurnal Effects on the Asymmetric Structures of a Postlandfall Tropical Storm.

After a tropical storm makes landfall, its vortex interacts with the surrounding environment and the underlying surface. It is expected that diurnal variation over land will affect storm structures. However, this has not yet been explored in previous studies. In this paper, numerical simulation of postlandfall Tropical Storm Bill (2015) is conducted using a research version of the NCEP Hurricane Weather Research and Forecasting (HWRF) model. Results indicate that during the storm's interaction with midlatitude westerlies over the Great Plains, the simulated storm with the SLAB land-surface scheme is stronger, with faster eastward movement and attenuation, and more asymmetric structures than that with the NOAH land-surface scheme. More symmetric structures correspond with a slower weakening and slower eastward movement of the storm over land. Further diagnoses suggest an obvious response of the storm's asymmetric structures to diurnal effects over land. Surface diabatic heating in the storm environment is important for the storm's symmetric structures and intensity over land. Specifically, during the transition from nighttime to daytime, the evident strengthening of convective instability, atmospheric baroclinicity, and the lateral advection of high θ e air in the storm environment, associated with the rapid increase in surface diabatic heating, are conducive to the development of vertical vorticity and storm-relative helicity, thus contributing to the maintenance of the storm's symmetric structures and intensity after landfall.

piR-19166 inhibits migration and metastasis through CTTN/MMPs pathway in prostate carcinoma.

Tumor metastasis is one of death causes for patients of prostate carcinoma. PIWI-interacting RNAs (piRNAs) are a subtype of noncoding protein RNAs that are involved in tumorigenesis, but the effect of piRNAs in prostate carcinoma (PCa) remains unclear. This article showed the identification of piRNAs was performed using a piRNA microarray screen in PCa tissues and several piRNAs were identified as dysregulated. The two up-regulated piRNAs (piR-19004 and piR-2878) and one down-regulated piR-19166 have been validated in the tissues and cell lines of PCa using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Further studies showed that piR-19166 is transfected into PCa cells to suppress its migration and metastasis. Mechanistically, cortactin (CTTN) 3' untranslated region (UTR) was complementary combined with piR-19166 by bioinformatic prediction and identified as a direct target of piR-19166 through dual-luciferase reporter assay. Over-expression and knockdown of CTTN could respectively rescue and simulate the effects induced by piR-19166. Finally, piR-19166 suppresses migration and metastasis by the CTTN/matrix metalloproteinases (MMPs) pathway in PCa cells. Thus, these findings suggested that piR-19166 targets the CTTN of prostate cancer cells to inhibit migration and distant metastasis, and may represent a new marker of diagnosis and treatment for PCa patients in early stages.

Changes in Cartilage and Subchondral Bone of Femoral Trochlear Groove After Patellectomy in Growing Rabbits.

OBJECTIVE: To explore the effects of patellectomy on the bony and cartilaginous morphology of the trochlear groove in growing rabbits. METHODS: Forty-eight 4-week-old New Zealand white rabbits were randomly assigned to two groups. The control group underwent a sham surgical procedure, whereas the patellectomy group underwent patella excision surgery. Half of the rabbits in each group were sacrificed 3 months postoperatively; the rest were sacrificed 6 months postoperatively. Hematoxylin and eosin staining was performed on collected samples. Measurements included the bony and cartilaginous sulcus angles of the trochlear groove. In addition, the thickness of the articular cartilage at the deepest sulcus position (central thickness) and at the mid-position of the medial and lateral facets was measured and compared between groups. RESULTS: Three months after surgery, histological images revealed significant differences between the control group and the patellectomy group in cartilaginous sulcus angle (144.2° ± 1.5° vs 151.9° ± 2.4°, respectively; P < 0.001). No obvious difference in bony sulcus angle was found between the groups. Six months after surgery, significant between-group differences were observed in cartilaginous sulcus angle (136.3° ± 2.5° in control group vs 160.7° ± 3.0° in patellectomy group, P < 0.001) and bony sulcus angle (136.2° ± 2.2° in control group vs 160.4° ± 2.6° in patellectomy group, P < 0.001). However, there were no significant intra-group differences between cartilaginous and bony sulcus angles in either group. Three months after surgery, significant between-group differences were detected in articular cartilage thickness at the three different positions (medial facet: 324.3 ± 14.0 µm in control group vs 391.7 ± 98.8 µm in patellectomy group, P = 0.029; central position: 362.1 ± 13.6 µm in control group vs 730.3 ± 76.8 µm in patellectomy group, P < 0.001; lateral facet: 324.6 ± 12.7 µm in control group vs 358.5 ± 38.7 µm in patellectomy group, P = 0.009). No between-group differences in cartilage thickness were found at 6 months. CONCLUSIONS: Abnormal mechanical stress (patellectomy) during a rabbit's development can cause flattening of the femoral trochlear cartilage, followed by changes in the subchondral osseous layer. Abnormal mechanical stress is a crucial factor in the development of trochlear groove dysplasia.

Land-surface processes and summer-cloud-precipitation characteristics in the Tibetan Plateau and their effects on downstream weather: a review and perspective.

Correct understanding of the land-surface processes and cloud-precipitation processes in the Tibetan Plateau (TP) is an important prerequisite for the study and forecast of the downstream activities of weather systems and one of the key points for understanding the global atmospheric movement. In order to show the achievements that have been made, this paper reviews the progress on the observations for the atmospheric boundary layer, land-surface heat fluxes, cloud-precipitation distributions and vertical structures by using ground- and space-based multiplatform, multisensor instruments and the effect of the cloud system in the TP on the downstream weather. The results show that the form drag related to the topography, land-atmosphere momentum and scalar fluxes is an important part of the parameterization process. The sensible heat flux decreased especially in the central and northern TP caused by the decrease in wind speeds and the differences in the ground-air temperatures. Observations show that the cloud and precipitation over the TP have a strong diurnal variation. Studies also show the compressed-air column in the troposphere by the higher-altitude terrain of the TP makes particles inside clouds vary at a shorter distance in the vertical direction than those in the non-plateau area so that precipitation intensity over the TP is usually small with short duration, and the vertical structure of the convective precipitation over the TP is obviously different from that in other regions. In addition, the influence of the TP on severe weather downstream is preliminarily understood from the mechanism. It is necessary to use model simulations and observation techniques to reveal the difference between cloud precipitation in the TP and non-plateau areas in order to understand the cloud microphysical parameters over the TP and the processes of the land boundary layer affecting cloud, precipitation and weather in the downstream regions.

Effects of etanercept and infliximab on bone metabolism indexes in patients with ankylosing spondylitis.

Effect of etanercept and infliximab on bone metabolism indexes in patients with ankylosing spondylitis (AS) were evaluated. The clinical data of 80 patients with ankylosing spondylitis admitted to Affiliated Hospital of Hebei University of Engineering from June 2015 to March 2016 were selected. There were 39 patients treated with Enbrel as Enbrel group and 41 patients treated with Infliximab as Infliximab group. The general data of the two groups of patients were collected and various indexes before and 12 and 24 weeks after treatment were recorded. Adverse reactions of the two groups of patients after treatment were recorded and the clinical efficacy of the drugs was evaluated. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels in both groups decreased significantly before and 12 and 24 weeks after treatment (P<0.05), and 24 weeks after treatment showed a downward trend compared with 12 weeks (P<0.05). The ß-collagen special sequence (ß-CTX) level in the two groups was significantly lower after treatment than before (P<0.0001). The adverse reaction rate of Infliximab group (21.95%) was higher than that of Enbrel group (5.13%) (P>0.05). The morning stiffness time, BASDAI and BASFI indexes of the two groups of patients after treatment were significantly lower than those before treatment (P<0.0001). Schober test was significantly higher than that before treatment (P<0.0001); BASDAI in Infliximab group was lower than that in etanercept group (P<0.05). Both etanercept and infliximab have good therapeutic effects on AS, which can reduce the bone metabolism level of ß-CTX in AS patients and effectively improve the symptoms of affected medullary joints. The short-term efficacy of the two groups of patients is similar, but the incidence of adverse reactions of etanercept is slightly lower than that of infliximab.

Most of the Northern Hemisphere Permafrost Remains under Climate Change.

Degradation of cryospheric components such as arctic sea ice and permafrost may pose a threat to the Earth's climate system. A rise of 2 °C above pre-industrial global surface temperature is considered to be a risk-level threshold. This study investigates the impacts of global temperature rises of 1.5 °C and 2 °C on the extent of the permafrost in the Northern Hemisphere (NH), based on the 17 models of Coupled Model Intercomparison Project Phase 5 (CMIP5). Results show that, when global surface temperature rises by 1.5 °C, the average permafrost extent projected under Representative Concentration Pathway (RCP) scenarios would decrease by 23.58% for RCP2.6 (2027-2036), 24.1% for RCP4.5 (2026-2035) and 25.55% for RCP8.5 (2023-2032). However, uncertainty in the results persists because of distinct discrepancies among the models. When the global surface temperature rises by 2 °C, about one-third of the permafrost would disappear; in other words, most of the NH permafrost would still remain even in the RCP8.5 (2037-2046) scenario. The results of the study highlight that the NH permafrost might be able to stably exist owing to its relatively slow degradation. This outlook gives reason for hope for future maintenance and balance of the cryosphere and climate systems.

uc.454 Inhibited Growth by Targeting Heat Shock Protein Family A Member 12B in Non-Small-Cell Lung Cancer.

Transcribed ultraconserved regions (T-UCRs) classified as long non-coding RNAs (Lnc-RNAs) are transcripts longer than 200-nt RNA with no protein-coding capacity. Previous studies showed that T-UCRs serve as novel oncogenes, or tumor suppressors are involved in tumorigenesis and cancer progressive. Nevertheless, the clinicopathologic significance and regulatory mechanism of T-UCRs in lung cancer (LC) remain largely unknown. We found that uc.454 was downregulated in both non-small-cell LC (NSCLC) tissues and LC cell lines, and the downregulated uc.454 is associated with tumor size and tumors with more advanced stages. Transfection with uc.454 markedly induced apoptosis and inhibited cell proliferation in SPC-A-1 and NCI-H2170 LC cell lines. Above results suggested that uc.454 played a suppressive role in LC. Heat shock protein family A member 12B (HSPA12B) protein was negatively regulated by uc.454 at the posttranscriptional level by dual-luciferase reporter assay and affected the expressions of Bcl-2 family members, which finally induced LC apoptosis. The uc.454/HSPA12B axis furthers our understanding of the molecular mechanisms involved in tumor apoptosis, which may potentially serve as a therapeutic target for lung carcinoma.

Expression of uc.189 and its clinicopathologic significance in gynecological cancers.

In recent decades, emerging evidence demonstrates that ultraconserved elements (UCEs) encoding noncoding RNAs serve as regulators of gene expression. Until now, the role of uc.189 in human cancers remains undefined and the clinical significance of uc.189 in gynecological cancers remains unknown. This study was to identify the prognostic value of uc.189 expression in gynecological cancers. Tissue microarrays were constructed with 243 samples including 116 cervical squamous cell carcinomas (CSCCs), 98 endometrial adenocarcinomas (EACs), 29 ovarian cystoadenocarcinomas(OCAs), and corresponding normal tissues. In CSCC, uc.189 expression was increased in 78.5% of cases (91/116), decreased in 4.3% (5/116), and unchanged in 17.2% (20/116). In EAC its expression was increased in 74.5% (73/98), decreased in 3.1% (3/98), and unchanged in 22.4% (22/98). Expression of uc.189 was increased in 23, and unchanged/decreased in 6, of 29 cases of ovarian cystoadenocarcinomas. Univariate and multivariate Cox regression analysis demonstrated that over-expression of uc.189 predicted poor prognosis in CSCC and EAC. Thus, these findings suggested uc.189 might be an evaluating prognosis marker of gynecological tumors.

TUCR.454 inhabits metastasis in lung cancer cells.

Transcribed ultraconserved regions (TUCRs) belong to long non-coding RNAs (lncRNAs) are transcripts longer than 200 base pair RNA with no protein-coding capacity. Previous studies showed that TUCRs serve as oncogenes or tumor suppressor genes are involved in tumorigenesis and cancer progressive. However, little is known about the expression level and biological role of TUCR.454 in lung carcinoma. Our data showed TUCR.454 is significantly down-regulated in NSCLC tissue and lung cancer cell lines, and the down-regulated TUCR.454 is associated with lymph node metastasis. Transfection with TUCR.454 markedly inhibited cell migration and invasion in A549 and H460 lung cancer cell lines. K-Ras was demonstrated to be negatively regulated by TUCR.454 at the posttranscriptional level by dual-luciferase reporter assay. Down-expression of K-Ras via siRNA inhibited NSCLC cell migration and down-regulates P63 and MMP9 in protein level, resembling that of overexpression of TUCR.454. In conclusion, these findings suggested that TUCR.454 acts as a novel tumor suppressor by targeting the K-Ras gene thus inhabiting lung cancer cell migration and invasion.

Circ-PAX2 promotes proliferation and metastasis by absorbing miR-186 in lung cancer cells.

Circ-RNAs are a type of non-coding-protein RNAs which act as an effector role in many physiological processes. However, the novel function of circ-PAX2 in lung carcinomas is still unidentified. The current study is to detect the expression of circ-PAX2 in lung squamous cell carcinoma (LSCC) tissues and the physiological functions of circ-PAX2. Circ-PAX2 was distinguished in LSCC samples and matched non-tumor samples by human circRNA microarray analysis and was validated to be up-regulated in 86 specimens of LSCC tissues and lung cancer cell lines by qRT-PCR. Functional validation experiments showed that knockdown of circ-PAX2 promoted apoptosis of lung carcinoma cells, and then suppressed proliferation and migration of tumor cells. Small interfering RNA (siRNA) to circ-PAX2 inhibited growth in lung tumor cells. Bioinformatics prediction and rescue experiments showed that circ-PAX2 was a target of microRNA-186, confirmed by qRT-PCR and double luciferase reporter assay. On the whole, our findings reveal that circ-PAX2 was up-regulated and may be an oncogene in lung cancer; its function was reducing apoptosis, promoting cell proliferation and migration in lung carcinoma cells, which might be a novel therapeutic targetgene in lung cancer.

Upregulation of uc.189 in patients with esophageal squamous cell carcinoma and its clinicopathologic value.

Ultraconserved elements (UCEs) encoding noncoding RNAs serve as important regulators in cancer biology. Until now, the role of the UCE uc.189 in human cancers remains undefined and the clinical significance of uc.189 in esophageal cancers remains unknown. This study was to identify the prognostic value of uc.189 expression in esophageal squamous cell carcinomas (ESCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of uc.189 in matched cancerous tissues and adjacent noncancerous tissues from 152 patients with ESCC. The correlation of uc.189 with clinicopathological features and prognosis were also analyzed. The expression of uc.189 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (122/152, 80.3%, p<0.01), and the high level of uc.189 expression was significantly correlated with invasion of the tumor (p=0.009), advanced clinical stage (p=0.000), lymph node metastasis (p=0.000), and poor prognosis. High expression of uc.189 might reflect poor prognosis of ESCC and indicate a potential diagnostic target in ESCC patients. Uc.189 might be considered as a novel molecule involved in ESCC progression, which provides a potential prognostic biomarker and therapeutic target.

TUC338 promotes cell migration and invasion by targeting TIMP1 in cervical cancer.

Ultraconserved regions (UCRs) are non-protein-coding gene sequences that are strictly conserved across numerous distinct species. It has been demonstrated previously that UCRs encoding non-coding RNAs serve as regulators of gene expression. In recent decades, there has been increasing evidence for the involvement of UCRs in carcinogenesis. In previous studies, the non-coding RNA transcribed ultraconserved element 338 (TUC338) was identified to serve an oncogenic role in hepatocellular cancer; however, thus far, the role of TUC338 in cervical cancer (CC) remains undefined. The results of the present study revealed that TUC338 is significantly upregulated in CC tissues and cell lines, and that the upregulation of TUC338 is associated with lymph node metastasis. Transfection with small interfering RNA (siRNA) against TUC338 could markedly inhibit cell migration and invasion in HeLa and C33A CC cell lines. Using a dual-luciferase reporter assay, tissue inhibitor of metalloproteinase 1 (TIMP1) was demonstrated to be negatively regulated by TUC338 at the post-transcriptional level, via a specific target site within the 3' untranslated region. The expression of TIMP1 was also observed to be inversely associated with TUC338 expression in CC tissues. Overexpression of TIMP1 with MigRI-TIMP1-green fluorescent protein inhibited CC cell migration and invasion and downregulated matrix metalloproteinase 9, resembling the effects of TUC338 siRNA. Therefore, the results of the present study suggest that TUC338 acts as a novel oncogene by targeting the TIMP1 gene, and inhibiting CC cell migration and invasion.