Abnormal Graphitization Behavior in Near-Surface/Interface Region of Polymer-Derived Ceramics.

The in situ free carbon generated in polymer-derived ceramics (PDCs) plays a crucial role in their unique microstructure and resultant properties. This study advances a new phenomenon of graphitization of PDCs. Specifically, whether in micro-/nanoscale films or millimeter-scale bulks, the surface/interface radically changes the fate of carbon and the evolution of PDC nanodomains, promotes the graphitization of carbon, and evolves a free carbon enriched layer in the near-surface/interface region. Affected by the enrichment behavior of free carbon in the near-surface/interface region, PDCs exhibit highly abnormal properties such as the skin behavior and edge effect of the current. The current intensity in the near-surface/interface region of PDCs is orders of magnitude higher than that in its interior. Ultrahigh conductivity of up to 14.47 S cm-1 is obtained under the action of the interface and surface, which is 5-8 orders of magnitude higher than that of the bulk prepared under the same conditions. Such surface/interface interactions are of interest for the regulation of free carbon and its resultant properties, which are the core of PDC applications. Finally, the first PDC thin-film strain gauge that can survive a butane flame with a high temperature of up to ≈1300 °C is fabricated.

CircRNAs in anticancer drug resistance: recent advances and future potential.

CircRNAs are a novel class of RNA molecules with a unique closed continuous loop structure. CircRNAs are abundant in eukaryotic cells, have unique stability and tissue specificity, and can play a biological regulatory role at various levels, such as transcriptional and posttranscriptional levels. Numerous studies have indicated that circRNAs serve a crucial purpose in cancer biology. CircRNAs regulate tumor behavioral phenotypes such as proliferation and migration through various molecular mechanisms, such as miRNA sponging, transcriptional regulation, and protein interaction. Recently, several reports have demonstrated that they are also deeply involved in resistance to anticancer drugs, from traditional chemotherapeutic drugs to targeted and immunotherapeutic drugs. This review is the first to summarize the latest research on circRNAs in anticancer drug resistance based on drug classification and to discuss their potential clinical applications.

Over-expressed long noncoding RNA HOXA11-AS promotes cell cycle progression and metastasis in gastric cancer.

BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as critical regulators in a variety of human cancers, including gastric cancer (GC). However, the function and mechanisms responsible for these molecules in GC are not fully understood. In our previous study, we found that GC associated lncRNA HOXA11-AS is significantly upregulated in GC tissues. Over-expressed HOXA11-AS promotes GC cells proliferation and invasion through scaffolding the chromatin modification factors PRC2, LSD1 and DNMT1. METHODS: HOXA11-AS expression levels in GC cells was detected by quantitative real-time PCR (qPCR). HOXA11-AS siRNAs and overexpression vector were transfected into GC cells to down-regulate or up-regulate HOXA11-AS expression. In vitro and in vivo assays were performed to investigate the functional role of HOXA11-AS in GC cells cell cycle progression, invasion and metastasis. RIP and ChIP assays were used to determine the mechanism of HOXA11-AS's regulation of underlying targets. RESULTS: We found that knockdown of HOXA11-AS induced GC cells G0/G1 phase arrest and suppressed GC cells migration, invasion and metastasis in vivo. Moreover, mechanistic investigation showed that HOXA11-AS could interact with WDR5 and promote ß-catenin transcription, bind with EZH2 and repress P21 transcription, and induce KLF2 mRNA degradation via interacting with STAU1. CONCLUSIONS: Taken together, these findings show that HOXA11-AS not only could promote GC cells migration and invasion in vitro, but also promotes GC cells metastasis in vivo, at least in part, by regulating ß-catenin and KLF2.

Long intergenic non-coding RNA 00152 promotes lung adenocarcinoma proliferation via interacting with EZH2 and repressing IL24 expression.

BACKGROUND: Numerous studies have shown that long non-coding RNAs (lncRNAs) behave as a novel class of transcript during multiple cancer processes, such as cell proliferation, apoptosis, migration, and invasion. LINC00152 is located on chromosome 2p11.2, and has a transcript length of 828 nucleotides. The biological role of LINC00152 in LAD(lung adenocarcinoma) remains unknown. METHODS: Quantitative reverse transcription PCR(qRT-PCR) was used to detect LINC00152 expression in 60 human LAD tissues and paired normal tissues. In vitro and in vivo studies showed the biological function of LINC00152 in tumour progression. RNA transcriptome sequencing technology was performed to identify the downstream suppressor IL24(interleukin 24) which was further examined by qRT-PCR, western bolt and rescue experiments. RNA immunoprecipitation (RIP), RNA pulldown, and Chromatin immunoprecipitation (ChIP) assays were carried out to reveal the interaction between LINC00152, EZH2 and IL24. RESULTS: LINC00152 expression was upregulated in 60 human LAD tissues and paired normal tissues. High levels of LINC00152 expression were correlated with advanced TNM stage, larger tumor size, and lymph node metastasis, as well as shorter survival time. Silencing of LINC00152 suppressed cell growth and induced cell apoptosis. LINC00152 knockdown altered the expression of many downstream genes, including IL24. LINC00152 could interact with EZH2 and inhibit IL24 transcription. Moreover, the ectopic expression of IL24 repressed cell proliferation and partly reversed LINC00152 overexpression-induced promotion of cell growth in LAD. CONCLUSIONS: Our study reveals an oncogenic role for LINC00152 in LAD tumorigenesis, suggesting that it could be used as a therapeutic target in LAD treatment.

Direct write micro/nano optical fibers by near-field melt electrospinning.

A simple fabrication method of micro/nano-optical fibers (MNOFs) based on near-field melt electrospinning (NMES) is proposed in this Letter. Single fibers with diameters ranging from 500 nm to 6 µm were directly written by near-field electrospinning of molten poly(methyl methacrylate) (PMMA). The morphology and transmission characteristics of single PMMA MNOFs were experimentally measured. The results showed that PMMA MNOFs have the advantages of smooth surfaces, uniform diameters, and low loss. As an example of one-step fabrication for MNOF devices, a planar helical MNOF structure was directly written and optically characterized. To demonstrate the versatility of the NMES process, in combination with the microfluidic technique, a liquid refractive index-sensing chip was fabricated and tested. Our results demonstrate that the proposed fabrication method has strong potential in the direct writing of patterned optical devices and heterogeneous integrated devices.

KLF15 Inhibits Cell Proliferation in Gastric Cancer Cells via Up-Regulating CDKN1A/p21 and CDKN1C/p57 Expression.

BACKGROUND: Krüppel-like factors (KLFs) have been identified in multi-cancers and act as oncogenes or tumor suppressors. The function of KLF15, one member of KLFs, has not been well elucidated, especially in gastric cancer (GC). AIMS: This study was designed to investigate the prognostic value and biological functions of KLF15 in GC. METHODS: KLF15 protein expression in GC patients was evaluated by immunohistochemistry assays in 50 paired GC tissues and adjacent normal tissues, and correlations between KLF15 expression and clinicopathological characteristics and prognosis were analyzed. Then, we investigated the over-expression of KLF15 on cell proliferation and its mechanism in GC cells. RESULTS: KLF15 expression levels were significantly down-regulated in GC tissues compared to adjacent normal tissues. And KLF15 expression was negatively correlated with clinical stage, lymphatic metastasis, and distant metastasis. Furthermore, KLF15 expression could predict prognosis in patients with GC. Moreover, over-expression of KLF15 could inhibit cell proliferation partly via regulating CDKN1A/p21 and CDKN1C/p57. CONCLUSION: These findings demonstrate that KLF15 plays a significant role in GC progression and could be a therapeutic target for GC.

Exosomal circRHCG promotes breast cancer metastasis via facilitating M2 polarization through TFEB ubiquitination and degradation.

Triple-negative breast cancer (TNBC) is a highly aggressive cancer with distant metastasis. Accumulated evidence has demonstrated that exosomes are involved in TNBC metastasis. Elucidating the mechanism underlying TNBC metastasis has important clinical significance. In the present study, exosomes were isolated from clinical specimens and TNBC cell lines. Colony formation, EdU incorporation, wound healing, and transwell assays were performed to examine TNBC cell proliferation, migration, and metastasis. Macrophage polarization was evaluated by flow cytometry and RT-qPCR analysis of polarization markers. A mouse model of subcutaneous tumor was established for assessment of tumor growth and metastasis. RNA pull-down, RIP and Co-IP assays were used for analyzing molecular interactions. Here, we proved that high abundance of circRHCG was observed in exosomes derived from TNBC patients, and increased exosomal circRHCG indicated poor prognosis. Silencing of circRHCG suppressed TNBC cell proliferation, migration, and metastasis. TNBC cell-derived exosomes promoted M2 polarization via delivering circRHCG. Exosomal circRHCG stabilized BTRC mRNA via binding FUS and naturally enhanced BTRC expression, thus promoting the ubiquitination and degradation of TFEB in THP-1 cells. In addition, knockdown of BTRC or overexpression of TFEB counteracted exosomal circRHCG-mediated facilitation of M2 polarization. Furthermore, exosomal circRHCG promoted TNBC cell proliferation and metastasis by facilitating M2 polarization. Knockdown of circRHCG reduced tumor growth, metastasis, and M2 polarization through the BTRC/TFEB axis in vivo. In summary, exosomal circRHCG promotes M2 polarization by stabilizing BTRC and promoting TFEB degradation, thereby accelerating TNBC metastasis and growth. Our study provides promising therapeutic strategies against TNBC.

Conformal Fabrication of Thick Film Platinum Strain Gauge Via Error Regulation Strategies for In Situ High-Temperature Strain Detection.

Monitoring high-temperature strain on curved components in harsh environments is a challenge for a wide range of applications, including in aircraft engines, gas turbines, and hypersonic vehicles. Although there are significant improvements in the preparation of high-temperature piezoresistive film on planar surfaces using 3D printing methods, there are still difficulties with poor surface compatibility and high-temperature strain testing on curved surfaces. Herein, a conformal direct ink writing (CDIW) system coupled with an error feedback regulation strategy was used to fabricate high-precision, thick films on curved surfaces. This strategy enabled the maximum amount of error in the distance between the needle and the substrate on a curved surface to be regulated from 155 to 4 µm. A conformal Pt thick-film strain gauge (CPTFSG) with a room-temperature strain coefficient of 1.7 was created on a curved metallic substrate for the first time. The resistance drift rate at 800 °C for 1 h was 1.1%, which demonstrated the excellent stability and oxidation resistance of the CPTFSG. High-temperature dynamic strain tests up to 769 °C revealed that the sensor had excellent high-temperature strain test performance. Furthermore, the CPTFSG was conformally deposited on an aero-engine turbine blade to perform in situ tensile and compressive strain testing at room temperature. High-temperature strain tests were conducted at 100 and 200 °C for 600 and 580 µÎµ, respectively, demonstrating a high steady-state response consistent with the commercial high-temperature strain transducer. In addition, steady-state strain tests at high temperatures up to 496 °C were tested. The CDIW error modulation strategy provides a highly promising approach for the high-precision fabrication of Pt thick films on complex surfaces and driving in situ sensing of high-temperature parameters on curved components toward practical applications.

Rapid laser fabrication of indium tin oxide and polymer-derived ceramic composite thin films for high-temperature sensors.

Thin-film sensors are essential for real-time monitoring of components in high-temperature environments. Traditional fabrication methods often involve complicated fabrication steps or require prolonged high-temperature annealing, limiting their practical applicability. Here, we present an approach using direct ink writing and laser scanning (DIW-LS) to fabricate high-temperature functional thin films. An indium tin oxide (ITO)/preceramic polymer (PP) ink suitable for DIW was developed. Under LS, the ITO/PP thin film shrank in volume. Meanwhile, the rapid pyrolysis of PP into amorphous precursor-derived ceramic (PDC) facilitated the faster sintering of ITO nanoparticles and improved the densification of the thin film. This process realized the formation of a conductive network of interconnected ITO nanoparticles. The results show that the ITO/PDC thin film exhibits excellent stability, with a drift rate of 4.7 % at 1000 °C for 25 h, and withstands temperatures up to 1250 °C in the ambient atmosphere. It is also sensitive to strain, with a maximum gauge factor of -6.0. As a proof of concept, we have used DIW-LS technology to fabricate a thin-film heat flux sensor on the surface of the turbine blade, capable of measuring heat flux densities over 1 MW/m2. This DIW-LS process provides a viable approach for the integrated, rapid, and flexible fabrication of thin film sensors for harsh environments.

Rapid Printing of High-Temperature Polymer-Derived Ceramic Composite Thin-Film Thermistor with Laser Pyrolysis.

Polymer-derived ceramic (PDC)-based high-temperature thin-film sensors (HTTFSs) exhibit promising applications in the condition monitoring of critical components in aerospace. However, fabricating PDC-based HTTFS integrated with high-efficiency, high-temperature anti-oxidation, and customized patterns remains challenging. In this work, we introduce a rapid and flexible selecting laser pyrolysis combined with a direct ink writing process to print double-layer high-temperature antioxidant PDC composite thin-film thermistors under ambient conditions. The sensitive layer (SL) was directly written on an insulating substrate with excellent conductivity by laser-induced graphitization. Then, the antioxidant layer (AOL) was written on the surface of the SL to realize the integrated manufacturing of double-functional layers. Through characterization analysis, it was shown that B2O3 and SiO2 glass phases generated by the PDC composite AOL could effectively prevent oxygen intrusion. Therefore, the fabricated PDC composite thermistors exhibited a negative temperature coefficient in the temperature range from 100 to 1100 °C and high repeatability below 800 °C. Meanwhile, it has excellent high-temperature stability at 800 °C with a resistance change of only 2.4% in 2 h. Furthermore, the high-temperature electrical behavior of the thermistor was analyzed. The temperature dependence of the conductivity for this thermistor has shown an agreement with the Mott's variable range hopping mechanism. Additionally, the thermistor was fabricated on the surface of an aero-engine blade to verify its feasibility below 800 °C, showing the great potential of this work for state sensing on the surface of high-temperature components, especially for customized requirements.

High-Linearity Flexible Pressure Sensor Based on the Gaussian-Curve-Shaped Microstructure for Human Physiological Signal Monitoring.

Flexible pressure sensors with high-performance show broad application prospects in health monitoring, wearable electronic devices, intelligent robot sensing, and other fields. Although flexible pressure sensors have made significant progress in sensitivity and detection range, most of them still exhibit strong nonlinearity, which leads to significant troubles in signal acquisition and thus limits their popularity in practical applications. It remains a serious challenge for the flexible pressure sensor to achieve high linearity while maintaining high sensitivity. Herein, a doped sensing membrane with a uniformly distributed Gaussian-curve-shaped micropattern array was developed using the micro-electromechanical systems (MEMS) process, and a flexible sensor structure with the doped film as the core was designed and constructed. The prototype sensor has a high sensitivity of 1.77 kPa-1 and a linearity of 0.99 in the full detection range of 20 Pa to 30 kPa. In addition, its excellent performance also includes fast response/recovery times (∼25/50 ms) and long-term endurance (>10,000 cycles at 15 kPa). The prototype sensor has been successfully demonstrated in human pulse monitoring, speech recognition, and gesture recognition. The 2 × 6 sensor array can detect the spatial pressure distribution. Thus, such a microstructure shape design will open a new way to fabricate a high-linearity pressure sensor for potential applications in health monitoring, human-machine interaction, etc.

Thin-Film Platinum Resistance Temperature Detector with a SiCN/Yttria-Stabilized Zirconia Protective Layer by Direct Ink Writing for High-Temperature Applications.

In situ temperature monitoring of curved high-temperature components in extreme environments is challenging for a variety of applications in fields such as aero engines and gas turbines. Recently, extrusion-based direct ink writing (DIW) has been utilized to fabricate platinum (Pt) resistance temperature detectors (RTDs). However, the current Pt RTD prepared by DIW technology suffers from a limited temperature range and poor high-temperature stability. Here, DIW technology and yttria-stabilized zirconia (YSZ)-modified precursor ceramic film packaging have been used to build a Pt RTD with high-temperature resistance, small disturbance, and high stability. The results indicate that the protective layer formed by the liquid phase anchors the Pt particles and reduces the agglomeration and volatilization of the Pt sensitive layer at high temperature. Attributed to the SiCN/YSZ protective layer, the temperature resistance curve of the Pt RTD in the range of 50-800 °C has little deviation from the fitting curve, and the fitting correlation coefficient is above 0.9999. Interestingly, the Pt RTD also has high repeatability and stability. The high temperature resistance drift rate is only 0.05%/h after 100 h of long-term testing at 800 °C and can withstand butane flame up to ∼1300 °C without damage. Moreover, the Pt RTD can be conformally deposited on the outer ring of aerospace bearings by DIW technology and then realize on-site, nondestructive, and real-time monitoring of bearing temperature. The fabricated Pt RTD shows great potential for high-temperature applications, and the novel technology proposed provides a feasible pathway for temperature monitoring of aeroengine internal curved hot-end components.

All-Three-Dimensionally-Printed AgPd Thick-Film Strain Gauge with a Glass-Ceramic Protective Layer for High-Temperature Applications.

A high-temperature thin/thick-film strain gauge (TFSG) shows development prospects for in situ strain monitoring of hot-end components due to their small perturbations, no damage, and fast response. Direct ink writing (DIW) 3D printing is an emerging and facile approach for the rapid fabrication of TFSG. However, TFSGs prepared based on 3D printing with both high thermal stability and low temperature coefficient of resistance (TCR) over a wide temperature range remain a great challenge. Here, we report a AgPd TFSG with a glass-ceramic protective layer based on DIW. By encapsulating the AgPd sensitive layer and regulating the Pd content, the AgPd TFSG demonstrated a low TCR (191.6 ppm/°C) from 50 to 800 °C and ultrahigh stability (with a resistance drift rate of 0.14%/h at 800 °C). Meanwhile, the achieved specifications for strain detection included a strain sensing range of ±500 µÎµ, fast response time of 153 ms, gauge factor of 0.75 at 800 °C, and high durability of >8000 cyclic loading tests. The AgPd TFSG effectively monitors strain in superalloys and can be directly deposited onto cylindrical surfaces, demonstrating the scalability of the presented approach. This work provides a strategy to develop TFSGs for in situ sensing of complex curved surfaces in harsh environments.

A Whole New Comprehension about ncRNA-Encoded Peptides/Proteins in Cancers.

It is generally considered that non-coding RNAs do not encode proteins; however, more recently, studies have shown that lncRNAs and circRNAs have ORFs which are regions that code for peptides/protein. On account of the lack of 5'cap structure, translation of circRNAs is driven by IRESs, m6A modification or through rolling amplification. An increasing body of evidence have revealed different functions and mechanisms of ncRNA-encoded peptides/proteins in cancers, including regulation of signal transduction (Wnt/ß-catenin signaling, AKT-related signaling, MAPK signaling and other signaling), cellular metabolism (Glucose metabolism and Lipid metabolism), protein stability, transcriptional regulation, posttranscriptional regulation (regulation of RNA stability, mRNA splicing and translation initiation). In addition, we conclude the existing detection technologies and the potential of clinical applications in cancer therapy.

ZrB2/SiCN Thin-Film Strain Gauges for In-Situ Strain Detection of Hot Components.

The in-situ strain/stress detection of hot components in harsh environments remains a challenging task. In this study, ZrB2/SiCN thin-film strain gauges were fabricated on alumina substrates by direct writing. The effects of ZrB2 content on the electrical conductivity and strain sensitivity of ZrB2/SiCN composites were investigated, and based on these, thin film strain gauges with high electrical conductivity (1.71 S/cm) and a gauge factor of 4.8 were prepared. ZrB2/SiCN thin-film strain gauges exhibit excellent static, cyclic strain responses and resistance stability at room temperature. In order to verify the high temperature performance of the ZrB2/SiCN thin-film strain gauges, the temperature-resistance characteristic curves test, high temperature resistance stability test and cyclic strain test were conducted from 25 °C to 600 °C. ZrB2/SiCN thin-film strain gauges exhibit good resistance repeatability and stability, and highly sensitive strain response, from 25 °C to 600 °C. Therefore, ZrB2/SiCN thin-film strain gauges provide an effective approach for the measurement of in-situ strain of hot components in harsh environments.

Additive-Manufactured Platinum Thin-Film Strain Gauges for Structural Microstrain Testing at Elevated Temperatures.

This paper investigates the feasibility and performance of the fabrication of platinum high-temperature thin-film strain sensors on nickel-based alloy substrates by additive manufacturing. The insulating layer was made of a dielectric paste by screen printing process. A 1.8-micron-thick platinum film was deposited directly on the insulating layer. The four-wire resistance measurement method was used to eliminate the contact resistance of the solder joints. Comprehensive morphological and electrical characterization of the platinum thin-film strain gauge was carried out, and good static and dynamic strain responses were obtained, which confirmed that the strain gauge was suitable for in situ strain monitoring of high-temperature complex components.

In Situ Laser Fabrication of Polymer-Derived Ceramic Composite Thin-Film Sensors for Harsh Environments.

Polymer-derived ceramic (PDC) is considered an excellent sensing material for harsh environments such as aero-engines and nuclear reactors. However, there are many inherent limitations not only in pure PDC but also in its common fabrication method by furnace thermolysis. Therefore, this study proposes a novel method of rapid in situ fabrication of PDC composite thin-film sensors by laser pyrolysis. Using this method with different fillers, a sensitive PDC composite film layer with high-quality graphite can be obtained quickly, which is more flexible and efficient compared to the traditional furnace thermolysis. Furthermore, this study analyzes the reaction differences between laser pyrolysis and furnace thermolysis. The laser pyrolysis method principally produces ß-SiC and enhances the graphitization of amorphous carbon, while the degree of graphitization by furnace thermolysis is low. In addition, it is capable of rapidly preparing an insulating PDC composite film, which still has a resistance of 5 MΩ at 600 °C. As a proof of this method, the PDC composite thin-film strain sensors are fabricated in situ on nickel alloys and aluminum oxide substrates, respectively. The sensor fabricated on the nickel alloy with a high gauge factor of over 100 can be used in high-temperature environments below 350 °C without the protection of an oxidation-resistant coating. In this way, the approach pioneers the in situ laser fabrication of functional PDC films for sensors, and it has great potential for the in situ sensing of complex curved surfaces in harsh environments.

LncRNA LINC01116 Contributes to Cisplatin Resistance in Lung Adenocarcinoma.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been found to contribute to cisplatin resistance in several cancers; however, the role of lncRNA LINC01116 in cisplatin resistance remains unknown in non-small-cell lung cancer. This study aimed to examine the contribution of LINC01116 to cisplatin resistance in lung adenocarcinoma (LAD). MATERIALS AND METHODS: Cisplatin-resistant A549/DDP cells were generated by treatment with cisplatin by dose escalation. LINC01116 expression was compared between A549 and A549/DDP cells, and between cisplatin-resistant and non-resistant LAD specimens. The cell viability, colony formation, proliferation, migration and invasion were measured using MTT and Transwell assays, and cell apoptosis and cell cycle were detected using flow cytometry. The expression of E-cadherin and Vimentin was quantified. LAD xenografts were modeled in nude mice to investigate the role of LINC01116 on the resistance of LAD to cisplatin. RESULTS: MTT assay measured the IC50 values of 13.49 ± 1.62 and 3.52 ± 1.33 µg/mL for A549/DDP and A549 cells, respectively. LINC01116 was overexpressed in cisplatin-resistant LAD specimens and A549/DDP cells (P < 0.05). Knockdown of LINC01116 inhibited cell viability, proliferation, migration and invasion, promoted apoptosis and enhanced the sensitivity to cisplatin in A549/DDP cells, while LINC01116 overexpression promoted cell viability, proliferation, migration and invasion, inhibited apoptosis and reduced the sensitivity to cisplatin in A549 cells. LINC01116 knockdown resulted in a 2.1-fold increase in E-cadherin expression and a 56% reduction in Vimentin expression in A549/DDP cells, and LINC01116 overexpression resulted in a 45% reduction in E-cadherin expression and a 1.82-fold increase in Vimentin expression in A549 cells. CONCLUSION: Dysregulation of lncRNA LINC01116 expression results in resistance of LAD to cisplatin via the EMT process. Our findings support the oncogenic role of LINC01116 to promote the development of cisplatin resistance in LAD, and LINC01116 may be a novel predictor of poor response to cisplatin.

The prognostic value of COL3A1/FBN1/COL5A2/SPARC-mir-29a-3p-H19 associated ceRNA network in Gastric Cancer through bioinformatic exploration.

Increasing studies on malignant tumors have proposed a new competing endogenous RNA (ceRNA) regulatory mechanism that mRNA, miRNA and lncRNA interact with each other. However, the mRNA-miRNA-lncRNA associated ceRNA network in gastric cancer remains unknown. We used online bioinformatic softwares to predict the hub genes and their upstream miRNAs and lncRNAs in gastric cancer, and then performed survival analyses. After collecting gastric cancer tissue samples and performing PCR experiments, the correlations among predicted mRNA, miRNA and lncRNA were further verified. A total of 101 up-regulated significant differentially expressed genes (DEGs) and 219 down-regulated significant DEGs in gastric cancer were confirmed. Functional enrichment analyses of these significant DEGs indicated that they were potentially enriched in some pathways involved in tumor malignant biological processes or metabolism. Then, we identified 20 hub genes in the PPI networks. Combined with expression and survival analyses, 8 up-regulated genes and 1 down-regulated gene were identified as central genes and acted as important prognostic roles in gastric cancer. 17 miRNAs were confirmed that might potentially regulate the expressions of these central genes. But only 8 out of them indicated better outcome in gastric cancer. Further, 79 lncRNAs were predicted that might have the potence to combine with the 8 central miRNAs. The lncRNA H19 was eventually defined as a central lncRNA by survival analyses. Stimultaneously, we found that there were certain interactions among lncRNA, miRNA and mRNAs in 50 gastric cancer tissues by qRT-PCR. Moreover, the high expression of H19 is associated with advanced TNM stage, primary tumor and lymph nodes, indicating a poor prognosis. In summary, we uncovered the prognostic value of COL3A1/FBN1/COL5A2/SPARC-mir-29a-3p-H19 ceRNA network in gastric cancer.

Long non-coding RNA CASC9 promotes gefitinib resistance in NSCLC by epigenetic repression of DUSP1.

Resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, has greatly affected clinical outcomes in non-small cell lung cancer (NSCLC) patients. The long noncoding RNAs (lncRNAs) are known to regulate tumorigenesis and cancer progression, but their contributions to NSCLC gefitinib resistance remain poorly understood. In this study, by analyzing the differentially expressed lncRNAs in gefitinib-resistant cells and gefitinib-sensitive cells in the National Institute of Health GEO dataset, we found that lncRNA CASC9 expression was upregulated, and this was also verified in resistant tissues. Gain and loss of function studies showed that CASC9 inhibition restored gefitinib sensitivity both in vitro and in vivo, whereas CASC9 overexpression promoted gefitinib resistance. Mechanistically, CASC9 repressed the tumor suppressor DUSP1 by recruiting histone methyltransferase EZH2, thereby increasing the resistance to gefitinib. Furthermore, ectopic expression of DUSP1 increased gefitinib sensitivity by inactivating the ERK pathway. Our results highlight the essential role of CASC9 in gefitinib resistance, suggesting that the CASC9/EZH2/DUSP1 axis might be a novel target for overcoming EGFR-TKI resistance in NSCLC.