UBTF facilitates melanoma progression via modulating MEK1/2-ERK1/2 signalling pathways by promoting GIT1 transcription.

BACKGROUND: UBTF is an HMGB-box DNA binding protein and a necessary Pol I/Pol II basal transcription factor. It has been found that UBTF involves in carcinogenesis and progression of a few cancers. Nevertheless, the the biological function and potential molecular mechanism of UBTF in melanoma are still not clear and need to be clarified. METHODS: UBTF and GIT1 expressions in melanoma specimens and cell lines were examined by quantitative real-time PCR (qRT-PCR) and Western blot. MTT and colony formation assays were used to investigate the effects of UBTF and GIT1 on melanoma cell proliferation. Cell cycle and apoptosis assays were detected by flow cytometry. Tumor formation assay was used to analyze the effect of UBTF on melanoma growth. Bioinformatics predicting, chromatin immunoprecipitation (ChIP)-qRT-PCR and reporter gene assay were fulfilled for verifing GIT1 as UBTF targeting gene. RESULTS: Here we reported that UBTF mRNA and protein expressions were upregulated in primary melanoma specimens and cell lines. UBTF overexpression facilitated melanoma cell proliferation and cell cycle progression and restrained. Silencing UBTF suppressed cell multiplication, cell cycle progression and tumor growth, and promoted apoptosis. UBTF expression was positively related with GIT1 expression in human melanoma tissues. It was verified that UBTF promoted GIT1 transcription in melanoma cells through binding to the promoter region of GIT1. Furthermore, GIT1 overexpression promoted melanoma cell growth and suppressed apoptosis. Knockdown of GIT1 inhibited cell multiplication and induced apoptosis. Overexpression of GIT1 eliminated the effects of silencing UBTF on melanoma cells. Importantly, UBTF activated MEK1/2-ERK1/2 signalling pathways by upregulating GIT1 expression. CONCLUSIONS: Our study demonstrates that UBTF promotes melanoma cell proliferation and cell cycle progression by promoting GIT1 transcription, thereby activating MEK1/2-ERK1/2 signalling pathways. The findings indicate that UBTF plays a crucial function in melanoma and may be a potential therapeutic target for the treatment of this disease.

ZFPM2-AS1 facilitates cell proliferation and migration in cutaneous malignant melanoma through modulating miR-650/NOTCH1 signaling.

Aberrant expression of long non-coding RNA (lncRNA) zinc finger protein, FOG family member 2 antisense RNA 1 (ZFPM2-AS1) has been identified in many tumors, but its role in cutaneous malignant melanoma remains largely obscure. Our present study was intended to unveil the role and potential mechanism of ZFPM2-AS1 in cutaneous malignant melanoma. RT-qPCR was utilized to analyze ZFPM2-AS1 expression in cutaneous malignant melanoma cells. Cell counting kit-8 (CCK-8), colony formation, flow cytometry, and transwell analyses were utilized to assess ZFPM2-AS1 function on cell proliferation, apoptosis, and migration. Luciferase reporter, RNA immunoprecipitation, and RNA-pull down assays were applied to probe the regulatory mechanism of ZFPM2-AS1 in cutaneous malignant melanoma cells. Up-regulation of ZFPM2-AS1 was discovered in cutaneous malignant melanoma cells. ZFPM2-AS1 deletion restrained cell proliferation, migration, and elevated cell apoptosis in cutaneous malignant melanoma. ZFPM2-AS1 regulated notch receptor 1 (NOTCH1) to activate the NOTCH pathway. ZFPM2-AS1 acted as a competing endogenous RNA (ceRNA) to affect NOTCH1 expression via sponging miR-650. Collectively, ZFPM2-AS1 exerted an oncogenic role in cutaneous malignant melanoma progression via targeting miR-650/NOTCH1 signaling. Our study might offer a novel sight for cutaneous malignant melanoma treatment.

MiR-637 suppresses melanoma progression through directly targeting P-REX2a and inhibiting PTEN/AKT signaling pathway.

MicroRNAs (miRNAs) play important roles in melanoma. Although miR-637 has been suggested to be a tumor suppressor in several cancers, its function in melanoma and the molecular mechanism behind that function remain unclear. In this study, we investigated the role of miR-637 in human melanoma and explored its relevant mechanisms. We found that the expression of miR-637 is significantly downregulated in melanoma tissues and cell lines. While overexpression of miR-637 inhibited melanoma cell proliferation and cell cycle G1-S transition, and induced apoptosis. Inhibition of miR-637 promoted cell proliferation and G1-S transition, and suppressed apoptosis. Subsequent investigation revealed that miR-637 expression was inversely correlated with P-REX2a expression in melanoma tissues. P-REX2a was determined to be a direct target of miR-637 by using a luciferase reporter assay. Overexpression of miR-637 decreased P-REX2a expression at both the mRNA and protein levels, and suppression of miR-637 increased P-REX2a expression. Importantly, silencing P-REX2a recapitulated the cellular and molecular effects seen upon miR-637 overexpression, whereas, overexpression of P-REX2a eliminated the effects of miR-637 overexpression on melanoma cells. Furthermore, both enforced expression of miR-637 or silencing of P-REX2a resulted in activation of PTEN, leading to a decline in AKT phosphorylation. Taken together, our study demonstrates that miR-637 inhibites melanoma cell proliferation by activation of AKT signaling pathway and induces apoptosis through regulation of Bcl-2/Bax expression via targeting P-REX2a. These findings suggest that miR-637 plays a crucial role in melanoma progression, and may serve as a potential novel target for melanoma therapy.

Value analysis of ITLN1 in the diagnostic and prognostic assessment of colorectal cancer.

Background: Colorectal cancer (CRC) remains the leading cause of cancer death worldwide. Less than half of the patients are diagnosed when the cancer is locally advanced. Several studies have shown that intelectin-1 (ITLN1) can serve as a key prognostic and therapeutic target for CRC. The purpose of this study was to investigate the clinical value of ITLN1 in CRC and to analyse its potential as a predictive biomarker for CRC. Methods: Colon adenocarcinoma (COAD) is the main type of CRC. COAD project in The Cancer Genome Atlas (TCGA) database served as the training cohort, and GSE39582 series in the Gene Expression Omnibus (GEO) database served as the external independent validation cohort. First, the difference in the expression level of ITLN1 between COAD tissue and normal tissue was analysed, and the results were verified via immunohistochemistry. The relationship between ITLN1 expression and the prognosis of COAD patients was evaluated via the heatmap and the Kaplan-Meier (KM) curve. The ITLN1 coexpressed gene set obtained by Pearson correlation analysis was used. The prognostic signatures that were significantly correlated with survival status were screened by Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. Finally, a nomogram related to ITLN1 was constructed based on the risk score of the prognostic signature and routine clinicopathological variables. Results: ITLN1 is significantly underexpressed in tumour tissues and can be used as a valuable tool to distinguish COAD. The high-expression group of ITLN1 was verified to have a greater survival rate. ITLN1 is significantly associated with a good prognosis in COAD patients. Six candidate genes (ITLN1 and MORC2, SH2D7, LGALS4, ATOH1, and NAT2) were selected for use in the Cox-LASSO regression analysis to calculate the risk score. Finally, a nomogram was constructed with a comprehensive risk score and clinicopathologic factors to successfully predict and verify the 1-year, 3-year, and 5-year survival probability. Conclusions: Our study established ITLN1 as an effective tool for CRC screening, diagnosis, and prognostic assessment, provided a basis for further study of the molecular function of ITLN1, and provided new insights for the mechanistic exploration and treatment of CRC.

Toward understanding the interaction of shale gas-water-carbon nexus in Sichuan-Chongqing region based on county-level water security evaluation.

This study develops a comprehensive framework for understanding the interaction of shale gas-water-carbon nexus in Sichuan-Chongqing region. Within this framework, a county-level water security index (WSI) evaluation system is structured. Spatial autocorrelation model and spatial matching degree model are integrated to illustrate the spatial agglomeration characteristics of water security and the water-carbon relationship, respectively. The impacts of shale gas development on water security and carbon emissions are evaluated based on identification of shale well productivity. Results show that about 25.17% of counties with WSI < 0.4 (unsafe), especially in the eastern region. The central cities (such as Chengdu and Neijiang) should take active steps to reach a safety threshold (WSI ≥ 0.6). Population growth can accelerate water security deterioration through uncertainty analysis. Moreover, the spatial matching degree between WSI and carbon emissions in most cities is extremely poor (< 0.5), implying that these cities should optimize their energy structure and promote green transformation. Water used for shale gas extraction can hardly be ignored from a county-scale perspective, especially in Tongliang, Tongnan, and Jianyang. The future shale gas development would pose a threat to the regional climate.

Risk factors and prognostic factors for inflammatory breast cancer with bone metastasis: A population-based study.

PURPOSE: Inflammatory breast cancer (IBC) is a rare type of breast cancer with poor prognosis. IBC patients with bone metastasis (BM) often suffer from many complications. This study was performed to identify risk factors with strong capability of predicting high BM risk for IBC patients and find prognostic factors for those patients. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was used to collect the clinicopathological and survival information of IBC patients. 966 IBC patients diagnosed between 2010 and 2015 were included to study the risk factors for developing BM by using Multivariable logistic regression. A total of 194 and 176 patients were included to analyze independent prognostic factors for overall survival (OS) and cancer specific survival (CSS) of IBC patients with BM respectively. RESULTS: Of the 966 IBC patients, 194 (20.1%) patients were with BM. The risk factors for developing BM in IBC patients included unmarried marital status, double breast tumor, N1 stage, N3 stage, and liver metastases had higher risk of BM, while those of uninsured status and triple negative breast cancer (TNBC) were less likely to have BM. Analysis of prognostic factors for OS and CSS of IBC patients with BM showed that TNBC subtype and liver metastases were independently significantly associated with poorer OS and CSS of BM patients, while chemotherapy could serve as an independent prognostic factor for better OS and CSS of BM patients. CONCLUSION: Marital status, double breast tumor, N1 stage, N3 stage, and liver metastases should be considered for prediction of BM in IBC patients. TNBC subtype and liver metastases may indicate poor survival and chemotherapy can indicate improved survival for IBC patients with BM.

Three-Dimensional Binary-Conductive-Network Silver Nanowires@Thiolated Graphene Foam-Based Room-Temperature Self-Healable Strain Sensor for Human Motion Detection.

A lot of attention has recently been focused on wearable strain sensors because of their promising applications in the rising areas of human motion detection, health monitoring, and smart human-machine interaction. However, the design and fabrication of self-healable strain sensors with superior overall properties including stretchability, sensitivity, response ability, stability, and durability is still a huge challenge. Herein, we report an innovative self-healable strain sensor with exceptional overall performance constructed with three-dimensional binary-conductive-network silver nanowire-coated thiolated graphene foam (AgNWs@TGF) and room-temperature self-healing functionalized polyurethane (FPU) elastomer. Taking advantage of the good ductility and continuity of the AgNWs@TGF binary structure and the excellent resilience of the FPU, the strain sensor exhibits good stretchability (up to 60% strain), high sensitivity [gauge factor (GF) of 11.8 at 60% strain and detection limit of 0.1% strain], fast response ability (response/recovery time of 40/84 ms), and exceptional durability for 800 cycles of fatigue test. Besides, the highly flexible polydimethylsiloxane chains, strong intermolecular hydrogen bonding, and dynamic exchange reaction of aromatic disulfides ensure the sensor excellent recovery property of electrical conductivity, and the GF of sensor after self-healed only increases slightly. More importantly, the sensor is successfully applied for detecting a variety of human motions including pulse beats, voice recognitions, various joint movements, and handwriting. The method for preparing room-temperature self-healable strain sensor is facile, scalable, and cost-effective. The finds provide a new perspective on fabricating new-generation high-performance and functional strain sensors for health monitoring, wearable electronics, and intelligent robots.

Thiolated Graphene@Polyester Fabric-Based Multilayer Piezoresistive Pressure Sensors for Detecting Human Motion.

In the past several years, wearable pressure sensors have engendered a new surge of interest worldwide because of their important applications in the areas of health monitoring, electronic skin, and smart robots. However, it has been a great challenge to simultaneously achieve a wide pressure-sensing range and high sensitivity for the sensors until now. Herein, we proposed an innovative strategy to construct multilayer-structure piezoresistive pressure sensors with an in situ generated thiolated graphene@polyester (GSH@PET) fabric via the one-pot method. Taking advantage of the spacing among the rough fabric layers and the highly conductive GSH, the sensor realized not only a wide pressure range (0-200 kPa), but also high sensitivity (8.36 and 0.028 kPa-1 in the ranges of 0-8 and 30-200 kPa, respectively). After 500 loading-unloading cycles, the sensor still kept high sensitivity and a stable response, exhibiting great potential in long-term practical applications. Importantly, the piezoresistive pressure sensor was successfully applied to accurately detect different human behaviors including pulse, body motion, and voice recognition. Additionally, the sensing network integrated by the sensors also realized mapping and identifying spatial pressure distribution. Our method to construct the wide-range and high-sensitivity piezoresistive pressure sensor is facile, cost-effective, and available for mass production. The findings provide a new direction to fabricate the new-generation high-performance sensors for healthcare, interactive wearable devices, electronic skin, and smart robots.

Astragalin Attenuates UVB Radiation-induced Actinic Keratosis Formation.

BACKGROUND: Actinic Keratosis (AK), is the most common precancerous skin lesion induced by the excessive Ultraviolet B (UVB) and is a significant threat to the public health. UVB exposure causes oxidative DNA damage and is considered to be a significant contributor to AK and subsequent development of skin cancer. Besides, activation of p38 MAPK also plays a significant role in the development of AK. OBJECTIVE: This study aimed at the development of a nature compound which can inhibit UVB-induced AK. METHOD: MTS Cell Proliferation Assay Kit was used to detect the toxicity of astragalin. HE-staining, Immunohistochemical, Western blot and Enzyme Linked Immunosorbent Assay were applied to examine the clinicopathologic feature of AK and the change of p38 MAPK signal pathway treated with astraglin under the condition of UVB in vitro and in vivo. Results：In our clinical findings revealed that p38 MAPK, phospho-MSK1, and γ -H2AX were significantly highly expressed in human AK tissue than the normal healthy skin tissue. Moreover, in vitro studies showed that UVB induced the phospho-MSK1 and γ-H2AX in a time- and dose-dependent manner in HaCaT cells. Further, in vitro kinase assay demonstrated that astragalin could directly bind to p38 MAPK and suppress p38 MAPK activity. Furthermore, astragalin exhibited no toxicity and suppressed the UVB-induced expression of phospho- MSK1 and γ -H2AX by suppressing p38 MAPK activity in a time-dependent and dose-dependent manner in HaCaT cells. The in vivo studies with animal UV model demonstrated that astragalin inhibited UVB-induced expression of phospho-MSK1 and γ-H2AX in Babl/c mice. CONCLUSION: These results suggested that p38 MAPK is a direct valid molecular target of astragalin for the attenuation of UVB-induced AK. Furthermore, astragalin could be a potential promising novel natural therapeutic agent for the prevention and management of UVB-induced AK with high target specificity and low toxicity.

CD147 silencing inhibits tumor growth by suppressing glucose transport in melanoma.

Melanoma is a very malignant disease and there are still no effective treatments. CD147 participates in the carcinogenesis of multiple human cancers and GLUT-1, as a glucose transporter, is associated with tumor growth. However, the function of CD147 and GLUT-1 in melanoma have not been completely understood. Thus, in this study we investigated the expression of CD147 and GLUT-1 in melanoma tissue, which were overexpressed compared with that in nevus tissue. In addition, CD147 and GLUT-1 were co-localized in the cytoplasm of human melanoma A375 cells. Immunoprecipitation proved that CD147 interacted with GLUT-1 at D105-199. Silencing CD147 by specific siRNA could downregulate GLUT-1 level via inhibiting PI3K/Akt signaling and decrease glucose uptake in A375 cells. In vivo experiments also supported that CD147 knockdown suppressed the tumor growth in melanoma subcutaneous mice model, observed by micro PET/CT. Our results could help validate CD147 as a new therapeutic target for treating melanoma.