Long noncoding RNA GPRC5D-AS1 in renal cell carcinoma: a molecular mechanism study.

Background: Clear cell renal cell carcinoma (RCC) is the most common subtype of RCC. Although targeted therapy can provide superior treatment outcomes, it is prone to drug resistance, and individual responses to immunotherapy vary greatly. Therefore, finding new diagnostic and therapeutic targets for RCC is of considerable importance. Long noncoding RNA (lncRNA) GPRC5D-AS1 can serve as a biomarker in clinical applications and the prognosis of lung squamous cell carcinoma. However, the specific mechanism of action of lncRNA GPRC5D-AS1 in RCC has not yet been clarified. Therefore, this paper explores the expression of lncRNA GPRC5D-AS1 in the renal cancer cell line 786-0, and conducts a preliminary study of its molecular mechanism. Selecting nude mice for tumor experiments is because of the high genomic and physiological similarity between mice and humans. Conducting tumor research on mice allows for better control of experimental conditions, aiding researchers in more accurately observing and analysing tumor characteristics and responses. Methods: Small interfering RNA (siRNA) and plasmid cloning DNA (pcDNA) 3.1 were used to transfect renal cancer cell line 786-0 to silence and overexpress the lncRNA GPRC5D-AS1 gene. Quantitative real-time fluorescence polymerase chain reaction was used to detect the difference in lncRNA GPRC5D-AS1 expression in blank control group, negative control group, siGPRC5D-AS1 group and oeGPRC5D-AS1 group. The effects of silence and overexpression of lncRNA GPRC5D-AS11 on the proliferation of 786-0 cells were detected in cell colony formation experiments; the changes in the migration and invasion of 786-0 cells were detected via cell scratch assay and transwell assay, respectively; the differences in tumor growth between groups were determined via tumorigenesis experiments in nude mice; and the expression of proliferation-related protein [ß-catenin, Ki67 and proliferating cell nuclear antigen (PCNA)] and invasion-related protein (N-cadherin and E-cadherin) were detected via Western blotting. Results: Compared with blank control group and negative control group, the siGPRC5D-AS1 group showed a significant decrease in the relative expression of lncRNA GPRC5D-AS1 (P<0.05), a significant increase in the number of proliferating cells and migrating cells (P<0.05), a significant increase in the tumor volume of nude mice (P<0.05), a significant increase in ß-catenin, Ki67, PCNA and N-cadherin protein expression (P<0.05), and a significant decrease in E-cadherin protein expression (P<0.05); conversely, these results were opposite for the eGPRC5D-AS1 group. Conclusions: Silencing the expression of lncRNA GPRC5D-AS1 can enhance the proliferation, invasion, and migration ability of renal cancer cell line 786-0, which can be weakened by the overexpression of lncRNA GPRC5D-AS1.

Identification and verification of anoikis-related gene markers to predict the prognosis of patients with bladder cancer and assist in the diagnosis and treatment of bladder cancer.

Background: The recurrence and mortality rates of bladder cancer are extremely high, and its diagnosis and treatment are global concerns. The mechanism of anoikis is closely related to tumor metastasis. Methods: First, we obtained all the data needed for this study from a public database through a formal operational process. The data were then analyzed by bioinformatics technology. Through the limma package, we screened and obtained 313 anoikis-related genes [false discovery rate (FDR) <0.05, |log fold change (FC) | >0.585]. Then, through univariate independent prognostic analysis, we further screened 146 genes (P<0.05) related to the prognosis of bladder cancer from 313 differential genes. These 146 prognostically relevant differential genes were used for least absolute shrinkage and selection operator (LASSO) regression for further screening to obtain model-related genes and output model formulas. Through the nomogram, we can calculate the survival rate of patients more accurately. The accuracy of the nomogram was also confirmed by calibration curves, independent prognostic analysis, receiver operating characteristic (ROC) curves, decision curve analysis (DCA) curves. We then analysed the sensitivity of immunotherapy in bladder cancer patients with different risk scores via Tumor Immune Dysfunction and Exclusion (TIDE). Results: Through bioinformatics technology and public databases, a prognostic model including 9 anoikis-related genes (KLF12, INHBB, CASP6, TGFBR3, FASN, TPM1, OGT, RAC3, ID4) was obtained. Integrating risk scores with clinical information, we obtained a nomogram that can accurately predict patient survival. By querying the immunohistochemical results of the Human Protein Atlas database, two of the nine model-related genes (FASN, RAC3) have the value of further research and are expected to become new biomarkers to assist the diagnosis and treatment of bladder cancer. Through immune-related analysis, we found that patients in the low-risk group appeared to be more suitable for immunotherapy, while drug sensitivity analysis showed that bladder cancer patients in the high-risk group were more sensitive to common chemotherapy drugs. Conclusions: In this study, a prognostic model that can accurately predict the prognosis of patients with bladder cancer was constructed. FASN and RAC3 are expected to become a new biomarker for the diagnosis and treatment of bladder cancer.

Multiple databases analyzed the prognosis prediction of renin secretion pathway-related genes in renal clear cell carcinoma and immunotherapy.

Background: Clear cell renal cell carcinoma (ccRCC) is a malignant kidney tumour and its progression is associated with the renin secretion pathway, so this study aimed to develop a prognostic model based on renin secretion pathway-related genes. Methods: First, 453 renin secretion pathway-related genes were acquired [|log fold change (FC)| >1.5, false discovery rate (FDR) <0.05] from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The data were combined and further screened for 188 genes associated with ccRCC prognosis (P<0.05) by univariate independent prognostic analysis. These genes were subjected to least absolute shrinkage and selection operator regression to identify potential prognostic genes to construct the prognostic model. The stability of the model was externally validated. Combined risk scores and clinical information were used to create nomograms to accurately reflect patient survival. The model-related genes were further mined for subsequent analysis. Results: A prognostic model of six renin secretion pathway genes (IGFBP3, PLAUR, CHKB-CPT1B, HOXA13, CDH13, and CDC20) was developed. Its reliability in predicting disease prognosis was confirmed by survival analysis, receiver operating characteristic (ROC) curve analysis and a risk curve. The nomogram and calibration curve showed good accuracy. The immune-related analyses revealed that the low-risk group would benefit more from immunotherapy. Conclusions: The prognostic model of ccRCC based on six renin secretion pathway-related genes can be used to guide the precise treatment of ccRCC patients.

Development and Evaluation of an Ensemble-Based Data Assimilation System for Regional Reanalysis Over the Tibetan Plateau and Surrounding Regions.

The Tibetan Plateau is regarded as the Earth's Third Pole, which is the source region of several major rivers that impact more 20% the world population. This high-altitude region is reported to have been undergoing much greater rate of weather changes under global warming, but the existing reanalysis products are inadequate for depicting the state of the atmosphere, particularly with regard to the amount of precipitation and its diurnal cycle. An ensemble Kalman filter (EnKF) data assimilation system based on the limited-area Weather Research and Forecasting (WRF) model was evaluated for use in developing a regional reanalysis over the Tibetan Plateau and the surrounding regions. A 3-month prototype reanalysis over the summer months (June-August) of 2015 using WRF-EnKF at a 30-km grid spacing to assimilate nonradiance observations from the Global Telecommunications System was developed and evaluated against independent sounding and satellite observations in comparison to the ERA-Interim and fifth European Centre for Medium-Range Weather Forecasts Reanalysis (ERA5) global reanalysis. Results showed that both the posterior analysis and the subsequent 6- to 12-hr WRF forecasts of the prototype regional reanalysis compared favorably with independent sounding observations, satellite-based precipitation versus those from ERA-Interim and ERA5 during the same period. In particular, the prototype regional reanalysis had clear advantages over the global reanalyses of ERA-Interim and ERA5 in the analysis accuracy of atmospheric humidity, as well as in the subsequent downscale-simulated precipitation intensity, spatial distribution, diurnal evolution, and extreme occurrence.

MECP2 gene mutation analysis in Chinese patients with Rett syndrome.

Rett syndrome (RTT) is a progressive neurodevelopmental disorder that affects almost exclusively girls. Mutations in the X-linked methyl-CpG-binding protein 2 gene (MECP2) have been found to be a cause. In order to study the spectrum of MECP2 mutations in Chinese patients, we employed PCR and sequencing of the coding region of MECP2 gene in 31 Chinese cases of classical sporadic RTT. Mutations in MECP2 were found in about 55%. Twelve different mutations in exon 3 were identified in 17 of these 31 patients; two of these are novel. A novel missense variant was detected in the C-terminal region in a patient and her father who was normal. In addition, there was a single nucleotide variant in the 3'UTR.