Research Progress on Porcine Reproductive and Respiratory Syndrome Virus NSP7 Protein.

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious and severe infectious disease caused by the PRRS virus (PRRSV). PRRS is characterized by reproductive disorders in sows and respiratory dysfunction in pigs. Non-structural protein 7 (NSP7) is one of the most conserved functional proteins in PRRSV, and it plays an important role in viral replication and humoral immune responses in infected hosts. This review discusses the biological characteristics of NSP7 to provide theoretical support for its application in PRRS diagnosis, novel vaccine design, and therapeutic drug development.

Variations in the NSP4 gene of the type 2 porcine reproductive and respiratory syndrome virus isolated in China from 1996 to 2021.

Porcine reproductive and respiratory syndrome virus (PRRSV) has continuously mutated since its first isolation in China in 1996, leading to difficulties in infection prevention and control. Infections caused by PRRSV-2 strains are the main epidemic strains in China, as determined by phylogenetic analysis. In this study, we focused on the prevalence and genetic variations of the non-structural protein 4 (NSP4) from PRRSV-2 over the past 20 years in China. The fundamental biological properties of the NSP4 were predicted, and an analysis and comparison of NSP4 homology at the nucleotide and amino acid levels was conducted using 123 PRRSV-2 strains. The predicted molecular weight of the NSP4 protein was determined to be 21.1 kDa, and it was predicted to be a stable hydrophobic protein that lacks a signal peptide. NSP4 from different strains exhibited a high degree of amino acid (85.8-100%) and nucleotide sequence homology (81.0-100%). Multiple amino acid substitutions were identified in NSP4 among 15 representative PRRSV-2 strains. Phylogenetic analysis showed that the lineage 8 and 1 strains, the most prevalent strains in China, were indifferent clades with a long genetic distance. This analysis will help fully elucidate the parameters of the PRRSV NSP4 epidemic in China to lay a foundation for adequate understanding of the function of NSP4. Genetic information results from the accumulation of conserved and non-conserved sequences. The high conservation of the NSP4 gene determines the most basic life traits and functions of PRRSV. Analyzing the spatial structure of NSP4 protein and studying the genetic evolution of NSP4 not only provide the theoretical basis for how NSP4 participates in the regulation of the innate response of the host but also provide a target for genetic manipulation and a reasonable target molecule and structure for new drug molecules.

MEIS2C and MEIS2D promote tumor progression via Wnt/ß-catenin and hippo/YAP signaling in hepatocellular carcinoma.

BACKGROUND: MEIS2 has been identified as one of the key transcription factors in the gene regulatory network in the development and pathogenesis of human cancers. Our study aims to identify the regulatory mechanisms of MEIS2 in hepatocellular carcinoma (HCC), which could be targeted to develop new therapeutic strategies. METHODS: The variation of MEIS2 levels were assayed in a cohort of HCC patients. The proliferation, clone-formation, migration, and invasion abilities of HCC cells were measured to analyze the effects of MEIS2C and MEIS2D (MEIS2C/D) knockdown with small hairpin RNAs in vitro and in vivo. Chromatin immunoprecipitation (ChIP) was performed to identify MEIS2 binding site. Immunoprecipitation and immunofluorescence assays were employed to detect proteins regulated by MEIS2. RESULTS: The expression of MEIS2C/D was increased in the HCC specimens when compared with the adjacent noncancerous liver (ANL) tissues. Moreover, MEIS2C/D expression negatively correlated with the prognosis of HCC patients. On the other hand, knockdown of MEIS2C/D could inhibit proliferation and diminish migration and invasion of hepatoma cells in vitro and in vivo. Mechanistically, MESI2C activated Wnt/ß-catenin pathway in cooperation with Parafibromin (CDC73), while MEIS2D suppressed Hippo pathway by promoting YAP nuclear translocation via miR-1307-3p/LATS1 axis. Notably, CDC73 could directly either interact with MEIS2C/ß-catenin or MEIS2D/YAP complex, depending on its tyrosine-phosphorylation status. CONCLUSIONS: Our studies indicate that MEISC/D promote HCC development via Wnt/ß-catenin and Hippo/YAP signaling pathways, highlighting the complex molecular network of MEIS2C/D in HCC pathogenesis. These results suggest that MEISC/D may serve as a potential novel therapeutic target for HCC.

Prognostic value of EGFR and KRAS in resected non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: The prognostic value of EGFR and KRAS mutations in resected non-small cell lung cancer (NSCLC) has been reported. However, conflicting results were reported in these studies. The effect of mutations in these two genes in resected NSCLC remains controversial. METHODS: We searched Internet databases for studies reporting disease-free survival (DFS) and overall survival (OS) in resected NSCLC patients with EGFR or KRAS mutations. A meta-analysis calculating the pooled hazard ratio (HR) for DFS and OS was used to measure the association of EGFR or KRAS mutations with the prognosis of patients after surgery. RESULTS: A total of 9,635 patients from 32 studies were included in this analysis. The combined HR for EGFR mutations on DFS was 0.77 (95% CI 0.66-0.90, p=0.001) and on OS was 0.72 (95% CI 0.66-0.80, p<0.00001). In addition, the combined HR for KRAS mutations on DFS was 1.5 (95% CI 1.15-1.96, p=0.002) and on OS was 1.49 (95% CI 1.28-1.73, p<0.00001). Sensitivity analysis, subgroup analysis, and bias analysis proved the stability of the results. CONCLUSION: The analysis showed that EGFR mutations were significantly associated with DFS and OS. These findings indicated that surgically treated NSCLC patients with EGFR mutations were inclined to exhibit a prolonged DFS and OS. In addition, the results indicated that KRAS mutations predicted worse DFS and OS in patients with resected NSCLC.

Identifying key regulating miRNAs in hepatocellular carcinomas by an omics' method.

The miRNAs play important regulating roles in the pathogenesis of hepatocellular carcinoma (HCC). To uncover key regulating miRNAs in HCC that were neglected by traditional analyzing methods of transcriptomics data, we proposed a novel molecular-network-based omics' (MNBO) method. With this method, we predicted HCC-regulating miRNAs, and confirmed the role of a novel miR-590-3P/EED axis by a clinical study and in vitro, in vivo wet-experiments. The miR-590-3P is significantly down-regulated in HCC patients. And low level of miR-590-3P in HCC is associated with poor prognosis of patients. In HCC cell lines, the miR-590-3P suppressed cell proliferation by inhibiting the transformation G1 phase to S phases of the cell cycle. Moreover, the miR-590-3P inhibited migration and invasion of HCC cells. Further investigations indicated that miR-590-3P play its roles by inhibiting polycomb protein EED. The experiments in animal model implied miR-590-3P could be a potential therapeutic agent for HCC in the future. In conclusion, the discovery of miR-590-3P revealed the MNBO would be a useful strategy to uncover key regulating miRNAs in HCC.

Precision medicine for hepatocellular carcinoma: driver mutations and targeted therapy.

Hepatocellular carcinoma (HCC) is the third most frequent cause of tumor-related mortality and there are an estimated approximately 850,000 new cases annually. Most HCC patients are diagnosed at middle or advanced stage, losing the opportunity of surgery. The development of HCC is promoted by accumulated diverse genetic mutations, which confer selective growth advantages to tumor cells and are called "driver mutations". The discovery of driver mutations provides a novel precision medicine strategy for late stage HCC, called targeted therapy. In this review, we summarized currently discovered driver mutations and corresponding signaling pathways, made an overview of identification methods of driver mutations and genes, and classified targeted drugs for HCC. The knowledge of mutational landscape deepen our understanding of carcinogenesis and promise future precision medicine for HCC patients.

Driver genes in non-small cell lung cancer: Characteristics, detection methods, and targeted therapies.

Lung cancer is one of the most common causes of cancer-related death in the world. The large number of lung cancer cases is non-small cell lung cancer (NSCLC), which approximately accounting for 75% of lung cancer. Over the past years, our comprehensive knowledge about the molecular biology of NSCLC has been rapidly enriching, which has promoted the discovery of driver genes in NSCLC and directed FDA-approved targeted therapies. Of course, the targeted therapies based on driver genes provide a more exact option for advanced non-small cell lung cancer, improving the survival rate of patients. Now, we will review the landscape of driver genes in NSCLC including the characteristics, detection methods, the application of target therapy and challenges.