Inhibitor of growth 4 inhibits cell proliferation,migration, and induces apoptosis of renal cell carcinoma cells

The inhibitor of growth 4 (ING4) is known as a tumor suppressor. The expressions of ING4 were markedly reduced in human renal clear cell carcinoma (ccRCC) tissues. However, the role of ING4 in renal cell carcinoma (RCC) remains unknown. The aim of the current study was to detect the ING4 expression level and its potential role in human RCC cell lines. Our results showed that ING4 was lowly expressed in human RCC cell lines compared with that in proximal tubular cell line. Ectopic overexpression of ING4 inhibited the proliferation, migration, and invasion properties, and as well as prevented epithelial-mesenchymal transition (EMT) phenotype of RCC cells. In addition, ING4 overexpression induced cell apoptosis and autophagy in RCC cells. Furthermore, ING4 overexpression suppressed the activation of PI3K/Akt pathway in RCC cells. The activator of PI3K/Akt, insulin-like growth factor 1, abolished the effects of ING4 on RCC cells. These findings indicated that ING4 presented anticancer activity in RCC cells. The effects of ING4 on RCC cells were mediated by regulating the PI3K/Akt pathway. These findings suggested that ING4 could be used for gene therapy of RCC.     

Transient receptor potential melastatin 2–antisense RNA is overexpresed in osteosarcoma and regulates cell proliferation and apoptosis

Accumulating evidence suggested that transient receptor potential melastatin 2–antisense RNA (TRPM2-AS) played crucial roles in the progression of human cancers. However, the role of TRPM2-AS was still unknown in osteosarcoma. The aim of this study was to explore the clinical significance of TRPM2-AS in osteosarcoma patients, and determine the role of TRPM2-AS on osteosarcoma cell proliferation and apoptosis. In our results, we identified a novel oncogenic long noncoding RNA TRPM2-AS, which was overexpressed in osteosarcoma tissues and cells, and correlated with advanced Enneking stage, large tumor size and high histological grade in osteosarcoma cases. Survival analysis indicated that osteosarcoma patients with high TRPM2-AS expression had an obviously shorter overall survival time than those with low TRPM2-AS expression. Loss-of-function studies suggested that suppression of TRPM2-AS expression inhibited osteosarcoma cell proliferation and induced cell apoptosis through upregulating cleaved caspase-3 and cleaved caspase-9 expression. In conclusion, TRPM2-AS acts as an oncogenic long noncoding RNA and predicts poor prognosis in osteosarcoma.     

转谷氨酰胺酶2抑制H1亚型流感病毒在MDCK细胞中的增殖

组织转谷酰胺酶(transglutaminase 2,TGM2)是一种普遍存在的多功能蛋白,与不同细胞的粘附和肿瘤形成有关.有证据表明,TGM2参与了宿主细胞与病毒间的相互作用,但是对于流感病毒在细胞内增殖的影响还未有报道.为了探究MDCK细胞中TGM2对H1N1亚型流感病毒增殖的影响,本研究构建了TGM2过表达和敲除...     

Marine biological injuries and their medical management: A narrative review

The marine environment can be extremely dangerous, and the harm caused by marine organisms when they contact the human body can be especially harmful, even deadly. Contact includes stings, bites, wounds, and consumption as food. In this article, the characteristics of the common marine biological injuries are summarized, the major marine organisms causing damage in China’s marine waters are described, and injury prevention and treatment methods are discussed.     

Epac‐2 ameliorates spontaneous colitis in Il‐10 −/− mice by protecting the intestinal barrier and suppressing NF‐κB/MAPK signalling

Intestinal barrier dysfunction and intestinal inflammation interact in the progression of Crohn''s disease (CD). A recent study indicated that Epac‐2 protected the intestinal barrier and had anti‐inflammatory effects. The present study examined the function of Epac‐2 in CD‐like colitis. Interleukin‐10 gene knockout (Il‐10 ^−/−) mice exhibit significant spontaneous enteritis and were used as the CD model. These mice were treated with Epac‐2 agonists (Me‐cAMP) or Epac‐2 antagonists (HJC‐0350) or were fed normally (control), and colitis and intestinal barrier structure and function were compared. A Caco‐2 and RAW 264.7 cell co‐culture system were used to analyse the effects of Epac‐2 on the cross‐talk between intestinal epithelial cells and inflammatory cells. Epac‐2 activation significantly ameliorated colitis in mice, which was indicated by reductions in the colitis inflammation score, the expression of inflammatory factors and intestinal permeability. Epac‐2 activation also decreased Caco‐2 cell permeability in an LPS‐induced cell co‐culture system. Epac‐2 activation significantly suppressed nuclear factor (NF)‐κB/mitogen‐activated protein kinase (MAPK) signalling in vivo and in vitro. Epac‐2 may be a therapeutic target for CD based on its anti‐inflammatory functions and protective effects on the intestinal barrier.     

EIF1A depletion restrains human pituitary adenoma progression

EIF1A encodes a translation initiation factor in eukaryocyte and aberrant expression of EIF1A is deemed to be associated with dysfunctions in intracranial diseases. The goal of this research was to explore the impacts of EIF1A on progression of human pituitary adenoma (PA). We employed immunohistochemistry to assess the expression of EIF1A in PA and para-carcinoma tissues. After constructing EIF1A-knockdown cell models via lentivirus infection, we examined cell proliferation through CCK-8 assay and Celigo cell counting assay. Flow cytometry was utilized to detect cell apoptosis and the migration ability of experimental cells was estimated using wound-healing assay and Transwell assay. The activity of the apoptosis-related factor, Caspase 3, was also examined via Caspase 3 activity assay. Lastly, in vivo xenograft mouse models were established to verify findings derived from in vitro cell models. Our results affirmed upregulation of EIF1A in PA cells and revealed that depletion of EIF1A could seriously limit cell proliferation and weaken the capacity of cell migration, and also enhance apoptosis of tumor cells. Mechanistically, degradation in cell growth mediated by EIF1A knockdown may involve in activation of MAPK signaling but inactivation of PI3K/AKT signaling pathway. This study indicates EIF1A plays a prominent role in facilitating tumor cell proliferation and migration which may further contribute to PA progression.Key words: EIF1A, Pituitary adenoma, Cell proliferation, Cell migration, MAPK     

基于RNA-seq技术对乌头属铁棒锤中自交不亲和S基因的挖掘与分析

以毛茛科乌头属铁棒锤 (Aconitum pendulum N. Busch)2个品系‘蓝花铁棒锤’(‘WSYB1’)和‘黄花铁棒锤’(‘WSYY1’)为材料, 对其进行转录组测序(RNA-seq), 采用生物信息学方法鉴定其中可能存在的花柱S基因(self-incompatibility gene)和花粉S基因, 并...     

Genome‐scale screening in a rat haploid system identifies Thop1 as a modulator of pluripotency exit

ObjectivesThe rats are crucial animal models for the basic medical researches. Rat embryonic stem cells (ESCs), which are widely studied, can self‐renew and exhibit pluripotency in long‐term culture, but the mechanism underlying how they exit pluripotency remains obscure. To investigate the key modulators on pluripotency exiting in rat ESCs, we perform genome‐wide screening using a unique rat haploid system.Materials and MethodsRat haploid ESCs (haESCs) enable advances in the discovery of unknown functional genes owing to their homozygous and pluripotent characteristics. REX1 is a sensitive marker for the naïve pluripotency that is often utilized to monitor pluripotency exit, thus rat haESCs carrying a Rex1‐GFP reporter are used for genetic screening. Genome‐wide mutations are introduced into the genomes of rat Rex1‐GFP haESCs via piggyBac transposon, and differentiation‐retarded mutants are obtained after random differentiation selection. The exact mutations are elucidated by high‐throughput sequencing and bioinformatic analysis. The role of candidate mutation is validated in rat ESCs by knockout and overexpression experiments, and the phosphorylation of ERK1/2 (p‐ERK1/2) is determined by western blotting.ResultsHigh‐throughput sequencing analysis reveals numerous insertions related to various pathways affecting random differentiation. Thereafter, deletion of Thop1 (one candidate gene in the screened list) arrests the differentiation of rat ESCs by inhibiting the p‐ERK1/2, whereas overexpression of Thop1 promotes rat ESCs to exit from pluripotency.ConclusionsOur findings provide an ideal tool to study functional genomics in rats: a homozygous haploid system carrying a pluripotency reporter that facilitates robust discovery of the mechanisms involved in the self‐renewal or pluripotency of rat ESCs.

Differentiation of pluripotent rat embryonic stem cells (ESCs) in vitro is difficult to achieve for unknown mechanisms. Rat haploid ESCs (haESCs) have been validated as a powerful tool to target unknown functional genes and pathways based on homozygous genetic screening. Xu et al. utilized Rex1‐GFP labelled‐rat haESCs to conduct genome‐scale screening of genes modulating pluripotency exiting. Validation experiments showed that Thop1 (one of the screened out genes) played very important roles in the random differentiation of rat ESCs in vitro via modulating phosphorylation of ERK.