KIRREL promotes the proliferation of gastric cancer cells and angiogenesis through the PI3K/AKT/mTOR pathway.

Anti-angiogenesis is a promising therapeutic strategy for delaying tumour progression that offers, new hope for gastric cancer targeted therapy. The purpose of this study was to investigate the precise mechanism by which Kin of IRRE-like protein 1 (KIRREL) contributes to the development of gastric cancer, particularly in terms of tumour angiogenesis. Differential expression of KIRREL in tissues and cells was detected using quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. A bioinformatics analysis was conducted to screen for the function and pathway enrichment of KIRREL in gastric cancer. Lentivirus-induced KIRREL silencing in SNU-5 cells and lentivirus-induced KIRREL overexpression in AGS cells were used to study the effect of KIRREL on the proliferation, cell cycle and angiogenesis of gastric cancer cells. Moreover, the expressions of PI3K, P-PI3K, AKT, P-AKT, mTOR, P-mTOR, HIF-1α and VEGF were also detected. Gastric cancer tissues and cells had high levels of KIRREL expression, which is associated with the proliferation, cell cycle and angiogenesis of gastric cancer cells. After silencing and overexpressing KIRREL in SNU-5 and AGS cells, respectively, the proliferation and angiogenesis of SNU-5 cells were inhibited, while the proliferation and angiogenesis of AGS cells were promoted. According to a bioinformatics analysis of the KIRREL gene, angiogenesis regulation and the PI3K/AKT pathway were highly connected. The PI3K/AKT/mTOR pathway was repressed and stimulated by KIRREL silencing and overexpression, respectively. IGF-1, an AKT agonist, and LY294002, an inhibitor, reversed the effects of KIRREL silencing and overexpression on the PI3K/AKT/mTOR pathway and on gastric cancer cell proliferation and angiogenesis. KIRREL may mediate the proliferation and angiogenesis of gastric cancer cells through the PI3K/AKT/mTOR signalling pathway. These findings could help in the further development of potential anti-angiogenesis targets.

A prognostic model based on the Augmin family genes for LGG patients.

Gliomas are the most prevalent primary tumors in the central nervous system. Despite some breakthroughs in the treatment of glioma in recent years, survival rates remain low. Although genes of the Augmin family play a key role in microtubule nucleation, the role they play in gliomas is unclear. Transcriptome data were extracted from UCSC XENA and GTEx for low-grade glioma (LGG) and normal tissues, respectively. The protein interaction network associated with Augmin family genes was established using STRING and GeneMANIA databases. Enrichment analysis of gene-related functions and pathways was used to explore potential biological pathways and TIMER to assess immune cell infiltration. Regression analysis and Kaplan-Meier analysis were used to look at the clinical characteristics of the Augmin family genes and the association with the prognosis of patients with glioma. The results showed that the mRNA expression of Augmin family genes was significantly elevated in LGG tissues, except for HAUS7. Immunoregulation, cell cycle, apoptosis and other signaling pathways may be involved in the development and progression of LGG. Except for HAUS4 and HAUS7, the expression of all genes was positively correlated with immune cell infiltration. High expression of HAUS1, HAUS3, HAUS5, HAUS7, HAUS8 and low expression of HAUS4, HAUS6 in LGG was associated with poor prognosis. The risk models constructed based on the pivotal genes HAUS2, HAUS4 and HAUS8 were validated by nomogram and confirmed to be clinically useful for predicting the prognosis of LGG.

ATR Inhibitors in Platinum-Resistant Ovarian Cancer.

Platinum-resistant ovarian cancer (PROC) is one of the deadliest types of epithelial ovarian cancer, and it is associated with a poor prognosis as the median overall survival (OS) is less than 12 months. Targeted therapy is a popular emerging treatment method. Several targeted therapies, including those using bevacizumab and poly (ADP-ribose) polymerase inhibitor (PARPi), have been used to treat PROC. Ataxia telangiectasia and RAD3-Related Protein Kinase inhibitors (ATRi) have attracted attention as a promising class of targeted drugs that can regulate the cell cycle and influence homologous recombination (HR) repair. In recent years, many preclinical and clinical studies have demonstrated the efficacy of ATRis in PROC. This review focuses on the anticancer mechanism of ATRis and the progress of research on ATRis for PROC.