HOXB13 promotes gastric cancer cell migration and invasion via IGF-1R upregulation and subsequent activation of PI3K/AKT/mTOR signaling pathway.

This study aimed at exploring HOXB13 expression and function in gastric cancer (GC), and the underlying molecular mechanism. HOXB13 and fat mass and obesity-associated protein (FTO) expression in GC and non-GC tissues of GC patients were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) and verified by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blotting. The regulatory relationship between FTO and HOXB13 was verified via RT-qPCR, methylated RNA immunoprecipitation sequencing (MeRIP-seq), and double luciferase reporter gene assay. The effects of HOXB13 and FTO on proliferation, invasion, and migration of GC cells were studied using EdU and Transwell assays. HOXB13 and FTO expression was abnormally high in GC tissues and cell lines, with no significant correlation between HOXB13 and FTO expression and the prognosis of GC patients. Inhibiting FTO expression in GC cells decreased HOXB13 methylation and upregulated HOXB13 expression. Inhibiting HOXB13 and FTO expression suppressed GC cell proliferation, migration, and invasion. Decreased HOXB13 expression suppressed PI3K/AKT/mTOR signaling pathway activity, while atypical HOXB13 expression promoted it. A probable downstream target of HOXB13 was insulin-like growth factor 1 receptor (IGF-1R); a decrease in IGF-1R relieved GC cell migration, invasion, and proliferation and inhibited PI3K/AKT/mTOR signaling pathway activity promoted by atypical HOXB13 expression. HOXB13 and FTO expression is elevated in GC. FTO suppresses HOXB13 methylation; FTO and HOXB13 expression promotes GC cell proliferation, migration, and invasion. HOXB13 expression intensifies GC invasion through PI3K/AKT/mTOR signaling via IGF-1R. HOXB13 and associated signaling pathways can be effective targets for GC therapy.

Guo C ，Chu H ，Gong Z ，Zhang B ，Li C ，Chen J ，Huang L ... -  《-》

NUCKS1 promotes gastric cancer cell aggressiveness by upregulating IGF-1R and subsequently activating the PI3K/Akt/mTOR signaling pathway.

The effects of nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1) on tumor cells and the relevant mechanisms are less well defined. This study aimed to explore the role and mechanism of action of NUCKS1 in gastric cancer (GC) progression. The expression dynamics of NUCKS1 were examined using microarray-based immunohistochemistry (IHC) in a group of carcinomatous and adjacent non-tumor specimens. Various in vitro and in vivo assays were performed to clarify the function of NUCKS1 in GC and its underlying mechanisms. In our research, NUCKS1 overexpression was identified by IHC in 86/200 (43%) GC patients, was significantly related to the invasive phenotype of GC and was an indisputable predictor of shortened survival. Depleting NUCKS1 in GC cells significantly induced apoptosis and reduced cell proliferation and invasiveness in vitro and inhibited tumor growth in vivo. Additionally, ectopic overexpression of NUCKS1 in GC cells enhanced proliferation and invasion in vitro and promoted tumor growth in vivo. Importantly, PI3K/Akt/mTOR signaling pathway activity was inhibited upon downregulation of NUCKS1 expression and enhanced by ectopic overexpression of NUCKS1. Subsequently, the insulin-like growth factor 1 receptor (IGF-1R) gene was found to be a potential downstream target of NUCKS1 in GC cells, and knockdown of IGF-1R eliminated the augmentation of GC cell migration, invasion and proliferation as well as PI3K/Akt/mTOR signaling pathway activity by ectopic NUCKS1. The data suggested that NUCKS1 enhanced GC aggressiveness via the PI3K/Akt/mTOR signaling pathway in an IGF-1R-dependent manner. NUCKS1 or its respective signaling pathways could hold immense promise as potent anticancer targets for GC treatment.

Huang YK ，Kang WM ，Ma ZQ ，Liu YQ ，Zhou L ，Yu JC ... -  《-》

Ropivacaine suppresses tumor biological characteristics of human hepatocellular carcinoma via inhibiting IGF-1R/PI3K/AKT/mTOR signaling axis.

Zhang R ，Lian Y ，Xie K ，Cai Y ，Pan Y ，Zhu Y ... -  《-》

[Kuwanon G inhibits growth, migration and invasion of gastric cancer cells by regulating the PI3K/AKT/mTOR pathway].

Geng Z ，Yang J ，Niu M ，Liu X ，Shi J ，Liu Y ，Yao X ，Zhang Y ，Zhang X ，Hu J ... -  《-》

Circular RNA hsa_circ_0010882 promotes the progression of gastric cancer via regulation of the PI3K/Akt/mTOR signaling pathway.

Peng YK ，Pu K ，Su HX ，Zhang J ，Zheng Y ，Ji R ，Guo QH ，Wang YP ，Guan QL ，Zhou YN ... -  《-》