ABSTRACT
Abstract Background: CTHRC1 is highly expressed in various cancers. Objectives: The aim of the study was to study the role of CTHRC1 played in lung adenocarcinoma (LUAD) development and its underlying biological functions. Methods: Enriched pathways and upstream transcription factors of CTHRC1 were explored by bioinformatics analysis. Dual-luciferase assay and Chromatin immunoprecipitation assay were used to verify the binding relationship between CTHRC1 and HOXB9. CCK-8 was utilized to detect cell viability. Expression levels of CTHRC1, HOXB9, and angiogenesis-related genes were assessed by quantitative real time-polymerase chain reaction. Angiogenesis assay was used to detect angiogenesis ability. Quantitative analysis of metabolites were used to detect the accumulation of neutral lipids, the levels of free fatty acids (FAs), and glycerol. Western blot was conducted to measure expression of metabolic enzymes of FA. Results: CTHRC1 was enriched in FA metabolic pathway, which was positively correlated and bound with HOXB9. CTHRC1 and HOXB9 expression was remarkably up-regulated in LUAD cells. Overexpression of CTHRC1 promoted FA metabolic pathway and angiogenesis, and FA inhibitor Orlistat restored it to NC group level. Meanwhile, CTHRC1 affected LUAD angiogenesis by activating HOXB9 to regulate FA metabolism. Conclusions: This study found that activation of CTHRC1 by HOXB9 induces angiogenesis by mediating FA metabolism. CTHRC1 may be a potential target for LUAD diagnosis.
ABSTRACT
The Homeobox B9 (HOXB9) is a homeodomain-containing transcription factor that participates in the progression of various malignancies. Nevertheless, the functional role of HOXB9 in prostate cancer cells is largelyunknown. Hence, we aimed to address the effect of HOXB9 on the progression of prostate cancer cells. Smallinterfering RNA (siRNA) against HOXB9 was used to downregulate HOXB9 expression in PC3 and DU145cells. Western blotting was performed to detect the expression levels of HOXB9 and other related proteins. Cellproliferation was tested by the Cell Counting Kit-8 (CCK-8) and cell cycle and apoptosis were investigated byflow cytometry. Angiogenesis was examined using tube formation assays The Transwell assays were carriedout to assess the migratory and invasive capacities of cells. Here, we found that HOXB9 knockdown significantly reduced cell proliferation via inducing cell cycle arrest at G1 phase. This treatment also reducedangiogenesis, migration and invasion abilities of PC3 and DU145 cells in vitro. We also found that HOXB9knockdown inhibits the activation of the PI3K/AKT signaling pathway in prostate cancer cells. In conclusion,our findings revealed that HOXB9 promotes prostate cancer progression and might be a novel and effectivetherapeutic target for human prostate cancer.
ABSTRACT
Preoperative chemo- and radiotherapeutic strategies followed by surgery are currently a standard approach for treating locally advanced gastric and esophagogastric junction cancer in Western countries. However, in a large number of cases, the tumor is extremely resistant to these treatments and the patients are exposed to unnecessary toxicity and delayed surgical therapy. The current clinical trials evaluating the combination of preoperative systemic therapies with modern targeted and immunotherapeutic agents represent a unique opportunity for identifying predictive biomarkers of response to select patients that would benefit the most from these treatments. However, it is of utmost importance that these potential biomarkers are corroborated by extensive preclinical and translational research. The aim of this review article is to present the most promising biomarkers of response to classic chemotherapeutic, anti-HER2, antiangiogenic, and immunotherapeutic agents that can be potentially useful for personalized preoperative systemic therapies in gastric cancer patients.