Background Emerging studies have shown that HOTAIR acts as an oncogene in gastric cancer (GC). However, its role in the extracellular matrix and in tumor immune infiltration remains unknown. Methods HOTAIR and COL5A1 levels were analyzed by bioinformatics analysis and validated by qRT-PCR, western blotting and immunohistochemistry assays. The regulatory relationships between components of the HOTAIR/miR-1277-5p/ COL5A1 axis and the role of this axis in GC were predicted by bioinformatics analysis, and validated by in vitro and in vivo experiments. The correlation between COL5A1 and GC immune infiltration was assessed by bioinformatics analysis and a COL5A1-based predictive nomogram was established using the Stomach Adenocarcinoma dataset from The Cancer Genome Atlas. Results We found that HOTAIR and COL5A1 were overexpressed in GC compared to normal controls, which predicted poor prognosis. The regulatory relationship of the HOTAIR/miR-1277-5p/COL5A1 axis in GC was demonstrated, and HOTAIR and COL5A1 were found to promote GC growth while miR-1277-5p exerted the reverse effects. In addition, COL5A1 was negatively associated with tumor purity but positively associated with immune infiltration, which suggested that COL5A1mediated GC growth may be partially mediated by the regulation of immune infiltration. Additionally, the established COL5A1-based nomogram showed that COL5A1 can serve as a prognostic biomarker in GC. Conclusions HOTAIR regulates GC growth by sponging miR-1277-5p and upregulating COL5A1, and COL5A1-mediated GC cell proliferation may be mediated by effects on the tumor microenvironment, which provides novel targets for GC treatment.
Transient receptor potential polycystic 2 (TRPP2) exerts vital roles in various types of cancer; however, its underlying mechanisms remain largely unknown. This study is aimed at investigating whether knockdown of TRPP2 affected the AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling pathway and the proliferation of HN-4, cell line originating from human oral and hypopharyngeal squamous cell carcinoma. In addition, the interactions among AMPK/ACC, AMPK/protein kinase RNA-like endoplasmic reticulum kinase (PERK)/eukaryotic initiation factor 2α (eIF2α) and TRPP2/PERK/eIF2α signaling pathways, and their association with cell proliferation were also explored. The results showed that the relative expression levels of phosphorylated (p)-ACC, p-PERK, and p-eIF2α in HN-4 cells were significantly increased following treatment with 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) and significantly decreased in cells treated with compound C. Therefore, consistent with previous studies, the AMPK/ACC and AMPK/PERK/eIF2α signaling pathways were upregulated and downregulated following treatment with an AMPK agonist and inhibitor, respectively. Furthermore, TRPP2 knockdown decreased p-PERK and p-eIF2α expression levels and increased those of p-AMPK and p-ACC. Additionally, knockdown of TRPP2 increased HN-4 cell proliferation, while treatment with an AMPK inhibitor or agonist increased or inhibited TRPP2-specific siRNA-mediated cell proliferation, respectively. In conclusion, silencing of TRPP2 expression increased HN-4 cell proliferation via inhibiting the PERK/eIF2α signaling pathway, while the AMPK/ACC signaling pathway was possibly activated by a feedback mechanism to reduce enhanced cell proliferation.
Background The incidence of prostate cancer (PCa) increases with age, and age and tumor microenvironment (TME) have important roles in the development of PCa, while the underlying mechanisms have not been fully elucidated. Materials and method The Cancer Genome Atlas‐Prostate Adenocarcinoma (TCGA‐PRAD) RNA‐Seq, the Surveillance, Epidemiology, and End Results (SEER‐PRAD), and ESTIMATE data were downloaded, and the clinical information of PRAD patients in our cohort was collected. The associations among age, TME, and PCa were analyzed. The age‐ and TME‐related risk score (ATRS) of each TCGA‐PRAD sample was calculated based on the identified age‐ and TME‐related differentially expressed genes (DEGs), and the correlation of ATRS with immune‐related characteristics of PCa patients was analyzed, and the ATRS‐based overall survival (OS)‐predicting nomogram was also established. Results Age was correlated with OS, PSA level, tumor stage, T stage, N stage, Gleason score, nerve invasion of PCa, and age was positively correlated with stromal, immune, and ESTIMATE scores. The compositions of immune cells of TCGA‐PRAD patients altered with age. Nine age‐ and TME‐related prognostic DEGs were identified, and the ATRS of each TCGA‐PRAD patient was calculated based on the identified nine DEGs. The ATRS was associated with the expression of immune checkpoints and intratumoral cytolytic activity, and the ATRS‐based nomogram performed well in predicting the outcomes of PCa patients. Conclusions Age and TME had crucial roles in PCa, and the ATRS gene signature was associated with the immune‐related characteristics of PCa patients, which showed good performance in predicting OS of PCa patients.
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