RESUMEN
Cervical cancer is the leading cause of cancer-related death among women worldwide. Identifying an effective treatment with fewer side effects is imperative, because all of the current treatments have unique disadvantages. Aldo-keto reductase family 1 member B1 (AKR1B1) is highly expressed in various cancers and is associated with tumor development, but has not been studied in cervical cancer. In the current study, we used CRISPR/Cas9 technology to establish a stable HeLa cell line with AKR1B1 knockout. In vitro, AKR1B1 knockout inhibited the proliferation, migration and invasion of HeLa cells, providing evidence that AKR1B1 is an innovative therapeutic target. Notably, the clinically used epalrestat, an inhibitor of aldose reductases, including AKR1B1, had the same effect as AKR1B1 knockout on HeLa cells. This result suggests that epalrestat could be used in the clinical treatment of cervical cancer, a prospect that undoubtedly requires further research. Moreover, aiming to determine the underlying regulatory mechanism of AKR1B1, we screened a series of differentially regulated genes (DEGs) by RNA sequencing and verified selected DEGs by quantitative RT-PCR. In addition, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the DEGs revealed a correlation between AKR1B1 and cancer. In summary, epalrestat inhibits the progression of cervical cancer by inhibiting AKR1B1, and thus may be a new drug for the clinical treatment of cervical cancer.
Asunto(s)
Aldehído Reductasa/fisiología , Inhibidores Enzimáticos/farmacología , Proteínas de Neoplasias/fisiología , Rodanina/análogos & derivados , Tiazolidinas/farmacología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Aldehído Reductasa/antagonistas & inhibidores , Aldehído Reductasa/genética , División Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Ontología de Genes , Células HeLa , Humanos , Invasividad Neoplásica , Proteínas de Neoplasias/antagonistas & inhibidores , Proteínas de Neoplasias/genética , ARN Guía de Kinetoplastida/genética , ARN Guía de Kinetoplastida/farmacología , Rodanina/farmacología , Ensayo de Tumor de Célula Madre , Neoplasias del Cuello Uterino/patologíaRESUMEN
Long noncoding RNAs (lncRNAs) participate in a variety of biological processes and diseases. However, the expression and function of lncRNAs after spinal cord injury has not been extensively analyzed. In this study of right side hemisection of the spinal cord at T10, we detected the expression of lncRNAs in the proximal tissue of T10 lamina at different time points and found 445 lncRNAs and 6522 mRNA were differentially expressed. We divided the differentially expressed lncRNAs into 26 expression trends and analyzed Profile 25 and Profile 2, the two expression trends with the most significant difference. Our results showed that the expression of 68 lncRNAs in Profile 25 rose first and remained high 3 days post-injury. There were 387 mRNAs co-expressed with the 68 lncRNAs in Profile 25. The co-expression network showed that the co-expressed genes were mainly enriched in cell division, inflammatory response, FcγR-mediated cell phagocytosis signaling pathway, cell cycle and apoptosis. The expression of 56 lncRNAs in Profile2 first declined and remained low after 3 days post-injury. There were 387 mRNAs co-expressed with the 56 lncRNAs in Profile 2. The co-expression network showed that the co-expressed genes were mainly enriched in the chemical synaptic transmission process and in the signaling pathway of neuroactive ligand-receptor interaction. The results provided the expression and regulatory network of the main lncRNAs after spinal cord injury and clarified their co-expressed gene enriched biological processes and signaling pathways. These findings provide a new direction for the clinical treatment of spinal cord injury.