RESUMEN
BACKGROUND: This Study investigated the role of WWTR1-AS1 in cervical squamous cell carcinoma (CSCC). RESULTS: WWTR1-AS1 expression was upregulated in CSCC tissues. WWTR1-AS1 was predicted to interact with miR-136, whereas correlation analysis revealed that there was no close correlation between WWTR1-AS1 and miR-136 across CSCC samples. Moreover, WWTR1-AS1 and miR-136 did not regulate the expression of each other. In addition, overexpression of WWTR1-AS1 increased the expression levels of Notch3, which could be targeted by miR-136. Cell stemness analysis indicated that the overexpression of WWTR1-AS1 and Notch3 increased CSCC cell stemness and the capacity of CSCC cell to grow as spheroids. Overexpression of miR-136 decreased CSCC cell stemness and reversed the effects of overexpression of WWTR1-AS1 on Notch3 in CSCC cells. CONCLUSION: Therefore, WWTR1-AS1 may upregulate Notch3 through miR-136 to increase cancer cell stemness in CSCC.
Asunto(s)
Carcinoma de Células Escamosas , MicroARNs , ARN Largo no Codificante , Neoplasias del Cuello Uterino , Femenino , Humanos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , MicroARNs/genética , ARN Largo no Codificante/genética , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ , Neoplasias del Cuello Uterino/patología , ARN sin Sentido/genéticaRESUMEN
N,N'-Dinitrosopiperazine (DNP) induces nasopharyngeal carcinoma (NPC) and shows organ specificity to the nasopharyngeal epithelium. To investigate its mechanism, the rat NPC model was induced using DNP. Rat NPC and normal nasopharyngeal cells were obtained from the NPC model using laser capture. The total proteins from these cell samples were separated with two-dimension polyacrylamide gel electrophoresis techniques, and highly expressed proteins (> five-fold) were analyzed using matrix-assisted laser desorption/ionization time of flight and bioinformatics. The results showed that HSP70 and mucin 5B expression increased not only in rat NPC but also in atypical hyperplasia nasopharyngeal tissues, a precancer stage of NPC. High-expression of heat shock protein 70 (HSP70) and mucin 5B was further supported by western blot analysis. The immunofluorescence and western-blotting studies further showed that DNP induced the expression of HSP70 and mucin 5B in a dosage-dependent manner in normal nasopharyngeal epithelia cells. Our data indicate that DNP triggers over-expression of HSP70 and mucin 5B, and is involved in nasopharyngeal tumorigenesis. HSP70 and mucin 5B may be important targets in nasopharyngeal tumorigenesis induced by DNP.
