长链非编码RNA-RASA4CP通过MAPK信号通路抑制宫颈癌细胞增殖的作用研究OA

Objective:To investigate the role of long non-coding RNA RASA4CP in the occurrence and development of cervical cancer and its correlation with the MAPK signaling pathway.Methods:RT-qPCR was used to detect the expression levels of RASA4CP in 60 paired cervical cancer tissues and adjacent normal tissues.HeLa cells stably overexpressing RASA4CP were established via lentiviral transduction.Cell proliferation was assessed using the CCK-8 as-say,while apoptosis and cell cycle distribution were analyzed by flow cytometry.Subcellular lo-calization of RASA4CP was determined using RNA fluorescence in situ hybridization.The ex-pression levels of MAPK signaling pathway and apoptosis-related proteins were detected by Western blot.The in vivo inhibitory effect of RASA4CP overexpression on tumor growth was e-valuated using a nude mouse xenograft model,followed by protein expression analysis in tumor tissues.Results:RASA4CP expression was significantly downregulated in cervical cancer tissues compared with adjacent normal tissues(P<0.05),and was also markedly reduced in HPV18-positive HeLa cells compared with immortalized cervical epithelial H8 cells.Overexpression of RASA4CP inhibited HeLa cell viability at 72h(P<0.05),increased the proportion of apoptotic cells(P<0.01),and induced G2/M phase cell cycle arrest(P<0.05).RNA-FISHrevealed that RASA4CP was predominantly localized in the cytoplasm.Western blot results showed that RASA4CP overexpression led to increased phosphorylation levels of p38 and JNK,decreased phosphorylation levels of ERK and AKT,upregulated expression of the pro-apoptotic proteins Bax and cleaved caspase-3,and downregulated expression of the anti-apoptotic proteins Bcl-2 and NF-κB(P<0.05).The nude mouse xenograft assay demonstrated that the RASA4CP over-expression group exhibited significantly smaller tumor volumes and weights compared with the control group(P<0.05),along with decreased expressions of p-AKT,p-ERK,and Bcl-2,and increased expression of p-p38 in tumor tissues.Conclusion:In the HeLa cell model,overexpres-sion of RASA4CP inhibits proliferation,induces apoptosis,and is accompanied by changes in the MAPK pathway,suggesting its potential as a biomarker for HPV18-positive cervical cancer.