Role of PKC ι in the YAP1 signaling pathway in cervical cancer and its relationship with prognosis
Objective To explore the role of protein kinase cι(PKCι/PRKCI)in the yes-associated protein 1(YAP1)signaling pathway in cervical cancer and its relationship with prognosis.Methods Normal cervical tissues(NCTs,n=80),low-grade squamous intraepithelial lesions(LSILs,nr=80),high-grade squamous intraepithelial lesions(HSILs,n=80)and early cervical squamous cell carcinoma(SCC,n=80)were collected during the total hysterectomy from January 2013 to January 2015.Expression levels of PKCι and YAP1 were analyzed by immunohistochemistry(IHC),and their correlation with clinical pathology and prognosis was analyzed.Human cervical cancer SiHa cells were transfected with overexpression plasmid of PKCι,followed by the assessment of transfection efficiency via the observation of fluorescence quantity and intensity using an inverted fluorescence microscope.After the induction of PRKCI inhibitor aurothiomalate,cell viability and migration were measured by CCK-8 and Transwell assay,respectively.Expression level of PRKCI was detected by real-time quantitative reverse-transcription polymerase chain reaction(qRT-PCR),followed by transcriptome sequencing and qRT-PCR for verification.Results There were significant differences in the positive rates of PKCιand YAP1 in NCTs,LSILs,HSILs and SCC(P＜0.05),which were higher in those with a higher pathological grade(P＜0.05).Pathological grade of cervical lesions was positively correlated with both positive expressions of PKCι and YAP1(P＜0.05).Positive expression of PKCι was positively correlated with that of YAP1 in SCC(P＜0.05).There were significant differences in the positive expressions of PKCι and YAP1 in SCC with varying differentiation levels and those either with blood vessel invasions or not(P＜0.05).Univariate analysis in survival analysis of SCC patients showed that protein expressions,differentiation,lymph node metastasis and blood vessel invasion were independent factors for the overall prognosis(P＜0.05).Protein expressions and lymph node metastasis were independent risk factors for the 5-year survival of SCC,and higher protein expressions of PKCι and YAP1 and lymph node metastasis were risk factors(P＜0.05).The expression level of PKCι in SiHa cells transfected with the overexpression plasmid of PKCιwas significantly higher than those transfected with a negative control(P＜0.05).Conclusion Patients with cervical lesions are often accompanied by abnormal expressions of PKCι and YAP1,which may have synergistic effects between each other to affect the occurrence and development of SCC and its prognosis,and promote the proliferation and migration of SCC cells.Our findings provide a possible basis for the pathogenesis study of SCC and its diagnosis,treatment and prediction of the prognosis.
cervical cancerprotein kinase Cιyes-associated protein 1
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