The Expression Of SIRT7 In Actinic Keratosis And The Mechanism Of Its Involvement In The Disease

Background and Objective:Actinic keratosis(AKs)is a kind of common skin disease,which has the potential to transform into skin squamous cell carcinoma.SIRT7,one of the Silent information regulator family members,which was found to be abnormally expressed in many malignant tumors,such as cervical squamous cell carcinoma.However,the expression and specific biological function of SIRT7 in the actinic keratosis remain unclear.mTOR is a downstream regulator of SIRT7.This sdudy explored the correlation between SIRT7 and AKs skin diseases,and further proved the mechanism of SIRT7 and related mTOR signaling pathway in actinic keratosis.Methods:In this study,89 cases of AKs and 28 cases of adjacent tissues of AKs from Shanghai Fengxian district central hospital were statistically analyzed to obtain the epidemiological information of AKs,and the pathological features and grading were analyzed by pathological sections.In addition,this study took SIRT7 as the research object,and determined the expression of SIRT7 in the skin lesions of AKs patients by immunohistochemical method,so as to compare the difference in SIRT7 expression between normal skin and the AKs skin,and make correlation analysis with pathological features.The transcription and expression levels of SIRT7 in normal and AKs tissues were determined by RT-PCR and Western blot,and the expression levels of SIRT7 and mTOR in primary cells and HT297.T cells were compared,so as to explore the role of SIRT7 and its associated mTOR signaling pathway in AKs diseases.Results:There was a significant difference between 58 male patients(61.16%)and 37 female patients(38.84%)of AKs patients,and the male to female ratio(1.8:1).Patients with AKs were more likely to be found on the face(76.52%).And the positive expression rate of SIRT7 protein was 75.28%(67/89)in the skin lesions of 89 cases of AKs.In the immunohistochemical results of 28 cases of normal skin adjacent to AKs,the positive expression rate of SIRT7 protein was 7.15%(2/28),and the positive expression rate of SIRT7 protein in AKs was higher than that in normal skin,the difference between the two groups was significant and statistically significant(p<0.0001).In addition,the expression level and positive rate of SIRT7 were significantly increased with the increase of pathological classification.SIRT7 expression level and positive rate were significantly increased between AKs ?,? and ? groups,and the expression level was statistically different(P<0.05).The results of functional studies on SIRT7 in AKs disease show that SIRT7 was positively correlated with AKs disease.In AKs,the up-regulation of SIRT7 was associated with the expression of mTORC1 signal.Cell experiments also proved that SIRT7 regulates keratinocytes proliferation through mTORC1 signal.Conclusion:The positive rate of SIRT7 expression in the skin of patients with actinic keratosis was significantly increased,which was closely related to the severity of actinic keratosis,suggesting that SIRT7 may play a major role in the occurrence or progression of AKs disease,and may be a potential target for the diagnosis and even treatment of actinic keratosis.