The Influencing Factors Of Kaposi's Sarcoma And The Regulation Of MiR-126 On Its Growth

Objective:Kaposi's sarcoma(KS)is also known as multiple idiopathic hemorrhagic sarcoma.In our country,the classical KS mainly occurs in the ethnic minority population of Xinjiang.The pathogenesis is not clear,and the lesions are usually multifocal.There are no standardized guidelines for the treatment of KS.The commonly methods of treatment are radiotherapy,chemotherapy,physical therapy and drug treatment,but the long-term effect is poor and the disease is easy to relapse.Research on the pathogenesis is conducive to the prevention and treatment of diseases.In this study,a case-control study was conducted to analyze the factors of KS.The subjects were patients with classic KS and patients without KS who lived in Xinjiang for a long time.The histology and biological characteristics of KS have always been a hot topic of debate.Some scholars have done a lot of research on the origin of KS,but there is still no unified conclusion.This article systematically reviews the literature,combining on the experimental study,the origin of KS was summarized.Studies on the regulation of the growth of KS can provide molecular basis for targeted therapy.MicroRNA-126(miR-126)is involved in the regulation of tumor growth,which is up-regulated in KS.The target of miR-126 is PI3K.PTEN/PI3K/AKT signaling pathway is a classical pathway to regulate cell growth and apoptosis.The aim of this study was to investigate the regulation of miR-126 on the signal pathway in vitro;find the target molecule for the treatment of KS;investigate the expression of PTEN/PI3K/AKT signaling pathway members PTEN,P-PTEN,AKT,P-AKT,PDK in the tissues of KS;analyze the role of the pathway in the growth of KS.Methods:(1)A unified format questionnaire was formulated,and 2 researchers were trained to investigate the subjects.Binary logistic regression was used to analyze the survey results.(2)The exp-ression of CD31,CD34 and D2-40 in SLK cells in vitro and 40 paraffin-embedded tissues of KS was detected by immunohistochemistry(The patients including 29 Uygur,three Han,seven Hakesa,and one Siberian Chinese;Thirty-three males and 7 females;Ten cases were HIV seropositive and 35 cases were human herpesvirus 8(HHV8)seropositive).A systematic literature retrieval in Cochrane Library,Pubmed,Embase,CNKI,VIP,Wanfang Data,CBM and Google Books was conducted and qualitative system evaluation was adopted.(3)The mimic and inhibitor of miR-126 were transfected into SLK cells and PTEN?AKT1 expression was assayed in SLK cells by real-time quantitative PCR and western blotting.PTEN,AKT1,phosphorylated(P)-PTEN,and phosphorylated(P)-AKT expression in KS and normal skin were assayed by immunohistochemistry.(4)The above methods were used to detect the expression of PDK1 and AKT2.Results:(1)Univariate analysis showed that significant variables included gender,age,nationality,BMI,education,marital status,smoking,alcohol consumption,frequency of food sacs,frequency of bathing,and other diseases.In multivariable models,Gender(OR = 0.010,95%Cl:0.002-0.068,P<0.001),frequency of consumption of sputum(OR=0.064,95%Cl:0.009-0.475,P=0.007)were negative correlation factor for KS incidence;Bathing frequency(OR=3.483;95%CI:1.285-9.459;P = 0.014),smoking(OR=33373.590;95%CI:8.152-1396158;P=0.008)were positively correlated factors in the pathogenesis of KS.The results of the interaction showed that the frequency of edible meal and ethnic interacted in the onset of Kaposi's sarcoma(OR=2.565,95%CI:1-6.580,P=0.050);ethnic and smoking history had an interaction in the onset of Kaposi's sarcoma(OR=0.039,95%CI:0.002-0.601,P=0.020);ethnic and drinking history had an interaction in the onset of Kaposi's sarcoma(OR-5.740,95%CI:1.917-17.189,P=0.002).(2)CD31and CD34 were expressed but D2-40 was not in SLK cells in vitro;In paraffin-embedded block of KS,the expression of CD31 and CD34 was significantly higher in HHV8 seropositive group than in HHV8 seronegative group;The expression of D2-40 was significantly higher in nodule group than in plaques/patch group and significantly higher in>lyear group than in?lyear group.The literature review retrieved 312 references and 10 publications were included.There were three controversial points about the origin of KS:human herpesvirus 8 infection and cell transformation,Lymphatic origin,Vascular origin.(3)AKT1 expression was downregulated in SLK cells that overexpressed miR-126,while there was no significant difference in PTEN expression between SLK cells overexpressing miR-126 and those in which its expression was knocked down.PTEN and AKT1 were expressed in KS and normal skin but P-AKT was not.Interestingly,P-PTEN was not expressed in normal skin but it was expressed in 90%of KS biopsies(P<0.05).P-PTEN expression was also significantly higher in visceral than in cutaneous KS(P=0.01)and was higher in indoor than in outdoor workers(P=0.018).(4)The expression of PDK1 was downregulated in SLK cells that overexpressed miR-126.PDK1 expression was higher in KS than in normal skin by immunohistochemistry(p<0.001)and in KS patients with a duration of less than 1 years it was significantly higher than that in patients with more than 1 years of disease(p=0.013).The expression of AKT2 was not observed in SLK cells in vitro,in KS and normal skin tissues.Conclusions:(1)Gender and frequency of eating cockroaches is a negative correlation factor for the onset of KS;Bathing frequency and smoking are positively correlated factor for the onset of KS;The frequency of consumption of cockroaches,smoking and drinking have an interaction with the nationality in KS.(2)Combined with the experiment and literature research of this subject,we deduce that spindle cells of KS were derived from HHV8 infected progenitor cells,which subsequently transformed into cells with mature vascular endothelial cell markers;In the progression of KS,cells with lymphatic endothelial characteristic were involved.We support the point of vascular origin of the KS.(3)In vitro,miR-126 negatively regulated AKT1 expression but no regulation of PTEN expression was evident.Results indicated that in KS,PTEN is activated and may therefore be a potential therapeutic target for KS.In addition,these results also indicate that sunlight may not be the cause of KS.(4)miR-126 negatively regulates the expression of PDK1 in SLK cells in vitro.The expression of PDK1 in KS mainly occurs in the early stage of the disease.In theory,PDK1 can be targets for the treatment of KS.