TFRC通过JAK-STAT信号通路影响宫颈鳞状细胞癌的增殖、迁移和侵袭

TFRC affects the proliferation,metastasis and1 invasion of cervical squamouss cell carcinomat ht rough JAK-STAT signaling pathway

目的探讨转铁蛋白受体(transferrin receptor,TFRC)通过JAK-STAT通路对宫颈鳞状细胞癌的增殖、迁移和侵袭的影响。方法收集2020年8月至2021年12月于青岛市市立医院就诊的30例宫颈鳞状细胞癌患者的组织标本和20例正常宫颈者的组织进行免疫组织化学检测TFRC的表达情况;用慢病毒构建TFRC敲低的Hela和Siha细胞稳转株;用CCK8、Transwell迁移和侵袭实验方法检测各组细胞的增殖、迁移和侵袭能力;用蛋白印迹分析法等方法检测TFRC表达量及JAK-STAT通路相关蛋白表达情况;为进一步明确TFRC是否通过JAK-STAT通路发挥作用,于Hela细胞的TFRC敲低组中加入JAK通路激动剂(Coumermycin A1)后,行功能回复实验,验证其相关性。结果通过分析免疫组化结果发现TFRC在宫颈鳞状细胞癌组织呈高表达(P<0.05);细胞实验证明敲低TFRC后细胞增殖、迁移和侵袭能力均下降(P<0.05),抑制宫颈鳞状细胞癌的进展,JAK-STAT通路相关蛋白表达水平下降(P<0.05);而加入Coumermycin A1后JAK-STAT通路相关蛋白表达水平升高,且可逆转敲低TFRC后所产生的抑制作用(P<0.05)。结论TFRC在宫颈鳞状细胞癌中呈高表达,可能通过影响JAK-STAT通路促进宫颈鳞状细胞癌的增殖、迁移和侵袭。

Objective To investigate the effect of transferrin receptor(TFRC)on the proliferation,migration and invasion of cervical squamous cell carcinoma by affecting the JAK-STAT pathway.Methods Tissue samples from 30 patients with cervical squamous cell carcinoma and 20 normal cervical tissues treated at Qingdao Municipal Hospital from August 2020 to December 2021 were collected for immunohistochemical detection of TFRC expression.Lentivirus was used to construct Hela and Siha cell stable strains with low TFRC expression.CCK8,Transwell migration and invasion assay were used to detect cell proliferation,migration and invasion.Western blot was used to measure the levels of TFRC and JAK-STAT pathway related proteins.In order to further elucidate if TFRC promotes cancer development through the JAK-STAT pathway,added a JAK pathway agonist(Coumermycin AI)to the TFRC knockdown group of Hela cells,carried out a functional recovery assay to confirm the correlation.Results By analyzing the immunohistochemical results,we found that TFRC was highly expressed in cervical squamous cell carcinoma(P<0.05).Cell experiments showed that the proliferation,migration and invasion of cells were decreased after TFRC knockdown(P<O.05),which inhibited the progression of cervical squamous cell carcinoma.In addition,the expression level of JAK-STAT pathway related proteins was also decreased(P<0.05).After addition of Coumermycin A1,the expression level of JAK-STAT pathway related protein was increased.The inhibitory effect of TFRC knockdown was reversed(P<0.05).Conclusion TFRC is highly expressed in cervical squamous cellcarcinoma.Itcan promote the proliferation,migration and invasion of cervical squamous cellcarcinoma by affecting the JAK-STAT pathway.