食管鳞癌中SERPINB5表达降低的作用机制及其临床意义

doi:10.3969/j.issn.1004-616x.2021.02.004

Abstract

Abstract: OBJCTIVE: To investigate expression and role of SERPINB5 in esophageal squamous cell carcinomas (ESCC). METHODS: Expression of SERPINB5 mRNA in ESCC tissues was analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. ESCC specimens and their matched morphologically normal operative margins were used to detect SERPINB5 protein expressions using the Western blot technique. Relationship between SERPINB5 expressions and the clinicopathological parameters of ESCC patients were analyzed. Furthermore,ESCC cells were transfected with an SERPINB5 over-expression vector,the empty vector or without any vectors (parental). These cells were used to detect proliferation and clony formation to determine the roles of SERPINB5. Effects of SERPINB5 on tumorigenesis were detected using the nude mouse xenograft model in vivo. Western blot was used to analyze changes in downstream pathways from over-expression of SERPINB5. Finally,potentials of SERPINB5 in treatment of ESCC through targeted inhibition were investigated. RESULTS: Expression levels of both the SERPINB5 mRNA and protein were down regulated in ESCC compared with the normal tissues (P<0.01). In addition,lower SERPINB5 mRNA levels were correlated with lower degrees of tumor differentiation (P=0.004) but higher clinical stages (P=0.037). From our in vitro and in vivo studies,our results show that over-expression of SERPINB5 significantly inhibited the proliferation and colony formation of ESCC cells,as well as the growth of tumor xenografts (P<0.05). At the molecular level,over-expression of SERPINB5 decreased the phosphorylation levels of AKT and mTOR. Data from targeted inhibition experiments show that the over expression of SERPINB5 significantly increased the sensitivities of ESCC cells to Alisertib (Aurora A inhibitor) or Everolimus (mTOR inhibitor) (P<0.01). CONCLUSION: SERPINB5 acted as a tumor suppressor in ESCC. Elevating the expression of SERPINB5 in tumor cells might be a potential strategy for the treatment of ESCC.

Key words: SERPINB5, esophageal squamous cell carcinoma, cell proliferation, tumor suppressor, drug sensitivity

CLC Number:

R735.1

ZHANG Na, FAN Zhilu, YANG Liyan, CHANG Chen, CAI Yan, HAO Jiajie, WANG Mingrong. Clinical significance of decreased SERPINB5 expression in esophageal squamous cell carcinomas[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(2): 101-109.

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Clinical significance of decreased SERPINB5 expression in esophageal squamous cell carcinomas

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