The globular heads of the C1q receptor regulate apoptosis in human cervical squamous carcinoma cells via a p53-dependent pathwayReportar como inadecuado




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Journal of Translational Medicine

, 10:255

Cancer microenvironment

Abstract

BackgroundThe globular heads of the human C1q receptor gC1qR localize predominantly to the mitochondrial matrix. gC1qR mediates many biological responses, including growth perturbation, morphological abnormalities and the initiation of apoptosis. The purpose of this study was to investigate the relationship between mitochondrial dysfunction, p53 status and gC1qR expression and the regulation of apoptosis in human cervical squamous carcinoma cells C33a and SiHa.

MethodsHere, gC1qR expression was examined in human cervical tissues using real-time PCR and Western blot analysis. Apoptotic death of C33a and SiHa cells was assessed by flow cytometric analysis that detected the subG1 population. Mitochondrial function was assessed via ROS generation, the content of cytosolic Ca, and the change in mitochondrial membrane potential Δψm. The viability and migration of C33a and SiHa cells were detected via the water-soluble tetrazolium salt WST-1 assay and the transwell assay, respectively.

ResultsgC1qR expression was decreased in cervical squamous cell carcinoma tissues compared with normal tissues. C33a and SiHa cells transfected with a vector encoding gC1qR displayed mitochondrial dysfunction and apoptosis, which was abrogated by the addition of a mutant form of p53 or p53 small interference RNA siRNA. Furthermore, upon overexpression of gC1qR, cell viability and migration were significantly enhanced, and the apoptosis of C33a and SiHa cells were decreased when cells were treated with mutant p53 or p53 siRNA.

ConclusionsThese data support a mechanism whereby gC1qR induces apoptosis through the mitochondrial and p53-dependent pathways in cervical squamous cell carcinoma.

KeywordsGlobular heads of the human C1q receptor gC1qR Apoptosis Mitochondria p53 Human cervical squamous carcinoma cells AbbreviationsgC1qRGlobular heads of C1q receptor

ROSReactive oxygen species

ΔψmMitochondrial membrane potential

siRNASmall interference RNA

SOCSSuppressor of cytokine signaling

PIPropidium iodide

cDNAComplementary DNA

WST-1Water-soluble tetrazolium salt

SDStandard deviation

real-time PCRReal-time quantitative polymerase chain reaction

wtWild-type

mtMutant

H2DCFDA2-, 7-dichlorodihydrofluorescein diacetate.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-10-255 contains supplementary material, which is available to authorized users.

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Autor: Zheng-lin Chen - Ping-qing Gu - Kangsheng Liu - Ya-juan Su - Ling-juan Gao

Fuente: https://link.springer.com/







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