Systems-level effects of ectopic galectin-7 reconstitution in cervical cancer and its microenvironment

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F16%3A43875624" target="_blank" >RIV/60162694:G44__/16:43875624 - isvavai.cz</a>

Výsledek na webu

<a href="https://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2700-8" target="_blank" >https://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2700-8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12885-016-2700-8" target="_blank" >10.1186/s12885-016-2700-8</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Systems-level effects of ectopic galectin-7 reconstitution in cervical cancer and its microenvironment

Popis výsledku v původním jazyce

Galectin-7 is negatively regulated in cervical cancer and appears to be a link between apoptotic response triggered by cancer and anti-tumoral activity of the immune system. Our understanding of how cervical cancer cells and their molecular networks adapt in response to the expression of Gal-7 remains limited. Meta-analysis of Gal-7 expression was conducted in three cervical cancer cohort studies and TCGA. In silico prediction and bisulfite sequencing were performed to inquire epigenetic alterations. To study the effect of Gal-7 on cervical cancer we ectopically re-expressed it in HeLa and SiHa cervical cancer cell lines and analyzed their transcriptome and SILAC-based proteome. We also examined the tumor and microenvironment host cell transcriptomes after xenotransplantation into immunocompromised mice. Gal-7 was constantly downregulated in our meta-analysis. Tumors with combined high Gal-7 and low galectin-1 expression presented significantly better prognoses. In silico and bisulfite sequencing assays showed de novo methylation in the Gal-7 promoter and first intron. Cells re-expressing Gal-7 showed a high apoptosis ratio and their xenografts displayed strong growth retardation. Multiple gene modules and transcriptional regulators were modulated in response to Gal-7 reconstitution, both in cervical cancer cells and their microenvironments. Most of these genes and modules were associated with tissue morphogenesis, metabolism, transport, chemokine activity and immune response. These functional modules could exert the same effects in vitro and in vivo, even despite different compositions between HeLa and SiHa samples. Gal-7 re-expression affects the regulation of molecular networks in cervical cancer that are involved in diverse cancer hallmarks such as metabolism, growth control, invasion and evasion of apoptosis. The effect of Gal-7 extends to the microenvironment, where networks involved in its configuration and in immune surveillance are particularly affected.

Název v anglickém jazyce

Systems-level effects of ectopic galectin-7 reconstitution in cervical cancer and its microenvironment

Popis výsledku anglicky

Galectin-7 is negatively regulated in cervical cancer and appears to be a link between apoptotic response triggered by cancer and anti-tumoral activity of the immune system. Our understanding of how cervical cancer cells and their molecular networks adapt in response to the expression of Gal-7 remains limited. Meta-analysis of Gal-7 expression was conducted in three cervical cancer cohort studies and TCGA. In silico prediction and bisulfite sequencing were performed to inquire epigenetic alterations. To study the effect of Gal-7 on cervical cancer we ectopically re-expressed it in HeLa and SiHa cervical cancer cell lines and analyzed their transcriptome and SILAC-based proteome. We also examined the tumor and microenvironment host cell transcriptomes after xenotransplantation into immunocompromised mice. Gal-7 was constantly downregulated in our meta-analysis. Tumors with combined high Gal-7 and low galectin-1 expression presented significantly better prognoses. In silico and bisulfite sequencing assays showed de novo methylation in the Gal-7 promoter and first intron. Cells re-expressing Gal-7 showed a high apoptosis ratio and their xenografts displayed strong growth retardation. Multiple gene modules and transcriptional regulators were modulated in response to Gal-7 reconstitution, both in cervical cancer cells and their microenvironments. Most of these genes and modules were associated with tissue morphogenesis, metabolism, transport, chemokine activity and immune response. These functional modules could exert the same effects in vitro and in vivo, even despite different compositions between HeLa and SiHa samples. Gal-7 re-expression affects the regulation of molecular networks in cervical cancer that are involved in diverse cancer hallmarks such as metabolism, growth control, invasion and evasion of apoptosis. The effect of Gal-7 extends to the microenvironment, where networks involved in its configuration and in immune surveillance are particularly affected.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FD - Onkologie a hematologie

OECD FORD obor

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Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

BMC Cancer

ISSN

1471-2407

e-ISSN

—

Svazek periodika

16

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

22

Strana od-do

"Art. No. 680"

Kód UT WoS článku

000384195800001

EID výsledku v databázi Scopus

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