Identification of AGR2 Gene-Specific Expression Patterns Associated with Epithelial-Mesenchymal Transition

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F22%3A00079069" target="_blank" >RIV/00209805:_____/22:00079069 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14310/22:00126708

Výsledek na webu

<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9504245/" target="_blank" >https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9504245/</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/ijms231810845" target="_blank" >10.3390/ijms231810845</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Identification of AGR2 Gene-Specific Expression Patterns Associated with Epithelial-Mesenchymal Transition

Popis výsledku v původním jazyce

The TGF-beta signaling pathway is involved in numerous cellular processes, and its deregulation may result in cancer development. One of the key processes in tumor progression and metastasis is epithelial to mesenchymal transition (EMT), in which TGF-beta signaling plays important roles. Recently, AGR2 was identified as a crucial component of the cellular machinery responsible for maintaining the epithelial phenotype, thereby interfering with the induction of mesenchymal phenotype cells by TGF-beta effects in cancer. Here, we performed transcriptomic profiling of A549 lung cancer cells with CRISPR-Cas9 mediated AGR2 knockout with and without TGF-beta treatment. We identified significant changes in transcripts associated with focal adhesion and eicosanoid production, in particular arachidonic acid metabolism. Changes in transcripts associated with the focal adhesion pathway were validated by RT-qPCR of COL4A1, COL4A2, FLNA, VAV3, VEGFA, and VINC mRNAs. In addition, immunofluorescence showed the formation of stress fibers and vinculin foci in cells without AGR2 and in response to TGF-13 treatment, with synergistic effects observed. These findings imply that both AGR2 downregulation and TGF-beta have a role in focal adhesion formation and cancer cell migration and invasion. Transcripts associated with arachidonic acid metabolism were downregulated after both AGR2 knockout and TGF-beta treatment and were validated by RT-qPCR of GPX2, PTGS2, and PLA2G4A. Since PGE(2) is a product of arachidonic acid metabolism, its lowered concentration in media from AGR2-knockout cells was confirmed by ELISA. Together, our results demonstrate that AGR2 downregulation and TGF-beta have an essential role in focal adhesion formation; moreover, we have identified AGR2 as an important component of the arachidonic acid metabolic pathway.

Název v anglickém jazyce

Identification of AGR2 Gene-Specific Expression Patterns Associated with Epithelial-Mesenchymal Transition

Popis výsledku anglicky

The TGF-beta signaling pathway is involved in numerous cellular processes, and its deregulation may result in cancer development. One of the key processes in tumor progression and metastasis is epithelial to mesenchymal transition (EMT), in which TGF-beta signaling plays important roles. Recently, AGR2 was identified as a crucial component of the cellular machinery responsible for maintaining the epithelial phenotype, thereby interfering with the induction of mesenchymal phenotype cells by TGF-beta effects in cancer. Here, we performed transcriptomic profiling of A549 lung cancer cells with CRISPR-Cas9 mediated AGR2 knockout with and without TGF-beta treatment. We identified significant changes in transcripts associated with focal adhesion and eicosanoid production, in particular arachidonic acid metabolism. Changes in transcripts associated with the focal adhesion pathway were validated by RT-qPCR of COL4A1, COL4A2, FLNA, VAV3, VEGFA, and VINC mRNAs. In addition, immunofluorescence showed the formation of stress fibers and vinculin foci in cells without AGR2 and in response to TGF-13 treatment, with synergistic effects observed. These findings imply that both AGR2 downregulation and TGF-beta have a role in focal adhesion formation and cancer cell migration and invasion. Transcripts associated with arachidonic acid metabolism were downregulated after both AGR2 knockout and TGF-beta treatment and were validated by RT-qPCR of GPX2, PTGS2, and PLA2G4A. Since PGE(2) is a product of arachidonic acid metabolism, its lowered concentration in media from AGR2-knockout cells was confirmed by ELISA. Together, our results demonstrate that AGR2 downregulation and TGF-beta have an essential role in focal adhesion formation; moreover, we have identified AGR2 as an important component of the arachidonic acid metabolic pathway.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/LX22NPO5102" target="_blank" >LX22NPO5102: Národní ústav pro výzkum rakoviny</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2022

Kód důvěrnosti údajů

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

Název periodika

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

ISSN

1422-0067

e-ISSN

1422-0067

Svazek periodika

23

Číslo periodika v rámci svazku

18

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

19

Strana od-do

10845

Kód UT WoS článku

000858720400001

EID výsledku v databázi Scopus

2-s2.0-85138382711