Genome editing of LKB1 (STK11) mutation in A549 lung cancer cells using CRISPR/Cas9 system

Mutations and deletions of the tumor suppressor LKB1 (STK11) are common in several malignancies, especially in non-small lung cancer cells (NSCLC). In that cell type, LKB1 inactivation coexists with mutations at other important cancer genes, including KRAS and TP53. The mutant LKB1 indirectly increa...

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Main Authors: Morelli, Ana Paula, Simabuco, Fernando Moreira, Pavan, Isadora Carolina B., Tavares, Mariana Rosolen, Salvino, Luiz Guilherme, Pereira, Nathalie F. P., Silva, Fernando Riback, Junior, Tharcisio Citrangulo Tortelli, Chammas, Roger
Format: Online
Language:English
Published: Universidade Estadual de Campinas 2018
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Online Access:https://econtents.sbu.unicamp.br/eventos/index.php/pibic/article/view/138
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author Morelli, Ana Paula
Simabuco, Fernando Moreira
Pavan, Isadora Carolina B.
Tavares, Mariana Rosolen
Salvino, Luiz Guilherme
Pereira, Nathalie F. P.
Silva, Fernando Riback
Junior, Tharcisio Citrangulo Tortelli
Chammas, Roger
author_facet Morelli, Ana Paula
Simabuco, Fernando Moreira
Pavan, Isadora Carolina B.
Tavares, Mariana Rosolen
Salvino, Luiz Guilherme
Pereira, Nathalie F. P.
Silva, Fernando Riback
Junior, Tharcisio Citrangulo Tortelli
Chammas, Roger
author_sort Morelli, Ana Paula
collection Portal de Eventos Científicos da UNICAMP
container_reference Revista dos Trabalhos de Iniciação Científica da UNICAMP; n. 26 (2018): Congresso de Iniciação Científica Unicamp
description Mutations and deletions of the tumor suppressor LKB1 (STK11) are common in several malignancies, especially in non-small lung cancer cells (NSCLC). In that cell type, LKB1 inactivation coexists with mutations at other important cancer genes, including KRAS and TP53. The mutant LKB1 indirectly increases transcription of genes involved in metastasis, including COX-2. LKB1 directly activates AMPK decreasing mTOR activity and plays roles in several other processes such as cell metabolism, cell polarity, apoptosis and DNA damage via p53 interaction. Metformin, an antidiabetic drug, have shown antitumor effects, sensitizes cells in coadjuvant cisplatin treatment and acts in AMPK independent and dependent mechanisms. Thus, we propose the application of CRISPR/Cas9 system as genome editing tool to correct the LKB1 nonsense mutation and restore protein expression, providing new insights regarding cisplatin resistance, survival and metformin response in A549 lung cancer cells.
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spelling ojs-article-1382025-09-26T14:32:30Z Genome editing of LKB1 (STK11) mutation in A549 lung cancer cells using CRISPR/Cas9 system Morelli, Ana Paula Simabuco, Fernando Moreira Pavan, Isadora Carolina B. Tavares, Mariana Rosolen Salvino, Luiz Guilherme Pereira, Nathalie F. P. Silva, Fernando Riback Junior, Tharcisio Citrangulo Tortelli Chammas, Roger CRESPR/Cas9 LKB1 Lung Cancer. Mutations and deletions of the tumor suppressor LKB1 (STK11) are common in several malignancies, especially in non-small lung cancer cells (NSCLC). In that cell type, LKB1 inactivation coexists with mutations at other important cancer genes, including KRAS and TP53. The mutant LKB1 indirectly increases transcription of genes involved in metastasis, including COX-2. LKB1 directly activates AMPK decreasing mTOR activity and plays roles in several other processes such as cell metabolism, cell polarity, apoptosis and DNA damage via p53 interaction. Metformin, an antidiabetic drug, have shown antitumor effects, sensitizes cells in coadjuvant cisplatin treatment and acts in AMPK independent and dependent mechanisms. Thus, we propose the application of CRISPR/Cas9 system as genome editing tool to correct the LKB1 nonsense mutation and restore protein expression, providing new insights regarding cisplatin resistance, survival and metformin response in A549 lung cancer cells. Universidade Estadual de Campinas 2018-12-04 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Artigo de convidado application/pdf https://econtents.sbu.unicamp.br/eventos/index.php/pibic/article/view/138 10.20396/revpibic262018138 Revista dos Trabalhos de Iniciação Científica da UNICAMP; n. 26 (2018): Congresso de Iniciação Científica Unicamp 2596-1969 eng https://econtents.sbu.unicamp.br/eventos/index.php/pibic/article/view/138/117 Copyright (c) 2018 Ana Paula Morelli, Fernando Moreira Simabuco http://creativecommons.org/licenses/by/4.0
spellingShingle Morelli, Ana Paula
Simabuco, Fernando Moreira
Pavan, Isadora Carolina B.
Tavares, Mariana Rosolen
Salvino, Luiz Guilherme
Pereira, Nathalie F. P.
Silva, Fernando Riback
Junior, Tharcisio Citrangulo Tortelli
Chammas, Roger
CRESPR/Cas9
LKB1
Lung Cancer.
Genome editing of LKB1 (STK11) mutation in A549 lung cancer cells using CRISPR/Cas9 system
title Genome editing of LKB1 (STK11) mutation in A549 lung cancer cells using CRISPR/Cas9 system
title_full Genome editing of LKB1 (STK11) mutation in A549 lung cancer cells using CRISPR/Cas9 system
title_fullStr Genome editing of LKB1 (STK11) mutation in A549 lung cancer cells using CRISPR/Cas9 system
title_full_unstemmed Genome editing of LKB1 (STK11) mutation in A549 lung cancer cells using CRISPR/Cas9 system
title_short Genome editing of LKB1 (STK11) mutation in A549 lung cancer cells using CRISPR/Cas9 system
title_sort genome editing of lkb1 (stk11) mutation in a549 lung cancer cells using crispr/cas9 system
topic CRESPR/Cas9
LKB1
Lung Cancer.
url https://econtents.sbu.unicamp.br/eventos/index.php/pibic/article/view/138
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