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Network analyses identify liver-specific targets for treating liver diseases

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Network analyses identify liver-specific targets for treating liver diseases. / Lee, Sunjae; Zhang, Cheng; Liu, Zhengtao; Klevstig, Martina; Mukhopadhyay, Bani; Bergentall, Mattias; Cinar, Resat; Stahlman, Marcus; Sikanic, Natasha; Park, Joshua K.; Deshmukh, Sumit; Harzandi, Azadeh M.; Kuijpers, Tim; Grotli, Morten; Elsasser, Simon J.; Piening, Brian D.; Snyder, Michael; Smith, Ulf; Nielsen, Jens; Backhed, Fredrik; Kunos, George; Uhlen, Mathias; Boren, Jan; Mardinoglu, Adil.

In: Molecular Systems Biology, Vol. 13, No. 8, 08.2017.

Research output: Contribution to journalArticle

Harvard

Lee, S, Zhang, C, Liu, Z, Klevstig, M, Mukhopadhyay, B, Bergentall, M, Cinar, R, Stahlman, M, Sikanic, N, Park, JK, Deshmukh, S, Harzandi, AM, Kuijpers, T, Grotli, M, Elsasser, SJ, Piening, BD, Snyder, M, Smith, U, Nielsen, J, Backhed, F, Kunos, G, Uhlen, M, Boren, J & Mardinoglu, A 2017, 'Network analyses identify liver-specific targets for treating liver diseases', Molecular Systems Biology, vol. 13, no. 8. https://doi.org/10.15252/msb.20177703

APA

Lee, S., Zhang, C., Liu, Z., Klevstig, M., Mukhopadhyay, B., Bergentall, M., ... Mardinoglu, A. (2017). Network analyses identify liver-specific targets for treating liver diseases. Molecular Systems Biology, 13(8). https://doi.org/10.15252/msb.20177703

Vancouver

Lee S, Zhang C, Liu Z, Klevstig M, Mukhopadhyay B, Bergentall M et al. Network analyses identify liver-specific targets for treating liver diseases. Molecular Systems Biology. 2017 Aug;13(8). https://doi.org/10.15252/msb.20177703

Author

Lee, Sunjae ; Zhang, Cheng ; Liu, Zhengtao ; Klevstig, Martina ; Mukhopadhyay, Bani ; Bergentall, Mattias ; Cinar, Resat ; Stahlman, Marcus ; Sikanic, Natasha ; Park, Joshua K. ; Deshmukh, Sumit ; Harzandi, Azadeh M. ; Kuijpers, Tim ; Grotli, Morten ; Elsasser, Simon J. ; Piening, Brian D. ; Snyder, Michael ; Smith, Ulf ; Nielsen, Jens ; Backhed, Fredrik ; Kunos, George ; Uhlen, Mathias ; Boren, Jan ; Mardinoglu, Adil. / Network analyses identify liver-specific targets for treating liver diseases. In: Molecular Systems Biology. 2017 ; Vol. 13, No. 8.

Bibtex Download

@article{7f6f2e84582d40a690ea052c235d4003,
title = "Network analyses identify liver-specific targets for treating liver diseases",
abstract = "We performed integrative network analyses to identify targets that can be used for effectively treating liver diseases with minimal side effects. We first generated co‐expression networks (CNs) for 46 human tissues and liver cancer to explore the functional relationships between genes and examined the overlap between functional and physical interactions. Since increased de novo lipogenesis is a characteristic of nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC), we investigated the liver‐specific genes co‐expressed with fatty acid synthase (FASN). CN analyses predicted that inhibition of these liver‐specific genes decreases FASN expression. Experiments in human cancer cell lines, mouse liver samples, and primary human hepatocytes validated our predictions by demonstrating functional relationships between these liver genes, and showing that their inhibition decreases cell growth and liver fat content. In conclusion, we identified liver‐specific genes linked to NAFLD pathogenesis, such as pyruvate kinase liver and red blood cell (PKLR), or to HCC pathogenesis, such as PKLR, patatin‐like phospholipase domain containing 3 (PNPLA3), and proprotein convertase subtilisin/kexin type 9 (PCSK9), all of which are potential targets for drug development.",
keywords = "co-expression, co-regulation, HCC, metabolism, NAFLD",
author = "Sunjae Lee and Cheng Zhang and Zhengtao Liu and Martina Klevstig and Bani Mukhopadhyay and Mattias Bergentall and Resat Cinar and Marcus Stahlman and Natasha Sikanic and Park, {Joshua K.} and Sumit Deshmukh and Harzandi, {Azadeh M.} and Tim Kuijpers and Morten Grotli and Elsasser, {Simon J.} and Piening, {Brian D.} and Michael Snyder and Ulf Smith and Jens Nielsen and Fredrik Backhed and George Kunos and Mathias Uhlen and Jan Boren and Adil Mardinoglu",
year = "2017",
month = "8",
doi = "10.15252/msb.20177703",
language = "English",
volume = "13",
journal = "Molecular Systems Biology",
issn = "1744-4292",
publisher = "Wiley-Blackwell",
number = "8",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Network analyses identify liver-specific targets for treating liver diseases

AU - Lee, Sunjae

AU - Zhang, Cheng

AU - Liu, Zhengtao

AU - Klevstig, Martina

AU - Mukhopadhyay, Bani

AU - Bergentall, Mattias

AU - Cinar, Resat

AU - Stahlman, Marcus

AU - Sikanic, Natasha

AU - Park, Joshua K.

AU - Deshmukh, Sumit

AU - Harzandi, Azadeh M.

AU - Kuijpers, Tim

AU - Grotli, Morten

AU - Elsasser, Simon J.

AU - Piening, Brian D.

AU - Snyder, Michael

AU - Smith, Ulf

AU - Nielsen, Jens

AU - Backhed, Fredrik

AU - Kunos, George

AU - Uhlen, Mathias

AU - Boren, Jan

AU - Mardinoglu, Adil

PY - 2017/8

Y1 - 2017/8

N2 - We performed integrative network analyses to identify targets that can be used for effectively treating liver diseases with minimal side effects. We first generated co‐expression networks (CNs) for 46 human tissues and liver cancer to explore the functional relationships between genes and examined the overlap between functional and physical interactions. Since increased de novo lipogenesis is a characteristic of nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC), we investigated the liver‐specific genes co‐expressed with fatty acid synthase (FASN). CN analyses predicted that inhibition of these liver‐specific genes decreases FASN expression. Experiments in human cancer cell lines, mouse liver samples, and primary human hepatocytes validated our predictions by demonstrating functional relationships between these liver genes, and showing that their inhibition decreases cell growth and liver fat content. In conclusion, we identified liver‐specific genes linked to NAFLD pathogenesis, such as pyruvate kinase liver and red blood cell (PKLR), or to HCC pathogenesis, such as PKLR, patatin‐like phospholipase domain containing 3 (PNPLA3), and proprotein convertase subtilisin/kexin type 9 (PCSK9), all of which are potential targets for drug development.

AB - We performed integrative network analyses to identify targets that can be used for effectively treating liver diseases with minimal side effects. We first generated co‐expression networks (CNs) for 46 human tissues and liver cancer to explore the functional relationships between genes and examined the overlap between functional and physical interactions. Since increased de novo lipogenesis is a characteristic of nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC), we investigated the liver‐specific genes co‐expressed with fatty acid synthase (FASN). CN analyses predicted that inhibition of these liver‐specific genes decreases FASN expression. Experiments in human cancer cell lines, mouse liver samples, and primary human hepatocytes validated our predictions by demonstrating functional relationships between these liver genes, and showing that their inhibition decreases cell growth and liver fat content. In conclusion, we identified liver‐specific genes linked to NAFLD pathogenesis, such as pyruvate kinase liver and red blood cell (PKLR), or to HCC pathogenesis, such as PKLR, patatin‐like phospholipase domain containing 3 (PNPLA3), and proprotein convertase subtilisin/kexin type 9 (PCSK9), all of which are potential targets for drug development.

KW - co-expression

KW - co-regulation

KW - HCC

KW - metabolism

KW - NAFLD

U2 - 10.15252/msb.20177703

DO - 10.15252/msb.20177703

M3 - Article

VL - 13

JO - Molecular Systems Biology

JF - Molecular Systems Biology

SN - 1744-4292

IS - 8

ER -

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