Transcriptomic analysis of pancreatic cancer cells in response to metformin and aspirin: An implication of synergy

Wen Yue; Tao Wang; Emmanuel Zachariah; Yong Lin; Chung S. Yang; Qing Xu; Robert S. DiPaola; Xiang Lin Tan

doi:10.1038/srep13390

Transcriptomic analysis of pancreatic cancer cells in response to metformin and aspirin: An implication of synergy

Wen Yue
, Tao Wang
, Emmanuel Zachariah
, Yong Lin
, Chung S. Yang
, Qing Xu
, Robert S. DiPaola
, Xiang Lin Tan

Producción científica: Article › revisión exhaustiva

37 Citas (Scopus)

Resumen

Metformin and aspirin have been studied extensively as cancer preventative and therapeutic agents. However, the underlying molecular mechanisms for the inhibitory effects of pancreatic cancer development remain undefined. To gain further insight into their biological function in pancreatic cancer, we conducted a transcriptomic analysis using RNA sequencing to assess the differential gene expression induced by metformin (5 mM) and aspirin (2 mM), alone or in combination, after treatment of PANC-1 cells for 48 hours. Compared to an untreated control, metformin down-regulated 58 genes and up-regulated 91 genes, aspirin down-regulated 12 genes only, while metformin plus aspirin down-regulated 656 genes and up-regulated 449 genes (fold-change > 2, P < 10^-5). Of the top 10 genes (fold-change > 10, P < 10^-10) regulated by metformin plus aspirin, PCDH18, CCL2, RASL11A, FAM111B and BMP5 were down-regulated ≥20-fold, while NGFR, NPTX1, C7orf57, MRPL23AS1 and UNC5B were up-regulated ≥10-fold. Ingenuity Pathway Analysis (IPA) revealed that the pathways, "cholesterol biosynthesis", "cell cycle: G1/S checkpoint regulation", and "axonal guidance signaling" were the most statistically significant pathways modulated by metformin plus aspirin. Although the results need further functional validation, these data provide the first evidence for the synergistic action between metformin and aspirin in modulating the transcriptional profile of pancreatic cancer cells.

Idioma original	English
Número de artículo	13390
Publicación	Scientific Reports
Volumen	5
DOI	https://doi.org/10.1038/srep13390
Estado	Published - ago 21 2015

Nota bibliográfica

Funding Information:
This work was supported by Rutgers Robert Wood Johnson Foundation research funds and the Functional Genomics Core Shared Resource of the Rutgers Cancer Institute of New Jersey (P30CA072720) and a grant (Grant No. 81470132) from the National Natural Science Foundation of China. We also thank RUCDR for the RNA sequencing.

Financiación

This work was supported by Rutgers Robert Wood Johnson Foundation research funds and the Functional Genomics Core Shared Resource of the Rutgers Cancer Institute of New Jersey (P30CA072720) and a grant (Grant No. 81470132) from the National Natural Science Foundation of China. We also thank RUCDR for the RNA sequencing.

Financiadores	Número del financiador
National Childhood Cancer Registry – National Cancer Institute	P30CA072720
National Childhood Cancer Registry – National Cancer Institute
Robert Wood Johnson Foundation
Rutgers Cancer Institute of New Jersey and Rutgers University	81470132
Rutgers Cancer Institute of New Jersey and Rutgers University
National Natural Science Foundation of China (NSFC)

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title = "Transcriptomic analysis of pancreatic cancer cells in response to metformin and aspirin: An implication of synergy",

abstract = "Metformin and aspirin have been studied extensively as cancer preventative and therapeutic agents. However, the underlying molecular mechanisms for the inhibitory effects of pancreatic cancer development remain undefined. To gain further insight into their biological function in pancreatic cancer, we conducted a transcriptomic analysis using RNA sequencing to assess the differential gene expression induced by metformin (5 mM) and aspirin (2 mM), alone or in combination, after treatment of PANC-1 cells for 48 hours. Compared to an untreated control, metformin down-regulated 58 genes and up-regulated 91 genes, aspirin down-regulated 12 genes only, while metformin plus aspirin down-regulated 656 genes and up-regulated 449 genes (fold-change > 2, P < 10-5). Of the top 10 genes (fold-change > 10, P < 10-10) regulated by metformin plus aspirin, PCDH18, CCL2, RASL11A, FAM111B and BMP5 were down-regulated ≥20-fold, while NGFR, NPTX1, C7orf57, MRPL23AS1 and UNC5B were up-regulated ≥10-fold. Ingenuity Pathway Analysis (IPA) revealed that the pathways, {"}cholesterol biosynthesis{"}, {"}cell cycle: G1/S checkpoint regulation{"}, and {"}axonal guidance signaling{"} were the most statistically significant pathways modulated by metformin plus aspirin. Although the results need further functional validation, these data provide the first evidence for the synergistic action between metformin and aspirin in modulating the transcriptional profile of pancreatic cancer cells.",

author = "Wen Yue and Tao Wang and Emmanuel Zachariah and Yong Lin and Yang, \{Chung S.\} and Qing Xu and DiPaola, \{Robert S.\} and Tan, \{Xiang Lin\}",

note = "Funding Information: This work was supported by Rutgers Robert Wood Johnson Foundation research funds and the Functional Genomics Core Shared Resource of the Rutgers Cancer Institute of New Jersey (P30CA072720) and a grant (Grant No. 81470132) from the National Natural Science Foundation of China. We also thank RUCDR for the RNA sequencing.",

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AU - Xu, Qing

AU - DiPaola, Robert S.

AU - Tan, Xiang Lin

N1 - Funding Information: This work was supported by Rutgers Robert Wood Johnson Foundation research funds and the Functional Genomics Core Shared Resource of the Rutgers Cancer Institute of New Jersey (P30CA072720) and a grant (Grant No. 81470132) from the National Natural Science Foundation of China. We also thank RUCDR for the RNA sequencing.

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Transcriptomic analysis of pancreatic cancer cells in response to metformin and aspirin: An implication of synergy

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