microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer

MicroRNA is an endogenous, small RNA controlling multiple target genes and playing roles in various biological processes including tumorigenesis. Here, we addressed the function of miR-155 using LC-MS/MS-based metabolic profiling of miR-155 deficient breast cancer cells. Our results revealed the los...

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Published inOncogene Vol. 37; no. 22; pp. 2982 - 2991
Main Authors Kim, Sinae, Lee, Eunji, Jung, Jaeyun, Lee, Jong Won, Kim, Hee Jung, Kim, Jisun, Yoo, Hyun ju, Lee, Hee Jin, Chae, Sun Young, Jeon, Sang Min, Son, Byung Ho, Gong, Gyungyup, Sharan, Shyam K, Chang, Suhwan
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 01.05.2018
Nature Publishing Group
Subjects
13
3' Untranslated Regions
38/77
631/67/1347
631/67/2327
631/67/395
631/67/70
64
64/60
82/58
96
96/109
96/31
96/95
AKT protein
Animals
Apoptosis
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Care and treatment
Carrier proteins
Cell Biology
Cell Line, Tumor
Chromatography, Liquid
Development and progression
Female
Forkhead Box Protein O3 - genetics
FOXO3 protein
Gene Expression Regulation, Neoplastic
Genetic aspects
Genetic regulation
Glucose
Glucose - metabolism
Glycolysis
Health aspects
Human Genetics
Humans
Internal Medicine
Kinases
MCF-7 Cells
Medicine
Medicine & Public Health
Metabolism
Mice
MicroRNA
MicroRNAs
MicroRNAs - genetics
miRNA
Neoplasm Transplantation
Oncology
Phosphatidylinositol 3-Kinases - genetics
Proto-Oncogene Proteins c-myc - genetics
Signal Transduction
Tandem Mass Spectrometry
Tumorigenesis
South Korea
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Abstract MicroRNA is an endogenous, small RNA controlling multiple target genes and playing roles in various biological processes including tumorigenesis. Here, we addressed the function of miR-155 using LC-MS/MS-based metabolic profiling of miR-155 deficient breast cancer cells. Our results revealed the loss of miR-155 hampers glucose uptake and glycolysis, via the down-regulation of glucose transporters and metabolic enzymes including HK2, PKM2, and LDHA. We showed this is due to the down-regulation of cMYC, controlled through phosphoinositide-3-kinase regulatory subunit alpha (PIK3R1)-PDK1/AKT-FOXO3a pathway. UTR analysis of the PIK3R1 and FOXO3a indicated miR-155 directly represses these genes. A stable expression of miR-155 in patient-derived cells (PDCs) showed activated glucose metabolism whereas a stable inhibition of miR-155 reduced in vivo tumor growth with retarded glucose metabolism. Furthermore, analysis of 50 triple-negative breast cancer (TNBC) specimens and specific uptake value (SUV) of PET images revealed a positive correlation between miR-155 level and glucose usage in human breast tumors via PIK3R1-PDK/AKT-FOXO3a-cMYC axis. Collectively, these data demonstrate the miR-155 is a key regulator of glucose metabolism in breast cancer.
AbstractList MicroRNA is an endogenous, small RNA controlling multiple target genes and playing roles in various biological processes including tumorigenesis. Here, we addressed the function of miR-155 using LC-MS/MS-based metabolic profiling of miR-155 deficient breast cancer cells. Our results revealed the loss of miR-155 hampers glucose uptake and glycolysis, via the down-regulation of glucose transporters and metabolic enzymes including HK2, PKM2, and LDHA. We showed this is due to the down-regulation of cMYC, controlled through phosphoinositide-3-kinase regulatory subunit alpha (PIK3R1)-PDK1/AKT-FOXO3a pathway. UTR analysis of the PIK3R1 and FOXO3a indicated miR-155 directly represses these genes. A stable expression of miR-155 in patient-derived cells (PDCs) showed activated glucose metabolism whereas a stable inhibition of miR-155 reduced in vivo tumor growth with retarded glucose metabolism. Furthermore, analysis of 50 triple-negative breast cancer (TNBC) specimens and specific uptake value (SUV) of PET images revealed a positive correlation between miR-155 level and glucose usage in human breast tumors via PIK3R1-PDK/AKT-FOXO3a-cMYC axis. Collectively, these data demonstrate the miR-155 is a key regulator of glucose metabolism in breast cancer.
MicroRNA is an endogenous, small RNA controlling multiple target genes and playing roles in various biological processes including tumorigenesis. Here, we addressed the function of miR-155 using LC-MS/MS-based metabolic profiling of miR-155 deficient breast cancer cells. Our results revealed the loss of miR-155 hampers glucose uptake and glycolysis, via the down-regulation of glucose transporters and metabolic enzymes including HK2, PKM2, and LDHA. We showed this is due to the down-regulation of cMYC, controlled through phosphoinositide-3-kinase regulatory subunit alpha (PIK3R1)-PDK1/AKT-FOXO3a pathway. UTR analysis of the PIK3R1 and FOXO3a indicated miR-155 directly represses these genes. A stable expression of miR-155 in patient-derived cells (PDCs) showed activated glucose metabolism whereas a stable inhibition of miR-155 reduced in vivo tumor growth with retarded glucose metabolism. Furthermore, analysis of 50 triple-negative breast cancer (TNBC) specimens and specific uptake value (SUV) of PET images revealed a positive correlation between miR-155 level and glucose usage in human breast tumors via PIK3R1-PDK/AKT-FOXO3a-cMYC axis. Collectively, these data demonstrate the miR-155 is a key regulator of glucose metabolism in breast cancer.
AbstractMicroRNA is an endogenous, small RNA controlling multiple target genes and playing roles in various biological processes including tumorigenesis. Here, we addressed the function of miR-155 using LC-MS/MS-based metabolic profiling of miR-155 deficient breast cancer cells. Our results revealed the loss of miR-155 hampers glucose uptake and glycolysis, via the down-regulation of glucose transporters and metabolic enzymes including HK2, PKM2, and LDHA. We showed this is due to the down-regulation of cMYC, controlled through phosphoinositide-3-kinase regulatory subunit alpha (PIK3R1)-PDK1/AKT-FOXO3a pathway. UTR analysis of the PIK3R1 and FOXO3a indicated miR-155 directly represses these genes. A stable expression of miR-155 in patient-derived cells (PDCs) showed activated glucose metabolism whereas a stable inhibition of miR-155 reduced in vivo tumor growth with retarded glucose metabolism. Furthermore, analysis of 50 triple-negative breast cancer (TNBC) specimens and specific uptake value (SUV) of PET images revealed a positive correlation between miR-155 level and glucose usage in human breast tumors via PIK3R1-PDK/AKT-FOXO3a-cMYC axis. Collectively, these data demonstrate the miR-155 is a key regulator of glucose metabolism in breast cancer.
Audience Academic
Author Son, Byung Ho
Jung, Jaeyun
Lee, Hee Jin
Sharan, Shyam K
Lee, Eunji
Kim, Hee Jung
Gong, Gyungyup
Lee, Jong Won
Kim, Jisun
Jeon, Sang Min
Chang, Suhwan
Chae, Sun Young
Kim, Sinae
Yoo, Hyun ju
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  organization: Department of Biomedical Sciences, University of Ulsan College of Medicine
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  surname: Jeon
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  organization: College of Pharmacy and Institute of Pharmaceutical Science and Technology, Ajou University
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  email: suhwan.chang@amc.seoul.kr
  organization: Department of Biomedical Sciences, University of Ulsan College of Medicine
BackLink https://www.ncbi.nlm.nih.gov/pubmed/29527004$$D View this record in MEDLINE/PubMed
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Copyright The Author(s) 2018
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  contributor:
    fullname: P Brodersen
SSID ssj0007902
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Snippet MicroRNA is an endogenous, small RNA controlling multiple target genes and playing roles in various biological processes including tumorigenesis. Here, we...
AbstractMicroRNA is an endogenous, small RNA controlling multiple target genes and playing roles in various biological processes including tumorigenesis. Here,...
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StartPage 2982
SubjectTerms 13
3' Untranslated Regions
38/77
631/67/1347
631/67/2327
631/67/395
631/67/70
64
64/60
82/58
96
96/109
96/31
96/95
AKT protein
Animals
Apoptosis
Breast cancer
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Care and treatment
Carrier proteins
Cell Biology
Cell Line, Tumor
Chromatography, Liquid
Development and progression
Female
Forkhead Box Protein O3 - genetics
FOXO3 protein
Gene Expression Regulation, Neoplastic
Genetic aspects
Genetic regulation
Glucose
Glucose - metabolism
Glycolysis
Health aspects
Human Genetics
Humans
Internal Medicine
Kinases
MCF-7 Cells
Medicine
Medicine & Public Health
Metabolism
Mice
MicroRNA
MicroRNAs
MicroRNAs - genetics
miRNA
Neoplasm Transplantation
Oncology
Phosphatidylinositol 3-Kinases - genetics
Proto-Oncogene Proteins c-myc - genetics
Signal Transduction
Tandem Mass Spectrometry
Tumorigenesis
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Title microRNA-155 positively regulates glucose metabolism via PIK3R1-FOXO3a-cMYC axis in breast cancer
URI https://link.springer.com/article/10.1038/s41388-018-0124-4
https://www.ncbi.nlm.nih.gov/pubmed/29527004
https://www.proquest.com/docview/2047226488
https://search.proquest.com/docview/2013102701
https://pubmed.ncbi.nlm.nih.gov/PMC5978802
Volume 37
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