Genome-Wide miRNA Expression Profiling of Molecular Subgroups of Peripheral T-cell Lymphoma.


Journal

Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500

Informations de publication

Date de publication:
01 11 2021
Historique:
received: 11 02 2021
revised: 15 05 2021
accepted: 19 08 2021
pubmed: 25 8 2021
medline: 1 4 2022
entrez: 24 8 2021
Statut: ppublish

Résumé

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas with aggressive clinical behavior. We performed comprehensive miRNA profiling in PTCLs and corresponding normal CD4 We used nCounter (NanoString Inc) for miRNA profiling and validated using Taqman qRT-PCR (Applied Biosystems, Inc). Normal CD4 Effector Th subsets showed distinct miRNA expression with corresponding transcription factor expression (e.g., BCL6/miR-19b, -106, -30d, -26b, in IL21-polarized; GATA3/miR-155, miR-337 in Th2-polarized; and TBX21/miR-181a, -331-3p in Th1-polarized cells). Integration of miRNA signatures suggested activation of TCR and PI3K signaling in IL21-polarized cells, ERK signaling in Th1-polarized cells, and AKT-mTOR signaling in Th2-polarized cells, validated at protein level. In neoplastic counterparts, distinctive miRNAs were identified and confirmed in an independent cohort. Integrative miRNA-mRNA analysis identified a decrease in target transcript abundance leading to deregulation of sphingolipid and Wnt signaling and epigenetic dysregulation in angioimmunoblastic T-cell lymphoma (AITL), while ERK, MAPK, and cell cycle were identified in PTCL subsets, and decreased target transcript abundance was validated in an independent cohort. Elevated expression of miRNAs (miR-126-3p, miR-145-5p) in AITL was associated with poor clinical outcome. Unique miRNAs and deregulated oncogenic pathways are associated with PTCL subtypes. Upregulated miRNA-126-3p and miR-145-5p expression regulate RhoA-GTPase and inhibit T-cell migration, crucial for AITL pathobiology.

Identifiants

pubmed: 34426436
pii: 1078-0432.CCR-21-0573
doi: 10.1158/1078-0432.CCR-21-0573
pmc: PMC8563427
mid: NIHMS1736608
doi:

Substances chimiques

MicroRNAs 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6039-6053

Subventions

Organisme : NCI NIH HHS
ID : U01 CA253218
Pays : United States
Organisme : NCI NIH HHS
ID : UH3 CA206127
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA229100
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA251412
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA136411
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009476
Pays : United States
Organisme : NCI NIH HHS
ID : UH2 CA206127
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA157581
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA036727
Pays : United States

Informations de copyright

©2021 American Association for Cancer Research.

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Auteurs

Waseem Lone (W)

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska.

Alyssa Bouska (A)

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska.

Sunandini Sharma (S)

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska.

Catalina Amador (C)

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska.

Mallick Saumyaranjan (M)

Institute of Pathology, All India Institute of Medical Sciences, New Delhi, India.

Tyler A Herek (TA)

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska.

Tayla B Heavican (TB)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Jiayu Yu (J)

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska.

Soon Thye Lim (ST)

Division of Medical Oncology, National Cancer Centre Singapore/Duke-National University of Singapore (NUS) Medical School, Singapore.

Choon Kiat Ong (CK)

Division of Medical Oncology, National Cancer Centre Singapore/Duke-National University of Singapore (NUS) Medical School, Singapore.

Graham W Slack (GW)

Center for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.

Kerry J Savage (KJ)

Center for Lymphoid Cancer, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.

Andreas Rosenwald (A)

Institute of Pathology, University of Würzburg and Comprehensive Cancer Center Mainfranken, Würzburg, Germany.

German Ott (G)

Department of Clinical Pathology, Robert-Bosch-Krankenhaus and Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.

James R Cook (JR)

Department of Laboratory Medicine, Cleveland Clinic, Cleveland, Ohio.

Andrew L Feldman (AL)

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.

Lisa M Rimsza (LM)

Department of Laboratory Medicine and Pathology, Mayo Clinic, Scottsdale, Arizona.

Timothy W McKeithan (TW)

Department of Pathology, City of Hope National Medical Center, Duarte, California.

Timothy C Greiner (TC)

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska.

Dennis D Weisenburger (DD)

Department of Pathology, City of Hope National Medical Center, Duarte, California.

Federica Melle (F)

European Institute of Oncology IEO IRCCS, Milan, Italy.

Giovanna Motta (G)

European Institute of Oncology IEO IRCCS, Milan, Italy.

Stefano Pileri (S)

European Institute of Oncology IEO IRCCS, Milan, Italy.

Julie M Vose (JM)

Division of Hematology and Oncology, University of Nebraska Medical Center, Omaha, Nebraska.

Wing C Chan (WC)

Department of Pathology, City of Hope National Medical Center, Duarte, California.

Javeed Iqbal (J)

Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska. jiqbal@unmc.edu.

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