Quantitative proteomics reveals that miR-155 regulates the PI3K-AKT pathway in diffuse large B-cell lymphoma

Xin Huang, Yulei Shen, Miao Liu, Chengfeng Bi, Chunsun Jiang, Javeed Iqbal, Timothy W. McKeithan, Wing C. Chan, Shi Jian Ding, Kai Fu

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

The aberrant expression of microRNA-155 (miR-155), which has emerged as having a significant impact on the biological characteristics of lymphocytes, plays important roles in B-cell malignancies, such as diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common non-Hodgkin's lymphoma in the adult population, accounting for approximately 40% of newly diagnosed non-Hodgkin's lymphoma cases globally. To determine the specific function of miR-155, a quantitative proteomics approach was applied to examine the inhibitory effects of miR-155 on protein synthesis in DLBCL cells. PIK3R1 (p85α), a negative regulator of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, was identified as a direct target of miR-155. A luciferase reporter was repressed through the direct interaction of miR-155 and the p85α 3′-untranslated region, and overexpression of miR-155 down-regulated both the transcription and translation of p85α. The PI3K-AKT signaling pathway was highly activated by the sustained overexpression of miR-155 in DHL16 cells, whereas knockdown of miR-155 in OCI-Ly3 cells diminished AKT activity. Taken together, our results reveal a novel target involved in miR-155 biological characteristics and provide a molecular link between the overexpression of miR-155 and the activation of PI3K-AKT in DLBCL.

Original languageEnglish (US)
Pages (from-to)26-33
Number of pages8
JournalAmerican Journal of Pathology
Volume181
Issue number1
DOIs
StatePublished - Jul 1 2012

Fingerprint

Phosphatidylinositol 3-Kinase
Lymphoma, Large B-Cell, Diffuse
MicroRNAs
Proteomics
Non-Hodgkin's Lymphoma
3' Untranslated Regions
Luciferases
B-Lymphocytes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Quantitative proteomics reveals that miR-155 regulates the PI3K-AKT pathway in diffuse large B-cell lymphoma. / Huang, Xin; Shen, Yulei; Liu, Miao; Bi, Chengfeng; Jiang, Chunsun; Iqbal, Javeed; McKeithan, Timothy W.; Chan, Wing C.; Ding, Shi Jian; Fu, Kai.

In: American Journal of Pathology, Vol. 181, No. 1, 01.07.2012, p. 26-33.

Research output: Contribution to journalArticle

Huang, Xin ; Shen, Yulei ; Liu, Miao ; Bi, Chengfeng ; Jiang, Chunsun ; Iqbal, Javeed ; McKeithan, Timothy W. ; Chan, Wing C. ; Ding, Shi Jian ; Fu, Kai. / Quantitative proteomics reveals that miR-155 regulates the PI3K-AKT pathway in diffuse large B-cell lymphoma. In: American Journal of Pathology. 2012 ; Vol. 181, No. 1. pp. 26-33.
@article{b6d7ced816994e28b551325b64349f1a,
title = "Quantitative proteomics reveals that miR-155 regulates the PI3K-AKT pathway in diffuse large B-cell lymphoma",
abstract = "The aberrant expression of microRNA-155 (miR-155), which has emerged as having a significant impact on the biological characteristics of lymphocytes, plays important roles in B-cell malignancies, such as diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common non-Hodgkin's lymphoma in the adult population, accounting for approximately 40{\%} of newly diagnosed non-Hodgkin's lymphoma cases globally. To determine the specific function of miR-155, a quantitative proteomics approach was applied to examine the inhibitory effects of miR-155 on protein synthesis in DLBCL cells. PIK3R1 (p85α), a negative regulator of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, was identified as a direct target of miR-155. A luciferase reporter was repressed through the direct interaction of miR-155 and the p85α 3′-untranslated region, and overexpression of miR-155 down-regulated both the transcription and translation of p85α. The PI3K-AKT signaling pathway was highly activated by the sustained overexpression of miR-155 in DHL16 cells, whereas knockdown of miR-155 in OCI-Ly3 cells diminished AKT activity. Taken together, our results reveal a novel target involved in miR-155 biological characteristics and provide a molecular link between the overexpression of miR-155 and the activation of PI3K-AKT in DLBCL.",
author = "Xin Huang and Yulei Shen and Miao Liu and Chengfeng Bi and Chunsun Jiang and Javeed Iqbal and McKeithan, {Timothy W.} and Chan, {Wing C.} and Ding, {Shi Jian} and Kai Fu",
year = "2012",
month = "7",
day = "1",
doi = "10.1016/j.ajpath.2012.03.013",
language = "English (US)",
volume = "181",
pages = "26--33",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Quantitative proteomics reveals that miR-155 regulates the PI3K-AKT pathway in diffuse large B-cell lymphoma

AU - Huang, Xin

AU - Shen, Yulei

AU - Liu, Miao

AU - Bi, Chengfeng

AU - Jiang, Chunsun

AU - Iqbal, Javeed

AU - McKeithan, Timothy W.

AU - Chan, Wing C.

AU - Ding, Shi Jian

AU - Fu, Kai

PY - 2012/7/1

Y1 - 2012/7/1

N2 - The aberrant expression of microRNA-155 (miR-155), which has emerged as having a significant impact on the biological characteristics of lymphocytes, plays important roles in B-cell malignancies, such as diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common non-Hodgkin's lymphoma in the adult population, accounting for approximately 40% of newly diagnosed non-Hodgkin's lymphoma cases globally. To determine the specific function of miR-155, a quantitative proteomics approach was applied to examine the inhibitory effects of miR-155 on protein synthesis in DLBCL cells. PIK3R1 (p85α), a negative regulator of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, was identified as a direct target of miR-155. A luciferase reporter was repressed through the direct interaction of miR-155 and the p85α 3′-untranslated region, and overexpression of miR-155 down-regulated both the transcription and translation of p85α. The PI3K-AKT signaling pathway was highly activated by the sustained overexpression of miR-155 in DHL16 cells, whereas knockdown of miR-155 in OCI-Ly3 cells diminished AKT activity. Taken together, our results reveal a novel target involved in miR-155 biological characteristics and provide a molecular link between the overexpression of miR-155 and the activation of PI3K-AKT in DLBCL.

AB - The aberrant expression of microRNA-155 (miR-155), which has emerged as having a significant impact on the biological characteristics of lymphocytes, plays important roles in B-cell malignancies, such as diffuse large B-cell lymphoma (DLBCL). DLBCL is the most common non-Hodgkin's lymphoma in the adult population, accounting for approximately 40% of newly diagnosed non-Hodgkin's lymphoma cases globally. To determine the specific function of miR-155, a quantitative proteomics approach was applied to examine the inhibitory effects of miR-155 on protein synthesis in DLBCL cells. PIK3R1 (p85α), a negative regulator of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, was identified as a direct target of miR-155. A luciferase reporter was repressed through the direct interaction of miR-155 and the p85α 3′-untranslated region, and overexpression of miR-155 down-regulated both the transcription and translation of p85α. The PI3K-AKT signaling pathway was highly activated by the sustained overexpression of miR-155 in DHL16 cells, whereas knockdown of miR-155 in OCI-Ly3 cells diminished AKT activity. Taken together, our results reveal a novel target involved in miR-155 biological characteristics and provide a molecular link between the overexpression of miR-155 and the activation of PI3K-AKT in DLBCL.

UR - http://www.scopus.com/inward/record.url?scp=84862660781&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862660781&partnerID=8YFLogxK

U2 - 10.1016/j.ajpath.2012.03.013

DO - 10.1016/j.ajpath.2012.03.013

M3 - Article

VL - 181

SP - 26

EP - 33

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 1

ER -