LINC00520 is induced by Src, STAT3, and PI3K and plays a functional role in breast cancer

Whitney S. Henry; David G. Hendrickson; Francisco Beca; Benjamin Glass; Marianne Lindahl-Allen; Lizhi He; Zhe Ji; Kevin Struhl; Andrew H. Beck; John L. Rinn; Alex Toker

doi:10.18632/oncotarget.11962

LINC00520 is induced by Src, STAT3, and PI3K and plays a functional role in breast cancer

Whitney S. Henry, David G. Hendrickson, Francisco Beca, Benjamin Glass, Marianne Lindahl-Allen, Lizhi He, Zhe Ji, Kevin Struhl, Andrew H. Beck, John L. Rinn, Alex Toker^*

^*Corresponding author for this work

Pharmacology

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

Abstract

Long non-coding RNAs (lncRNAs) have been implicated in normal cellular homeostasis as well as pathophysiological conditions, including cancer. Here we performed global gene expression profiling of mammary epithelial cells transformed by oncogenic v-Src, and identified a large subset of uncharacterized lncRNAs potentially involved in breast cancer development. Specifically, our analysis revealed a novel lncRNA, LINC00520 that is upregulated upon ectopic expression of oncogenic v-Src, in a manner that is dependent on the transcription factor STAT3. Similarly, LINC00520 is also increased in mammary epithelial cells transformed by oncogenic PI3K and its expression is decreased upon knockdown of mutant PIK3CA. Additional expression profiling highlight that LINC00520 is elevated in a subset of human breast carcinomas, with preferential enrichment in the basal-like molecular subtype. ShRNAmediated depletion of LINC00520 results in decreased cell migration and loss of invasive structures in 3D. RNA sequencing analysis uncovers several genes that are differentially expressed upon ectopic expression of LINC00520, a significant subset of which are also induced in v-Src-transformed MCF10A cells. Together, these findings characterize LINC00520 as a lncRNA that is regulated by oncogenic Src, PIK3CA and STAT3, and which may contribute to the molecular etiology of breast cancer.

Original language	English (US)
Pages (from-to)	81981-81994
Number of pages	14
Journal	Oncotarget
Volume	7
Issue number	50
DOIs	https://doi.org/10.18632/oncotarget.11962
State	Published - 2016

Funding

The authors acknowledge the generous advice and support by members of the Toker and Rinn laboratories; Sandra McAllister and Carl Novina for discussions and advice; and Jonathan Backer for the isogenic MDAMB-231 cell lines.This work was supported in part by grants from the National Institutes of Health (A.T., R21CA181143), (A.B., K22LM011931), (K.S., CA 107486), Howard Hughes Medical Institute (W.I.H, HHMI International Student Research Fellowship) and Damon Runyon Cancer Research Foundation (D.H., Damon Runyon Postdoctoral Research Fellow).

Keywords

Breast cancer
LINC00520
LncRNA
PI3K
Src

ASJC Scopus subject areas

Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.18632/oncotarget.11962

Cite this

@article{d57a26b0ee4949638bf98dfb2d045a7f,

title = "LINC00520 is induced by Src, STAT3, and PI3K and plays a functional role in breast cancer",

abstract = "Long non-coding RNAs (lncRNAs) have been implicated in normal cellular homeostasis as well as pathophysiological conditions, including cancer. Here we performed global gene expression profiling of mammary epithelial cells transformed by oncogenic v-Src, and identified a large subset of uncharacterized lncRNAs potentially involved in breast cancer development. Specifically, our analysis revealed a novel lncRNA, LINC00520 that is upregulated upon ectopic expression of oncogenic v-Src, in a manner that is dependent on the transcription factor STAT3. Similarly, LINC00520 is also increased in mammary epithelial cells transformed by oncogenic PI3K and its expression is decreased upon knockdown of mutant PIK3CA. Additional expression profiling highlight that LINC00520 is elevated in a subset of human breast carcinomas, with preferential enrichment in the basal-like molecular subtype. ShRNAmediated depletion of LINC00520 results in decreased cell migration and loss of invasive structures in 3D. RNA sequencing analysis uncovers several genes that are differentially expressed upon ectopic expression of LINC00520, a significant subset of which are also induced in v-Src-transformed MCF10A cells. Together, these findings characterize LINC00520 as a lncRNA that is regulated by oncogenic Src, PIK3CA and STAT3, and which may contribute to the molecular etiology of breast cancer.",

keywords = "Breast cancer, LINC00520, LncRNA, PI3K, Src",

author = "Henry, {Whitney S.} and Hendrickson, {David G.} and Francisco Beca and Benjamin Glass and Marianne Lindahl-Allen and Lizhi He and Zhe Ji and Kevin Struhl and Beck, {Andrew H.} and Rinn, {John L.} and Alex Toker",

note = "Funding Information: The authors acknowledge the generous advice and support by members of the Toker and Rinn laboratories; Sandra McAllister and Carl Novina for discussions and advice; and Jonathan Backer for the isogenic MDAMB-231 cell lines.This work was supported in part by grants from the National Institutes of Health (A.T., R21CA181143), (A.B., K22LM011931), (K.S., CA 107486), Howard Hughes Medical Institute (W.I.H, HHMI International Student Research Fellowship) and Damon Runyon Cancer Research Foundation (D.H., Damon Runyon Postdoctoral Research Fellow).",

year = "2016",

doi = "10.18632/oncotarget.11962",

language = "English (US)",

volume = "7",

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T1 - LINC00520 is induced by Src, STAT3, and PI3K and plays a functional role in breast cancer

AU - Henry, Whitney S.

AU - Hendrickson, David G.

AU - Beca, Francisco

AU - Glass, Benjamin

AU - Lindahl-Allen, Marianne

AU - He, Lizhi

AU - Ji, Zhe

AU - Struhl, Kevin

AU - Beck, Andrew H.

AU - Rinn, John L.

AU - Toker, Alex

N1 - Funding Information: The authors acknowledge the generous advice and support by members of the Toker and Rinn laboratories; Sandra McAllister and Carl Novina for discussions and advice; and Jonathan Backer for the isogenic MDAMB-231 cell lines.This work was supported in part by grants from the National Institutes of Health (A.T., R21CA181143), (A.B., K22LM011931), (K.S., CA 107486), Howard Hughes Medical Institute (W.I.H, HHMI International Student Research Fellowship) and Damon Runyon Cancer Research Foundation (D.H., Damon Runyon Postdoctoral Research Fellow).

PY - 2016

Y1 - 2016

N2 - Long non-coding RNAs (lncRNAs) have been implicated in normal cellular homeostasis as well as pathophysiological conditions, including cancer. Here we performed global gene expression profiling of mammary epithelial cells transformed by oncogenic v-Src, and identified a large subset of uncharacterized lncRNAs potentially involved in breast cancer development. Specifically, our analysis revealed a novel lncRNA, LINC00520 that is upregulated upon ectopic expression of oncogenic v-Src, in a manner that is dependent on the transcription factor STAT3. Similarly, LINC00520 is also increased in mammary epithelial cells transformed by oncogenic PI3K and its expression is decreased upon knockdown of mutant PIK3CA. Additional expression profiling highlight that LINC00520 is elevated in a subset of human breast carcinomas, with preferential enrichment in the basal-like molecular subtype. ShRNAmediated depletion of LINC00520 results in decreased cell migration and loss of invasive structures in 3D. RNA sequencing analysis uncovers several genes that are differentially expressed upon ectopic expression of LINC00520, a significant subset of which are also induced in v-Src-transformed MCF10A cells. Together, these findings characterize LINC00520 as a lncRNA that is regulated by oncogenic Src, PIK3CA and STAT3, and which may contribute to the molecular etiology of breast cancer.

AB - Long non-coding RNAs (lncRNAs) have been implicated in normal cellular homeostasis as well as pathophysiological conditions, including cancer. Here we performed global gene expression profiling of mammary epithelial cells transformed by oncogenic v-Src, and identified a large subset of uncharacterized lncRNAs potentially involved in breast cancer development. Specifically, our analysis revealed a novel lncRNA, LINC00520 that is upregulated upon ectopic expression of oncogenic v-Src, in a manner that is dependent on the transcription factor STAT3. Similarly, LINC00520 is also increased in mammary epithelial cells transformed by oncogenic PI3K and its expression is decreased upon knockdown of mutant PIK3CA. Additional expression profiling highlight that LINC00520 is elevated in a subset of human breast carcinomas, with preferential enrichment in the basal-like molecular subtype. ShRNAmediated depletion of LINC00520 results in decreased cell migration and loss of invasive structures in 3D. RNA sequencing analysis uncovers several genes that are differentially expressed upon ectopic expression of LINC00520, a significant subset of which are also induced in v-Src-transformed MCF10A cells. Together, these findings characterize LINC00520 as a lncRNA that is regulated by oncogenic Src, PIK3CA and STAT3, and which may contribute to the molecular etiology of breast cancer.

KW - Breast cancer

KW - LINC00520

KW - LncRNA

KW - PI3K

KW - Src

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AN - SCOPUS:85004081563

SN - 1949-2553

VL - 7

SP - 81981

EP - 81994

JO - Oncotarget

JF - Oncotarget

IS - 50

ER -

LINC00520 is induced by Src, STAT3, and PI3K and plays a functional role in breast cancer

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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