A novel hypoxic long noncoding RNA KB-1980E6.3 maintains breast cancer stem cell stemness via interacting with IGF2BP1 to facilitate c-Myc mRNA stability

Pengpeng Zhu; Fang He; Yixuan Hou; Gang Tu; Qiao Li; Ting Jin; Huan Zeng; Yilu Qin; Xueying Wan; Yina Qiao; Yuxiang Qiu; Yong Teng; Manran Liu

doi:10.1038/s41388-020-01638-9

A novel hypoxic long noncoding RNA KB-1980E6.3 maintains breast cancer stem cell stemness via interacting with IGF2BP1 to facilitate c-Myc mRNA stability

Pengpeng Zhu, Fang He, Yixuan Hou, Gang Tu, Qiao Li, Ting Jin, Huan Zeng, Yilu Qin, Xueying Wan, Yina Qiao, Yuxiang Qiu, Yong Teng, Manran Liu

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

110 Scopus citations

Abstract

The hostile hypoxic microenvironment takes primary responsibility for the rapid expansion of breast cancer tumors. However, the underlying mechanism is not fully understood. Here, using RNA sequencing (RNA-seq) analysis, we identified a hypoxia-induced long noncoding RNA (lncRNA) KB-1980E6.3, which is aberrantly upregulated in clinical breast cancer tissues and closely correlated with poor prognosis of breast cancer patients. The enhanced lncRNA KB-1980E6.3 facilitates breast cancer stem cells (BCSCs) self-renewal and tumorigenesis under hypoxic microenvironment both in vitro and in vivo. Mechanistically, lncRNA KB-1980E6.3 recruited insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to form a lncRNA KB-1980E6.3/IGF2BP1/c-Myc signaling axis that retained the stability of c-Myc mRNA through increasing binding of IGF2BP1 with m6A-modified c-Myc coding region instability determinant (CRD) mRNA. In conclusion, we confirm that lncRNA KB-1980E6.3 maintains the stemness of BCSCs through lncRNA KB-1980E6.3/IGF2BP1/c-Myc axis and suggest that disrupting this axis might provide a new therapeutic target for refractory hypoxic tumors.

Original language	English (US)
Pages (from-to)	1609-1627
Number of pages	19
Journal	Oncogene
Volume	40
Issue number	9
DOIs	https://doi.org/10.1038/s41388-020-01638-9
State	Published - Mar 4 2021
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

UN SDGs

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

Access to Document

10.1038/s41388-020-01638-9

Cite this

@article{0f21ad08b54b421f8f1c111e8ba3e69c,

title = "A novel hypoxic long noncoding RNA KB-1980E6.3 maintains breast cancer stem cell stemness via interacting with IGF2BP1 to facilitate c-Myc mRNA stability",

abstract = "The hostile hypoxic microenvironment takes primary responsibility for the rapid expansion of breast cancer tumors. However, the underlying mechanism is not fully understood. Here, using RNA sequencing (RNA-seq) analysis, we identified a hypoxia-induced long noncoding RNA (lncRNA) KB-1980E6.3, which is aberrantly upregulated in clinical breast cancer tissues and closely correlated with poor prognosis of breast cancer patients. The enhanced lncRNA KB-1980E6.3 facilitates breast cancer stem cells (BCSCs) self-renewal and tumorigenesis under hypoxic microenvironment both in vitro and in vivo. Mechanistically, lncRNA KB-1980E6.3 recruited insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to form a lncRNA KB-1980E6.3/IGF2BP1/c-Myc signaling axis that retained the stability of c-Myc mRNA through increasing binding of IGF2BP1 with m6A-modified c-Myc coding region instability determinant (CRD) mRNA. In conclusion, we confirm that lncRNA KB-1980E6.3 maintains the stemness of BCSCs through lncRNA KB-1980E6.3/IGF2BP1/c-Myc axis and suggest that disrupting this axis might provide a new therapeutic target for refractory hypoxic tumors.",

author = "Pengpeng Zhu and Fang He and Yixuan Hou and Gang Tu and Qiao Li and Ting Jin and Huan Zeng and Yilu Qin and Xueying Wan and Yina Qiao and Yuxiang Qiu and Yong Teng and Manran Liu",

note = "Funding Information: Acknowledgements This work was supported in part by National Natural Science Foundation of China (NSFC 81874199, NSFC 31671481, and NSFC 81472476). We would like to thank Reid Loveless for his help in English language editing. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

month = mar,

day = "4",

doi = "10.1038/s41388-020-01638-9",

language = "English (US)",

volume = "40",

pages = "1609--1627",

journal = "Oncogene",

issn = "0950-9232",

publisher = "Nature Publishing Group",

number = "9",

}

TY - JOUR

T1 - A novel hypoxic long noncoding RNA KB-1980E6.3 maintains breast cancer stem cell stemness via interacting with IGF2BP1 to facilitate c-Myc mRNA stability

AU - Zhu, Pengpeng

AU - He, Fang

AU - Hou, Yixuan

AU - Tu, Gang

AU - Li, Qiao

AU - Jin, Ting

AU - Zeng, Huan

AU - Qin, Yilu

AU - Wan, Xueying

AU - Qiao, Yina

AU - Qiu, Yuxiang

AU - Teng, Yong

AU - Liu, Manran

N1 - Funding Information: Acknowledgements This work was supported in part by National Natural Science Foundation of China (NSFC 81874199, NSFC 31671481, and NSFC 81472476). We would like to thank Reid Loveless for his help in English language editing. Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature Limited.

PY - 2021/3/4

Y1 - 2021/3/4

N2 - The hostile hypoxic microenvironment takes primary responsibility for the rapid expansion of breast cancer tumors. However, the underlying mechanism is not fully understood. Here, using RNA sequencing (RNA-seq) analysis, we identified a hypoxia-induced long noncoding RNA (lncRNA) KB-1980E6.3, which is aberrantly upregulated in clinical breast cancer tissues and closely correlated with poor prognosis of breast cancer patients. The enhanced lncRNA KB-1980E6.3 facilitates breast cancer stem cells (BCSCs) self-renewal and tumorigenesis under hypoxic microenvironment both in vitro and in vivo. Mechanistically, lncRNA KB-1980E6.3 recruited insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to form a lncRNA KB-1980E6.3/IGF2BP1/c-Myc signaling axis that retained the stability of c-Myc mRNA through increasing binding of IGF2BP1 with m6A-modified c-Myc coding region instability determinant (CRD) mRNA. In conclusion, we confirm that lncRNA KB-1980E6.3 maintains the stemness of BCSCs through lncRNA KB-1980E6.3/IGF2BP1/c-Myc axis and suggest that disrupting this axis might provide a new therapeutic target for refractory hypoxic tumors.

AB - The hostile hypoxic microenvironment takes primary responsibility for the rapid expansion of breast cancer tumors. However, the underlying mechanism is not fully understood. Here, using RNA sequencing (RNA-seq) analysis, we identified a hypoxia-induced long noncoding RNA (lncRNA) KB-1980E6.3, which is aberrantly upregulated in clinical breast cancer tissues and closely correlated with poor prognosis of breast cancer patients. The enhanced lncRNA KB-1980E6.3 facilitates breast cancer stem cells (BCSCs) self-renewal and tumorigenesis under hypoxic microenvironment both in vitro and in vivo. Mechanistically, lncRNA KB-1980E6.3 recruited insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) to form a lncRNA KB-1980E6.3/IGF2BP1/c-Myc signaling axis that retained the stability of c-Myc mRNA through increasing binding of IGF2BP1 with m6A-modified c-Myc coding region instability determinant (CRD) mRNA. In conclusion, we confirm that lncRNA KB-1980E6.3 maintains the stemness of BCSCs through lncRNA KB-1980E6.3/IGF2BP1/c-Myc axis and suggest that disrupting this axis might provide a new therapeutic target for refractory hypoxic tumors.

UR - http://www.scopus.com/inward/record.url?scp=85100100594&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85100100594&partnerID=8YFLogxK

U2 - 10.1038/s41388-020-01638-9

DO - 10.1038/s41388-020-01638-9

M3 - Article

C2 - 33469161

AN - SCOPUS:85100100594

SN - 0950-9232

VL - 40

SP - 1609

EP - 1627

JO - Oncogene

JF - Oncogene

IS - 9

ER -

A novel hypoxic long noncoding RNA KB-1980E6.3 maintains breast cancer stem cell stemness via interacting with IGF2BP1 to facilitate c-Myc mRNA stability

Abstract

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this