Long noncoding RNA EMS connects c-Myc to cell cycle control and tumorigenesis

Chenfeng Wang; Yang Yang; Guang Zhang; Jingxin Li; Xianning Wu; Xiaoling Ma; Ge Shan; Yide Mei

doi:10.1073/pnas.1903432116

Long noncoding RNA EMS connects c-Myc to cell cycle control and tumorigenesis

Proc Natl Acad Sci U S A. 2019 Jul 16;116(29):14620-14629. doi: 10.1073/pnas.1903432116. Epub 2019 Jul 1.

Authors

Chenfeng Wang^{1

2}, Yang Yang^{1

2}, Guang Zhang^{1

2}, Jingxin Li^{1

2}, Xianning Wu³, Xiaoling Ma⁴, Ge Shan^{1

2}, Yide Mei^{5

2}

Affiliations

¹ Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, First Affiliated Hospital of University of Science and Technology of China, School of Life Sciences, University of Science and Technology of China (USTC), 230027 Hefei, Anhui, China.
² Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, USTC, 230027 Hefei, Anhui, China.
³ Department of Thoracic Surgery, First Affiliated Hospital of USTC, USTC, 230027 Hefei, Anhui, China.
⁴ Department of Laboratory Medicine, First Affiliated Hospital of USTC, USTC, 230027 Hefei, Anhui, China.
⁵ Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, First Affiliated Hospital of University of Science and Technology of China, School of Life Sciences, University of Science and Technology of China (USTC), 230027 Hefei, Anhui, China; meiyide@ustc.edu.cn.

Abstract

Deregulated expression of c-Myc is an important molecular hallmark of cancer. The oncogenic function of c-Myc has been largely attributed to its intrinsic nature as a master transcription factor. Here, we report the long noncoding RNA (lncRNA) E2F1 messenger RNA (mRNA) stabilizing factor (EMS) as a direct c-Myc transcriptional target. EMS functions as an oncogenic molecule by promoting G1/S cell cycle progression. Mechanistically, EMS cooperates with the RNA binding protein RALY to stabilize E2F1 mRNA, and thereby increases E2F1 expression. Furthermore, EMS is able to connect c-Myc to cell cycle control and tumorigenesis via modulating E2F1 mRNA stability. Together, these findings reveal a previously unappreciated mechanism through which c-Myc induces E2F1 expression and also implicate EMS as an important player in the regulation of c-Myc function.

Keywords: E2F1; c-Myc; lncRNA; tumorigenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

A549 Cells
Animals
Carcinogenesis / genetics*
E2F1 Transcription Factor / genetics
G1 Phase Cell Cycle Checkpoints / genetics*
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
HEK293 Cells
Heterogeneous-Nuclear Ribonucleoprotein Group C / metabolism
Humans
Mice
Neoplasms / genetics*
Neoplasms / pathology
Proto-Oncogene Proteins c-myc / genetics
Proto-Oncogene Proteins c-myc / metabolism*
RNA Stability / genetics
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism
RNA, Messenger / metabolism
RNA, Small Interfering / metabolism
Xenograft Model Antitumor Assays

Substances

E2F1 Transcription Factor
E2F1 protein, human
Heterogeneous-Nuclear Ribonucleoprotein Group C
MYC protein, human
Proto-Oncogene Proteins c-myc
RALY protein, human
RNA, Long Noncoding
RNA, Messenger
RNA, Small Interfering