Exploring lncRNA-mediated regulatory networks in endometrial cancer cells and the tumor microenvironment: Advances and challenges

Peixin Dong; Ying Xiong; Junming Yue; Sharon J.B. Hanley; Noriko Kobayashi; Yukiharu Todo; Hidemichi Watari

doi:10.3390/cancers11020234

Exploring lncRNA-mediated regulatory networks in endometrial cancer cells and the tumor microenvironment: Advances and challenges

Peixin Dong, Ying Xiong, Junming Yue, Sharon J.B. Hanley, Noriko Kobayashi, Yukiharu Todo, Hidemichi Watari^*

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

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Abstract

Recent studies have revealed both the promise and challenges of targeting long non-coding RNAs (lncRNAs) to diagnose and treat endometrial cancer (EC). LncRNAs are upregulated or downregulated in ECs compared to normal tissues and their dysregulation has been linked to tumor grade, FIGO stage, the depth of myometrial invasion, lymph node metastasis and patient survival. Tumor suppressive lncRNAs (GAS5, MEG3, FER1L4 and LINC00672) and oncogenic lncRNAs (CCAT2, BANCR, NEAT1, MALAT1, H19 and Linc-RoR) have been identified as upstream modulators or downstream effectors of major signaling pathways influencing EC metastasis, including the PTEN/PI3K/AKT/mTOR, RAS/RAF/MEK/ERK, WNT/β-catenin and p53 signaling pathways. TUG1 and TDRG1 stimulate the VEGF-A pathway. PCGEM1 is implicated in activating the JAK/STAT3 pathway. Here, we present an overview of the expression pattern, prognostic value, biological function of lncRNAs in EC cells and their roles within the tumor microenvironment, focusing on the influence of lncRNAs on established EC-relevant pathways. We also describe the emerging classification of EC subtypes based on their lncRNA signature and discuss the clinical implications of lncRNAs as valuable biomarkers for EC diagnosis and potential targets for EC treatment.

Original language	English
Article number	234
Number of pages	15
Journal	Cancers
Volume	11
Issue number	2
Early online date	16 Feb 2019
DOIs	https://doi.org/10.3390/cancers11020234
Publication status	Published - 16 Feb 2019

Bibliographical note

Funding Information:
Funding: This work was supported by a grant from JSPS Grant-in-Aid for Scientific Research (C) (16K11123 and 18K09278), the Science and Technology Planning Project of Guangdong Province, China (2014A020212124) and an NIH/NCI grant 1R21CA216585-01A1 to Junming Yue.
Acknowledgments: We thank Zhujie Xu for her full contribution in preparing the figures.

Keywords

Endometrial cancer
Epigenetics
Long non-coding RNA
microRNA
Prognostic biomarker
Regulatory mechanism
Therapeutic target
Tumor microenvironment

UN SDGs

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

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Final published version, 1.03 MBLicence: CC BY

Cite this

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title = "Exploring lncRNA-mediated regulatory networks in endometrial cancer cells and the tumor microenvironment: Advances and challenges",

abstract = "Recent studies have revealed both the promise and challenges of targeting long non-coding RNAs (lncRNAs) to diagnose and treat endometrial cancer (EC). LncRNAs are upregulated or downregulated in ECs compared to normal tissues and their dysregulation has been linked to tumor grade, FIGO stage, the depth of myometrial invasion, lymph node metastasis and patient survival. Tumor suppressive lncRNAs (GAS5, MEG3, FER1L4 and LINC00672) and oncogenic lncRNAs (CCAT2, BANCR, NEAT1, MALAT1, H19 and Linc-RoR) have been identified as upstream modulators or downstream effectors of major signaling pathways influencing EC metastasis, including the PTEN/PI3K/AKT/mTOR, RAS/RAF/MEK/ERK, WNT/β-catenin and p53 signaling pathways. TUG1 and TDRG1 stimulate the VEGF-A pathway. PCGEM1 is implicated in activating the JAK/STAT3 pathway. Here, we present an overview of the expression pattern, prognostic value, biological function of lncRNAs in EC cells and their roles within the tumor microenvironment, focusing on the influence of lncRNAs on established EC-relevant pathways. We also describe the emerging classification of EC subtypes based on their lncRNA signature and discuss the clinical implications of lncRNAs as valuable biomarkers for EC diagnosis and potential targets for EC treatment.",

keywords = "Endometrial cancer, Epigenetics, Long non-coding RNA, microRNA, Prognostic biomarker, Regulatory mechanism, Therapeutic target, Tumor microenvironment",

author = "Peixin Dong and Ying Xiong and Junming Yue and Hanley, {Sharon J.B.} and Noriko Kobayashi and Yukiharu Todo and Hidemichi Watari",

note = "Funding Information: Funding: This work was supported by a grant from JSPS Grant-in-Aid for Scientific Research (C) (16K11123 and 18K09278), the Science and Technology Planning Project of Guangdong Province, China (2014A020212124) and an NIH/NCI grant 1R21CA216585-01A1 to Junming Yue. Acknowledgments: We thank Zhujie Xu for her full contribution in preparing the figures.",

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T2 - Advances and challenges

AU - Dong, Peixin

AU - Xiong, Ying

AU - Yue, Junming

AU - Hanley, Sharon J.B.

AU - Kobayashi, Noriko

AU - Todo, Yukiharu

AU - Watari, Hidemichi

N1 - Funding Information: Funding: This work was supported by a grant from JSPS Grant-in-Aid for Scientific Research (C) (16K11123 and 18K09278), the Science and Technology Planning Project of Guangdong Province, China (2014A020212124) and an NIH/NCI grant 1R21CA216585-01A1 to Junming Yue. Acknowledgments: We thank Zhujie Xu for her full contribution in preparing the figures.

PY - 2019/2/16

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N2 - Recent studies have revealed both the promise and challenges of targeting long non-coding RNAs (lncRNAs) to diagnose and treat endometrial cancer (EC). LncRNAs are upregulated or downregulated in ECs compared to normal tissues and their dysregulation has been linked to tumor grade, FIGO stage, the depth of myometrial invasion, lymph node metastasis and patient survival. Tumor suppressive lncRNAs (GAS5, MEG3, FER1L4 and LINC00672) and oncogenic lncRNAs (CCAT2, BANCR, NEAT1, MALAT1, H19 and Linc-RoR) have been identified as upstream modulators or downstream effectors of major signaling pathways influencing EC metastasis, including the PTEN/PI3K/AKT/mTOR, RAS/RAF/MEK/ERK, WNT/β-catenin and p53 signaling pathways. TUG1 and TDRG1 stimulate the VEGF-A pathway. PCGEM1 is implicated in activating the JAK/STAT3 pathway. Here, we present an overview of the expression pattern, prognostic value, biological function of lncRNAs in EC cells and their roles within the tumor microenvironment, focusing on the influence of lncRNAs on established EC-relevant pathways. We also describe the emerging classification of EC subtypes based on their lncRNA signature and discuss the clinical implications of lncRNAs as valuable biomarkers for EC diagnosis and potential targets for EC treatment.

AB - Recent studies have revealed both the promise and challenges of targeting long non-coding RNAs (lncRNAs) to diagnose and treat endometrial cancer (EC). LncRNAs are upregulated or downregulated in ECs compared to normal tissues and their dysregulation has been linked to tumor grade, FIGO stage, the depth of myometrial invasion, lymph node metastasis and patient survival. Tumor suppressive lncRNAs (GAS5, MEG3, FER1L4 and LINC00672) and oncogenic lncRNAs (CCAT2, BANCR, NEAT1, MALAT1, H19 and Linc-RoR) have been identified as upstream modulators or downstream effectors of major signaling pathways influencing EC metastasis, including the PTEN/PI3K/AKT/mTOR, RAS/RAF/MEK/ERK, WNT/β-catenin and p53 signaling pathways. TUG1 and TDRG1 stimulate the VEGF-A pathway. PCGEM1 is implicated in activating the JAK/STAT3 pathway. Here, we present an overview of the expression pattern, prognostic value, biological function of lncRNAs in EC cells and their roles within the tumor microenvironment, focusing on the influence of lncRNAs on established EC-relevant pathways. We also describe the emerging classification of EC subtypes based on their lncRNA signature and discuss the clinical implications of lncRNAs as valuable biomarkers for EC diagnosis and potential targets for EC treatment.

KW - Endometrial cancer

KW - Epigenetics

KW - Long non-coding RNA

KW - microRNA

KW - Prognostic biomarker

KW - Regulatory mechanism

KW - Therapeutic target

KW - Tumor microenvironment

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U2 - 10.3390/cancers11020234

DO - 10.3390/cancers11020234

M3 - Review article

AN - SCOPUS:85062502936

SN - 2072-6694

VL - 11

JO - Cancers

JF - Cancers

IS - 2

M1 - 234

ER -

Exploring lncRNA-mediated regulatory networks in endometrial cancer cells and the tumor microenvironment: Advances and challenges

Abstract

Bibliographical note

Keywords

UN SDGs

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