TY - JOUR
T1 - Exploring lncRNA-mediated regulatory networks in endometrial cancer cells and the tumor microenvironment
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
Y1 - 2019/2/16
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
UR - http://www.scopus.com/inward/record.url?scp=85062502936&partnerID=8YFLogxK
U2 - 10.3390/cancers11020234
DO - 10.3390/cancers11020234
M3 - Review article
AN - SCOPUS:85062502936
VL - 11
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 2
M1 - 234
ER -