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 journalReview articlepeer-review

71 Citations (Scopus)
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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 languageEnglish
Article number234
Number of pages15
Issue number2
Early online date16 Feb 2019
Publication statusPublished - 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.


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


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