Exploring the role of non-coding RNA mediated regulation of signaling pathways in endometrial cancer

Abstract

Endometrial cancer (EC) is the most common gynecological cancer, with rising mortality rates. Targeting non-coding RNAs (ncRNAs) to diagnose and cure endometrial cancer has shown both promise and limitations in recent studies. In comparison to normal tissues, LncRNAs are differentially expressed in ECs, and their dysregulation has been associated to tumor grade, lymph node metastasis, depth of myometrial invasion, FIGO stage and patient survival. Oncogenic lncRNAs (CCAT2, BANCR, NEAT1, MALAT1, LINP1, SRA and LSINCT5) and tumor suppressor lncRNAs (GAS5, MEG3, OIP5-AS1, FER1L4, and LINC00672) have been identified as downstream effectors or upstream modulators of important signaling pathways driving EC metastasis, including the PTEN/PI3K/AKT/mTOR, RAS/RAF/MEK/ERK, WNT/β-catenin, and p53 signaling pathways. Short non-coding RNAs called miRNAs also effect expression of genes at the post-transcriptional level. Multiple studies have shown that miRNAs play a critical role in the regulation of EC. We present a review of ncRNA expression patterns, prognostic significance, biological function and roles in the tumor microenvironment in EC cells in EC associated pathways. We also discuss how ncRNAs can be used as biomarkers for EC diagnosis and as potential therapeutic targets for different EC subtypes based on their ncRNA signature.

Keywords

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