Long non-coding RNAs in esophageal cancer: molecular mechanisms, functions, and potential applications

Abstract

Esophageal cancer (EC) is the sixth leading cause of cancer-related death worldwide. The lack of early diagnostic biomarkers and effective prognostic indicators for metastasis and recurrence has resulted in the poor prognosis of EC. In addition, the underlying molecular mechanisms of EC development have yet to be elucidated. Accumulating evidence has demonstrated that lncRNAs play a vital role in the pathological progression of EC. LncRNAs may regulate gene expression through the recruitment of histone-modifying complexes to the chromatin and through interactions with RNAs or proteins. Recent evidence has demonstrated that the dysregulation of lncRNAs plays important roles in the proliferation, metastasis, invasion, angiogenesis, apoptosis, chemoradiotherapy resistance, and stemness of EC, which suggests potential clinical implications. In this review, we highlight the emerging roles and regulatory mechanisms of lncRNAs in the context of EC and discuss their potential clinical applications as diagnostic and prognostic biomarkers.

Keywords: Application; Biomarker; Esophageal cancer; Long non-coding RNA; Mechanism.

Fig. 1

The molecular mechanisms underlying esophageal cancer-related lncRNAs rely on interactions with cellular macromolecules. (a) LncRNAs localize to the chromatin. LncRNAs recruit chromatin modification complexes to the promoter region of chromatin and the results in (1) histone methylation or acetylation, (2) DNA methylation; lncRNAs recruit chromatin modification complexes to specific loci of chromatin and modulate gene expression through (3) chromatin modification. (b) LncRNAs interacts with RNA. (4) LncRNAs interacts with pre-mRNA, affect alternative splicing and help to produce mature mRNAs; (5) lncRNAs act as miRNA sponges or compete for endogenous RNAs (ceRNAs) and compete for miRNAs to inactivate these small regulatory RNAs, followed by relief of the repression of the target gene. (c) LncRNAs interact with proteins.( 6) LncRNAs regulates protein dephosphorylation and activity; (7) lncRNAs regulate protein localization; (8) lncRNAs modulate protein–protein interactions; (9) lncRNAs directly localize within cellular compartments to serve as structural components