Current advances in the functional role of long non-coding RNAs in the oncogenesis and metastasis of esophageal squamous cell carcinoma: a narrative review

Abstract

Background and objective: Esophageal squamous cell carcinoma (ESCC) is a significant global health challenge characterized by increasing incidence and generally poor prognosis. The search for novel biomarkers and therapeutic targets is crucial for improving patient outcomes. Long non-coding RNAs (lncRNAs) have emerged as key players in cancer research. The objective of this review is to explore the role of lncRNAs in ESCC, identifying their potential as diagnostic indicators and therapeutic targets. This review aims to provide a strategic overview of lncRNAs in ESCC, emphasizing their significance in disease progression and clinical implications for patient management.

Methods: To identify published lncRNAs biomarkers for diagnosing or predicting the course of ESCC, we performed a literature search in the PubMed and PubMed Central databases, utilizing specific search terms.

Key content and findings: This paper reviews the critical role of lncRNAs in ESCC and explores their functions in tumourigenesis and metastasis. Differential expression of lncRNAs is closely related to tumour aggressiveness and patient prognosis. Up-regulated lncRNAs usually promote tumour growth and predict poor prognosis, whereas down-regulated lncRNAs exert oncogenic effects and are associated with better clinical outcomes. In addition, lncRNAs play a role in the tumour microenvironment, influencing immune escape and treatment resistance. Despite the promising role of lncRNAs in ESCC therapy, their heterogeneity and complex regulatory mechanisms remain a challenge for clinical application. Future studies should focus on revealing their specific mechanisms and developing precise targeted therapeutic strategies to improve the outcome of ESCC patients. The dysregulation of lncRNAs correlates with tumor aggression and patient prognosis, underscoring a need for targeted therapies. Understanding lncRNAs mechanisms could pave the way for personalized medicine, enhancing early detection, and treatment efficacy in ESCC.

Conclusions: LncRNAs represent a novel frontier in ESCC research, with significant implications for patient management. Future studies should focus on deciphering lncRNAs functions within ESCC's molecular landscape to facilitate the development of effective targeted therapies. The integration of lncRNAs research into clinical practice is poised to transform ESCC treatment strategies, offering hope for improved patient outcomes.

Keywords: Long non-coding RNAs (lncRNAs); biomarkers; differential expression; esophageal squamous cell carcinoma (ESCC); signaling pathways.

Figure 1

The block diagram of differential expression in esophageal squamous cell carcinoma. EAC, esophageal adenocarcinoma; ESCC, esophageal squamous cell carcinoma; lncRNA, long non-coding RNA.

Figure 2

The regulatory function of oncogenic and tumor suppressor long non-coding RNAs in PI3K/AKT/mTOR signaling pathway in the pathogenesis of esophageal cancer. EMT, epithelial-mesenchymal transition; ESCC, esophageal squamous cell carcinoma; JAB1 Protein, c-Jun activation domain-binding protein 1; LAMC2, Laminin γ2 chain; miR-133b, microRNA-133b; miR-877-3p, microRNA-877-3p; P, phosphorylation; PI3K/AKT/mTOR, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin; PMEP, pemetrexed; SOX2, Sex-determining region Y box 2; TWIST, Twist-related protein.

Figure 3

The regulatory function of oncogenic and tumor suppressor long non-coding RNAs in Wnt/β-catenin signaling pathway in the pathogenesis of esophageal cancer. EMT, epithelial-mesenchymal transition; ESCC, esophageal squamous cell carcinoma; EXoN1, exonuclease 1; FOXP4, forkhead box p4; ICAM-1, intercellular adhesion molecule-1; MMP2, matrix metalloproteinase 2; MLL2, mixed lineage leukemia 2; P, phosphorylation; SNAI1, Snail family zinc finger 1; VEGF-A, vascular endothelial growth factor A; WIF-1, WNT inhibitory factor 1; WISP1, WNT1 inducible signaling pathway protein 1; ZEB2, Zinc finger e-box binding homeobox 2.

Figure 4

The regulatory function of oncogenic and tumor suppressor long non-coding RNAs in p53 signaling pathway in the pathogenesis of esophageal cancer. CDK2, cyclin dependent kinase 2; CDK416, cyclin dependent kinase 416; CPSF4, cleavage and polyadenylation specific factor 4; ELAVL1, ELAV like RNA binding protein 1; ESCC, esophageal squamous cell carcinoma; MDM2, murine double minute 2; miR-139-3P, microRNA-139-3p; miR-466, microRNA-466; mRNA, messenger ribonucleic acid; P, phosphorylation; P53, tumor protein p53; PTEN, phosphatase and tensin homolog; YTHDF2, YTH N6-methyladenosine RNA binding protein 2.

Figure 5

The regulatory function of oncogenic and tumor suppressor long non-coding RNAs in MAPK signaling pathway in the pathogenesis of esophageal cancer. 3UTR, 3' untranslated region; EMT, epithelial-mesenchymal transition; ERK1/2, extracellular-regulated kinase 1/2; ESCC, esophageal squamous cell carcinoma; IGF2BP1, insulin-like growth factor 2 mRNA binding protein 1; MAPK, mitogen-activated protein kinase; MKK6, mitogen-activated protein kinase kinase 6; m6A, N6-methyladenosine; miR-328-5P, microRNA-328-5p; P, phosphorylation.

Figure 6

The regulatory function of oncogenic and tumor suppressor long non-coding RNAs in JAK/STAT signaling pathway in the pathogenesis of esophageal cancer. EMT, epithelial-mesenchymal transition; ESCC, esophageal squamous cell carcinoma; JAK/STAT, Janus kinase/signal transducer and activator of transcription; miR-124, microRNA-124; P, phosphorylation; PD-L1, programmed cell death-ligand 1.

Figure 7

The regulatory function of oncogenic and tumor suppressor long non-coding RNAs in MiR-Axis signaling pathway in the pathogenesis of esophageal cancer. ACACA, acetyl-coenzyme A carboxylase alpha; EMT, epithelial-mesenchymal transition; ESCC, esophageal squamous cell carcinoma; FASN, Fatty acid synthase; FOXP2, forkhead box p2; HIF1AN, Hypoxia inducible factor 1 subunit alpha inhibitor; IGF1R, insulin-like growth factor 1 receptor; P, phosphorylation; PBX3, Pre-B cell leukemia homeobox 3; SCD1, Stearoyl-coA desaturase 1; SPHK1, sphingosine kinase 1; VEGFA, vascular endothelial growth factor A.

Figure 8

The regulatory function of oncogenic and tumor suppressor long non-coding RNAs in TGF-β1 signaling pathway in the pathogenesis of esophageal cancer. EMT, epithelial-mesenchymal transition; ESCC, esophageal squamous cell carcinoma; NCK1-AS1, NCK 1 antisense RNA 1; P, phosphorylation; TGF-β1, transforming growth factor beta 1.

Figure 9

The regulatory function of oncogenic and tumor suppressor long non-coding RNAs in GSK-3β/snail signaling pathway in the pathogenesis of esophageal cancer. EMT, epithelial-mesenchymal transition; ESCC, esophageal squamous cell carcinoma; GSK-3β, glycogen synthase kinase-3 beta; MEG3, maternally expressed gene 3; P, phosphorylation.