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Review
. 2020 Jun 28;26(24):3401-3412.
doi: 10.3748/wjg.v26.i24.3401.

Long noncoding RNAs in gastric cancer: From molecular dissection to clinical application

Yue Gao  1 , Jun-Wei Wang  2 , Jia-Yi Ren  1 , Mian Guo  3 , Cheng-Wang Guo  4 , Shang-Wei Ning  1 , Shan Yu  5
Affiliations
Review

Long noncoding RNAs in gastric cancer: From molecular dissection to clinical application

Yue Gao et al. World J Gastroenterol. .

Abstract

Long noncoding RNAs (lncRNAs) are important regulators of cell processes that are usually dysregulated in gastric cancer (GC). Based on their high specificity and ease of detection in tissues and body fluids, increasing attention has spurred the study of the roles of lncRNAs in GC patients. Thus, it is necessary to elucidate the molecular mechanisms and further explore the clinical applications of lncRNAs in GC. In this review, we summarize current knowledge to examine dysregulated lncRNAs in GC and their underlying molecular mechanisms and activities in GC, which involve microRNA sponging, mRNA stability, genetic variants, alternative splicing, transcription factor binding, and epigenetic modification. More significantly, the potential of lncRNAs as prognostic, circulating, and drug-resistant biomarkers for GC is also described. This review highlights the method of dissecting molecular mechanisms to explore the clinical application of lncRNAs in GC. Overall, this review offers assistance in using lncRNAs as novel candidates for molecular mechanisms and for the identification of revolutionary biomarkers for GC.

Keywords: Biomarkers; Drug resistance; Gastric cancer; Long noncoding RNAs; Molecular mechanism; Therapeutic target.

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Conflict of interest statement

Conflict-of-interest statement: The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Molecular mechanism of long noncoding RNAs in gastric cancer. A: MicroRNA (miRNA) sponge. H19 and GAPLINC, acting as molecular sponges, bind to miR-675 and miR-211-3p, thus increasing the expression of their target genes RUNX1 and Cd44; B: mRNA stability. Target transcripts are stabilized or decayed when long noncoding RNA (lncRNA) binds to mRNA; C: Genetic variants. Genetic variants located at lncRNAs influence the expression of lncRNA; D: Alternative splicing. LINC00477 generates three transcripts based on alternative splicing; E: Transcription factor binding. Transcription factor directly interacts with the lncRNA PVT1 and regulates its expression; F: Epigenetic modification; G: DNA methylation. DNA methylation sites located at or near lncRNA regulate lncRNA expression; H: Histone modification. H3K27me results in suppression or gain of transcriptional activity.
Figure 2
Figure 2
Potential clinical application of long noncoding RNAs as biomarkers in gastric cancer. A: Long noncoding RNAs (lncRNAs) with dysregulated expression or variants can act as prognostic biomarkers for gastric cancer (GC) patients; B: Dysregulated lncRNAs identified from body fluids can be used to detect GC; C: Selected dysregulated lncRNAs are associated with drug resistance in GC patients, animal models, and cell lines. lncRNA: Long noncoding RNA.
See this image and copyright information in PMC

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