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

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.

SUBMITTER: Gao Y

PROVIDER: S-EPMC7327794 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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

Gao Yue Y Wang Jun-Wei JW Ren Jia-Yi JY Guo Mian M Guo Cheng-Wang CW Ning Shang-Wei SW Yu Shan S

World journal of gastroenterology 20200601 24

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 ...[more]

PMID: 32655264

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Project description:BackgroundGastric cancer (GC) is a globally prevalent cancer, ranking fifth for incidence and fourth for mortality worldwide. The N6-methyladenosine (m6A) related long noncoding RNAs (lncRNAs) were widely investigated in recent studies. Nevertheless, the underlying prognostic implication and tumor immune mechanism of m6A-related lncRNA in GC remain unknown.MethodsWe systematically assessed the m6A modification expression of 407 GC clinical samples based on 23 m6A regulators and comprehensively associated these genes with lncRNAs. Then, we constructed a m6A-related lncRNA prognostic signature (m6A-LPS) to evaluate both status and prognosis of the disease. Immune-related mechanisms were explored via dissecting tumor-infiltrating cells as well as applying tumor immune dysfunction and the exclusion algorithm. Furthermore, we validated the latent regulative mechanism of m6A-related lncRNA in GC cell lines.ResultsThe m6A-LPS containing nine hub lncRNAs was built, which possessed a superior capability to predict the outcomes of GC patients. Meanwhile, we found an intimate correlation between the m6A-LPS and tumor infiltrating cells, and that the low-risk group had a higher expression of immune checkpoints and responsed more to immunotherapy than the high-risk group. Clinically, these crucial lncRNAs expression levels were verified in ten pairs of GC samples. In in vitro experiments, the abilities of migration and proliferation were significantly enhanced via downregulating the lncRNA AC026691.1. Both migrative and proliferative capabilities of tumor cells were significantly enhanced via downregulating the lncRNA AC026691.1. in vitro.ConclusionsCollectively, the m6A-LPS could provide a novel prediction insight into the prognosis of GC patients and serve as an independent clinical factor for GC. These m6A-related lncRNAs might remodel the tumor microenvironment and affect the anti-cancer ability of immune checkpoint blockers. Importantly, lncRNA AC026691.1 could inhibit both migration and proliferation of GC by means of FTO regulation.

Dataset Information

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

Publications

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

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