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Long non-coding RNAs involved in metastasis of gastric cancer.

ABSTRACT: Gastric cancer (GC) is one of the most frequently diagnosed malignant diseases. The molecular mechanisms of metastasis remain unclear. Recently, studies have shown that long non-coding RNAs (lncRNAs) play critical roles in metastasis. Therefore, deeper understanding of this mechanism could provide potential diagnostic tools and therapeutic targets for metastatic GC. This review focuses on dysregulated lncRNAs in GC metastases. Due to the identification of multiple diverse mechanisms involved in GC metastasis, we classified them into seven categories, including lncRNAs related to epithelial-mesenchymal transition, regulation of degradation of extracellular matrix, angiopoiesis, vasculogenic mimicry, and immunologic escape. As the TNM stage is pivotal for evaluating the severity and prognosis of GC patients, we summarize the lncRNAs relevant to lymphatic metastasis, distant metastasis and TNM classification. This review summarizes the lncRNAs related to metastasis, which may provide insight into the mechanisms, and provide potential markers for prognostic prediction and monitoring the relapse of GC.

SUBMITTER: Lin MT

PROVIDER: S-EPMC6127659 | biostudies-other | 2018 Sep

REPOSITORIES: biostudies-other

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Long non-coding RNAs involved in metastasis of gastric cancer.

Lin Meng-Ting MT Song Hao-Jun HJ Ding Xiao-Yun XY

World journal of gastroenterology 20180901 33

Gastric cancer (GC) is one of the most frequently diagnosed malignant diseases. The molecular mechanisms of metastasis remain unclear. Recently, studies have shown that long non-coding RNAs (lncRNAs) play critical roles in metastasis. Therefore, deeper understanding of this mechanism could provide potential diagnostic tools and therapeutic targets for metastatic GC. This review focuses on dysregulated lncRNAs in GC metastases. Due to the identification of multiple diverse mechanisms involved in ...[more]

PMID: 30197478

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Project description:Long non‑coding RNAs (lncRNAs) play critical roles in the development and progression of cancers. The present study aimed to identify novel lncRNAs and associated microRNAs (miRNAs or miRs) and mRNAs in gastric cancer. Differentially expressed lncRNAs (DElncRNAs) and differentially expressed mRNAs (DEmRNAs) of 6 paired gastric cancer and normal tissues were identified using microarray. The DEmiRNAs between gastric cancer and the normal control tissues were identified using miRNA‑seq data from Cancer Genome Atlas. Common DElncRNAs from the Cancer RNA‑Seq Nexus database and circlncRNAnet database were analyzed. A DElncRNAs‑DEmiRNAs‑DEmRNAs network was constructed by target prediction. Functional enrichment analysis was employed to predict the function of DEmRNAs in the network. The correlation between the expression of DElncRNAS and DEmRNAs in the network was analyzed. The expression levels of several genes were validated by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). A total of 1,297 DElncRNAs, 2,037 DEmRNAs and 171 DEmiRNAs were identified. Among the 4 lncRNAs common to the 3 datasets, prostate androgen‑regulated transcript 1 (PART1) was selected for further analysis. The analysis identified 5 DEmiRNAs and 13 DEmRNAs in the PART1‑mediated ceRNA network. The DEmRNAs in the ceRNA network were markedly enriched in cancer‑related biological processes (response to hypoxia, positive regulation of angiogenesis and positive regulation of endothelial cell proliferation) and pathways (cGMP‑PKG signaling pathway, cAMP signaling pathway and proteoglycans in cancer). Out of the 13 DEmRNAs, 11 were positively associated with PART1. The downregulation of PART1, myosin light chain 9 (MYL9), potassium calcium‑activated channel subfamily M alpha 1 (KCNMA1), cholinergic receptor muscarinic 1 (CHRM1), solute carrier family 25 member 4 (SLC25A4) and ATPase Na+/K+ transporting subunit alpha 2 (ATP1A2) expression levels in gastric cancer was validated by RT‑qPCR. On the whole, the current study identified a novel lncRNA and associated miRNAs and mRNAs that are involved in the pathogenesis of gastric cancer that may serve as potential therapeutic targets for the treatment of gastric cancer.

Project description:Abnormal regulation of long non-coding RNAs (lncRNAs) appears to be a primary feature of numerous types of human cancer. However, the association between the dysregulation of lncRNAs and functional alterations in gastric cancer (GC) remains unclear. In previous studies, we applied microarray and bioinformatics analyses to screen for key lncRNAs from the tumor tissues and matched adjacent non-tumor tissues of 10 patients with GC. There were seven key lncRNAs demonstrated to be significantly different between carcinoma tissues and adjacent non-tumor tissues. In the present study, the expression of these seven selected lncRNAs were validated in 82 patients with GC to further investigate the association between lncRNAs and GC clinical characterization. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results demonstrated that RP5-919F19, MCPH1 antisense RNA 1 (CTD-2541M15) and urothelial carcinoma-associated 1 (UCA1) exhibited consistent upregulation in cancer compared with adjacent non-tumor tissues, whereas AP000459, LOC101928316, tumor suppressor candidate 8 (LINC01071) and maternally expressed 3 (MEG3) showed consistent downregulation. The results from the microarray and RT-qPCR experiments achieved 100% agreement. A correlation analysis indicated that RP5-919F19, LOC101928316 and MEG3 were significantly associated with tumor differentiation degree, RP5-919F19, UCA1 and MEG3 were significantly associated with lymph node metastasis, and RP5-919F19, CTD-2541M15 and UCA1 were significantly associated with tumor-node-metastasis stage (P<0.05). In addition, it was identified that the differential expression of LINC01071 and LOC101928316 significantly correlated with the age and gender of the GC patients, respectively (P<0.05). The results suggest that the lncRNAs RP5-919F19, LOC101928316, CTD-2541M15, UCA1 and MEG3 are closely associated with the invasion and metastasis of GC, which reveals these indicators as potential specificity biomarkers for the diagnosis, prognosis and classification of GC. Thus, these lncRNAs merit further study as novel candidate biomarkers for the clinical diagnosis of GC and as potential targets for therapy.

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Long non-coding RNAs involved in metastasis of gastric cancer.

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Long non-coding RNAs involved in metastasis of gastric cancer.

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