The Human RNA Surveillance Factor UPF1 Modulates Gastric Cancer Progression by Targeting Long Non-Coding RNA MALAT1

Background/Aims: Recent evidence has shown that some long non-coding RNAs (lncRNAs) play important roles in various biological processes. However, the regulatory mechanism of lncRNA in gastric cancer (GC) remains unclear. Methods: We reannotated the GC gene expression profile into a lncRNA-mRNA biphasic profile and integrated the microRNA target data to construct a global GC triple network. A further clustering and random walk with restart analyses was performed on the triple network from the level of topology analyses. Quantitative real-time PCR was used to determine expression of lncRNA RP11-363E7.4. Kaplan-Meier analyses was performed to evaluate the prognostic value of lncRNA RP11-363E7.4. Results: We constructed a gastric cancer lncRNA-miRNA-mRNA network (GCLMN) including six lncRNAs, 332 mRNAs, and 3,707 edges. For the shared lncRNA RP11-363E7.4, the interacting gene and microRNA functional enrichment studies implied that lncRNA RP11-363E7.4 might function as a new regulator in GC. The expression of lncRNA RP11-363E7.4 was downregulated compared with that of paracarcinoma tissues in five GC samples. High expression of lncRNA RP11-363E7.4 was found to be correlated to better overall survival (OS) for GC patients. Conclusions: This study focused on GC lncRNA-miRNA-mRNA regulatory networks, and found that lncRNA RP11-363E7.4 was a new GC risk lncRNA, which might provide novel insight into a better understanding of the pathogenesis of GC.

Section: Discussionmentioning

confidence: 99%

A Novel LncRNA-miRNA-mRNA Triple Network Identifies LncRNA RP11-363E7.4 as An Important Regulator of miRNA and Gene Expression in Gastric Cancer

Wang

Zhao

et al. 2018

“…Functioned as oncogenes or tumor suppressors, lncRNAs participate in several vital steps of GC tumorigenesis and progression. Some lncRNAs including HOTAIR, HULC, LINC00152, MALAT1, MALAT2, H19, SNHG6, GHET1 and GACAT3 have been demonstrated to act as oncogenes, while other lncRNAs such as LEIGC, GAS5 and FER1L4 have been classified as tumor suppressors [9][10][11][12]. Mechanistically, lncRNAs may act as chromatin remodeler, transcriptional modulator, splicing regulator, posttranscriptional processor, enhancer, molecular decoys for miRNAs, or as a guide for protein-protein, protein-DNA and protein-RNA interaction [4,5,13,14].…”

Section: Introductionmentioning

confidence: 99%

LncRNA MT1JP Suppresses Gastric Cancer Cell Proliferation and Migration Through MT1JP/MiR-214-3p/RUNX3 Axis

Xü

Zhang

Zou

et al. 2018

Background/Aims: Emerging evidence points towards an important role of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of gastric cancer (GC). MT1JP has recently been reported to be differentially expressed and act as a tumor suppressor in different tumors, with its mechanisms not fully understood in GC. Methods: RT-qPCR was used to detect the expression of MT1JP, miR-214-3p and RUNX3 in tumor tissues and cell lines of GC. The CCK-8 assay, colony formation, Transwell assay and wound healing assay were used to evaluate the proliferation, invasion and migration of GC cells, respectively. Bioinformatics analysis and luciferase reporter assay were performed to disclose the interaction between MT1JP, miR-214-3p and RUNX3. Western blot and immunofluorescence were applied to assess the downstream signaling of RUNX3. Results: MT1JP was found downregulated in GC tissues and cells. Low expression of MT1JP was significantly correlated with advanced TNM stage and lymphatic metastasis. The expression of plasma MT1JP was also found decreased in GC patients compared to healthy controls, with an area under the ROC curve (AUC) of 0.649 for diagnosis of GC. Gain-and loss-of-function of MT1JP revealed that MT1JP functioned as a ceRNA for miR-214-3p to facilitate RUNX3 expression and then upregulated p21 and Bim levels suppressing GC cell proliferation, invasion and migration, and promoting apoptosis. Furthermore, MT1JP overexpression suppressed tumor growth and inhibited the expression of miR-214-3p and proliferation antigen Ki-67, but increased the expression of RUNX3, p21 and Bim in vivo. Conclusions: Our results suggest a potential ceRNA regulatory network involving MT1JP regulates RUNX3 expression by competitively binding endogenous miR-214-3p in tumorigenesis and progression of GC. This mechanism may contribute to a better understanding of GC pathogenesis and provide potential therapeutic strategy for GC.

“…EGFR plays an important role in cell migration, proliferation, cell cycle regulation and other physiological processes [7]. EGFR is up-regulated in various cancers including gastric cancer [12,13], and is recognized as oncogenic driver in tumorigenesis. LncRNA EGFR antisense RNA 1 (EGFR-AS1) is a 2.8-kb transcript that transcribes in the antisense strand of EGFR [17,18].…”

Section: Introductionmentioning

confidence: 99%

Long Noncoding RNA EGFR-AS1 Promotes Cell Proliferation by Increasing EGFR mRNA Stability in Gastric Cancer

Qian

Peng

et al. 2018

Background/Aims: LncRNA EGFR-AS1 is an antisense transcript of EGFR, which plays a key role in gastric cancer progression. This study was aimed to explore the effects of lncRNA EGFR-AS1 on GC and the underling mechanisms. Methods: The silencing of EGFR-AS1 expression was performed by using EGFR-AS1 shRNA lentivirus in MGC803 and SGC-7901 GC cell. The levels of lncRNA EGFR-AS1 and EGFR were detected by qPCR and western blot. Cell proliferation was assessed by CCK-8, EdU, and colony formation assays. The EGFR mRNA stability was explored by using RNA synthesis inhibitor α-amanitin. Results: In our study, EGFR-AS1 significantly up-regulated in GC tissues and correlated with tumor size. And the expression of EGFR-AS1 positively correlated with EGFR in tissues. Moreover, knock-down of EGFR-AS1 inhibited the proliferation of GC cells via suppressing EGFR-dependent PI3K/AKT pathway in vitro and in vivo. Mechanismly, depletion of EGFR-AS1 was found to decrease EGFR expression by reduction of EGFR mRNA stability. Conclusion: Our findings suggested that EGFR-AS1 might have an oncogenic effect on GC and serve as a potential target of GC.