Non-coding RNAs in gastric cancer

Xie, Shanshan; Chang, Yongxia; Jin, Hao; Yang, Feng; Xu, Yanjun; Yan, Xin; Lin, Aifu; Shu, Qiang; Zhou, Tian

doi:10.1016/j.canlet.2020.06.022

Cited by 50 publications

(33 citation statements)

References 201 publications

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“…The role of ncRNAs, represented by microRNAs, in tumors, especially in gastric cancer, has been extensively studied in recent years (9)(10)(11)(12)(13). MicroRNAs can promote the degradation of RNA by targeting the 3′-UTR of the corresponding RNA, which can be regulated at the post-transcriptional level (14).…”

Section: Discussionmentioning

confidence: 99%

The RNA-Binding Protein DDX18 Promotes Gastric Cancer by Affecting the Maturation of MicroRNA-21

Zhang

et al. 2021

Front. Oncol.

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ObjectivesThe noncoding RNAs (ncRNAs) play important roles in gastric cancer. Most studies have focused on the functions and influence of ncRNAs, but seldom on their maturation. DEAD box genes are a family of RNA-binding proteins that may influence the development of ncRNAs, which attracted our attention. By combining a small sample for high-throughput gene microarray screening with large samples of The Cancer Genome Atlas (TCGA) data and our cohort, we aimed to find some gastric cancer-related genes. We evaluated the clinical significance and prognostic value of candidate gene DDX18, which is overexpressed in gastric cancer tissues. To provide a theoretical basis for the development of new therapeutic targets for the treatment of gastric cancer, we investigated its effect on the malignant biological behavior of gastric cancer in vitro and in vivo, and also discuss its mechanism of action.Methods(i) The differential profiling of mRNA expression in five pairs of gastric cancer and adjacent normal tissues was studied by Arraystar Human mRNA Microarray. By combining this with TCGA data and our cohort, we finally filtered out DDX18, which was upregulated in gastric cancer tissues, for further investigation. (ii) The protein expression of DDX18 was detected by immunohistochemistry staining. Then the relationship between the DDX18 expression level and the clinicopathological data and prognosis was analyzed. (iii) A CCK-8 assay and colony formation assay were used to evaluate the effect of DDX18 on cell growth and proliferation in vitro. A transwell assay was also performed to examine the migration and invasion of gastric cancer cells. Cell apoptosis was analyzed by using a fluorescein isothiocyanate–annexin V/propidium iodide double-staining assay. To identify the role of DDX18 in the tumorigenic ability of gastric cancer cells in vivo, we also established a subcutaneous gastric cancer xenograft model. Coimmunoprecipitation, small RNAseq, and western blotting were performed to explore the mechanism of action of DDX18 in gastric cancer. A patient-derived xenograft (PDX) model was used to confirm the effect of DDX18 in gastric cancer tissues.Result(i) DDX18 was upregulated in gastric cancer tumor tissues from a TCGA database and our cohort. The expression of DDX18 was also closely related to tumor volume, Borrmann classification, degree of tumor differentiation, cancer embolus, lymph node metastasis, and TNM stage. (ii) DDX18 could promote cell proliferation, migration, and invasion and inhibit cell apoptosis in vivo and in vitro. (iii) DDX18 could promote the maturation of microRNA-21 through direct interaction with Drosha, decreasing PTEN, which could upregulate the AKT signaling pathway. (iv) The PDX model showed that DDX18 could promote the proliferation of gastric cancer tissues by means of the PTEN–AKT signaling pathway.Conclusions(i) DDX18 can be treated as a molecular marker to assess the prognosis of patients with gastric cancer. (ii) DDX18 could be a potential therapeutic target in gastric cancer.

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Section: Discussionmentioning

confidence: 99%

The RNA-Binding Protein DDX18 Promotes Gastric Cancer by Affecting the Maturation of MicroRNA-21

Zhang

et al. 2021

Front. Oncol.

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“…Moreover, the correlation of altered ncRNAs with GC progression has been wellacknowledged. 25 In our study, we conducted tissue and cell experiments to test whether SNHG22 and miR-361-3p orchestrated GC cell biological function. Our findings highlighted that downregulation of SNHG22 hampered GC cell proliferation, migration and invasion and HUVEC angiogenesis but accelerated GC cell apoptosis and cell cycle arrest by disrupting HMGA1-activated Wnt/ β-catenin pathway via miR-361-3p.…”

Section: Discussionmentioning

confidence: 99%

<p>Long Noncoding RNA SNHG22 Induces Cell Migration, Invasion, and Angiogenesis of Gastric Cancer Cells via microRNA-361-3p/HMGA1/Wnt/β-Catenin Axis</p>

Cui¹,

Zhang²,

Chen³

et al. 2020

CMAR

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Background The correlation between long non-coding RNAs (lncRNAs) and gastric cancer (GC) has been indicated. As a newly found lncRNA, small nucleolar RNA host gene 22 (SNHG22) functions as an oncogene in ovarian carcinoma and breast cancer. However, its action has not been explored in GC. Herein, the purpose of the current research was to examine the influence of SNHG22 on GC development. Methods RT-qPCR was used to identify SNHG22 and microRNA-361-3p (miR-361-3p) in GC tissues and cells. Functional assays were implemented to measure changes on biological activities of GC cells under different transfections. Besides, after human umbilical vein endothelial cells (HUVECs) were co-cultured with supernatant of transfected GC cells, angiogenesis was assessed by tube formation assay in vitro. HMGA1 and β-catenin expression were determined. Finally, mechanistic assays, including RNA pull-down assay and dual-luciferase reporter assay, were employed to assess relationships among SNHG22, miR-361-3p, and HMGA1. Results SNHG22 and HMGA1 were highly expressed but miR-361-3p was poorly expressed in GC tissues. Mechanistically, SNHG22 bound to miR-361-3p, and miR-361-3p targeted HMGA1 to disrupt the Wnt/β-catenin pathway. Following SNHG22 or HMGA1 silencing or miR-361-3p upregulation, we observed a decline of proliferation, migration, and invasion of GC cells and HUVEC angiogenesis but acceleration of GC cell apoptosis and cell cycle arrest. Conclusion Collectively, SNHG22 silencing possessed tumor-suppressing potentials in GC development via Wnt/β-catenin pathway by binding to miR-361-3p and downregulating HMGA1, highlighting a new promising road for GC treatment development.

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“…Long non-coding RNAs (lncRNAs) lack the ability to encode protein, but are capable of regulating cellular physiology through complex epigenetic mechanism [ 3 ]. Many functionally important lncRNAs have been detected and studied in recent years, and have been shown to suppress or promote GC invasion, growth, and metastasis [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

LncRNA HOXA-AS3 promotes gastric cancer progression by regulating miR-29a-3p/LTβR and activating NF-κB signaling

Feng

Zhu

et al. 2021

Cancer Cell Int

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Background Gastric cancer (GC) is among the most common and deadliest cancers globally. Many long non-coding RNAs (lncRNAs) are key regulators of GC pathogenesis. This study aimed to define the role of HOXA-AS3 in this oncogenic context. Methods Levels of HOXA-AS3 expression in GC were quantified via qPCR. The effects of HOXA-AS3 knockdown on GC cells function were evaluated in vitro using colony formation assays, wound healing assays and transwell assays. Subcutaneous xenograft and tail vein injection tumor model systems were generated in nude mice to assess the effects of this lncRNA in vivo. The localization of HOXA-AS3 within cells was confirmed by subcellular fractionation, and predicted microRNA (miRNA) targets of this lncRNA and its ability to modulate downstream NF-κB signaling in GC cells were evaluated via luciferase-reporter assays, immunofluorescent staining, and western blotting. Results GC cells and tissues exhibited significant HOXA-AS3 upregulation (P < 0.05), and the levels of this lncRNA were found to be correlated with tumor size, lymph node status, invasion depth, and Helicobacter pylori infection status. Knocking down HOXA-AS3 disrupted GC cell proliferation, migration, and invasion in vitro and tumor metastasis in vivo. At a mechanistic level, we found that HOXA-AS3 was able to sequester miR-29a-3p, thereby regulating the expression of LTβR and modulating NF-κB signaling in GC. Conclusion HOXA-AS3/miR-29a-3p/LTβR/NF-κB regulatory axis contributes to the progression of GC, thereby offering novel target for the prognosis and treatment of GC.

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Non-coding RNAs in gastric cancer

Cited by 50 publications

References 201 publications

The RNA-Binding Protein DDX18 Promotes Gastric Cancer by Affecting the Maturation of MicroRNA-21

The RNA-Binding Protein DDX18 Promotes Gastric Cancer by Affecting the Maturation of MicroRNA-21

<p>Long Noncoding RNA SNHG22 Induces Cell Migration, Invasion, and Angiogenesis of Gastric Cancer Cells via microRNA-361-3p/HMGA1/Wnt/β-Catenin Axis</p>

LncRNA HOXA-AS3 promotes gastric cancer progression by regulating miR-29a-3p/LTβR and activating NF-κB signaling

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