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

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. 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. 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. 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.

Xu Y ，Zhang G ，Zou C ，Zhang H ，Gong Z ，Wang W ，Ma G ，Jiang P ，Zhang W ... -  《-》

lncRNA SNHG4 enhanced gastric cancer progression by modulating miR-409-3p/CREB1 axis.

Gastric cancer (GC) is a globally common cancer characterized by high incidence and mortality worldwide. Advances in the molecular understanding of GC provide promising targets for GC diagnosis and therapy. Long non-coding RNAs (lncRNAs) and their downstream regulators are regarded to be implicated in the progression of multiple types of malignancies. Studies have shown that the lncRNA small nucleolar RNA host gene 4 (SNHG4) serves as a tumor promoter in various malignancies, while its function in GC has yet to be characterized. Therefore, our study aimed to explore the role and underlying mechanism of SNHG4 in GC. We used qRT-PCR to analyze SNHG4 expression in GC tissues and cells. Kaplan-Meier analysis was used to assess the correlation between SNHG4 expression and the survival rate of GC patients. Cellular function experiments such as CCK-8, BrdU, colony formation, flow cytometry analysis, and transwell were performed to explore the effects of SNHG4 on GC cell proliferation, apoptosis, cell cycle, migration, and invasion. We also established xenograft mouse models to explore the effect of SNHG4 on GC tumor growth. Mechanically, dual luciferase reporter assay was used to verify the interaction between SNHG4 and miR-409-3p and between miR-409-3p and cAMP responsive element binding protein 1 (CREB1). The results indicated that SNHG4 was overexpressed in GC tissues and cell lines, and was linked with poor survival rate of GC patients. SNHG4 promoted GC cell proliferation, migration, and invasion while inhibiting cell apoptosis and cell cycle arrest in vitro. The in vivo experiment indicated that SNHG4 facilitated GC tumor growth. Furthermore, SNHG4 was demonstrated to bind to miR-409-3p. Moreover, CREB1 was directly targeted by miR-409-3p. Rescue assays demonstrated that miR-409-3p deficiency reversed the suppressive impact of SNHG4 knockdown on GC cell malignancy. Additionally, miR-409-3p was also revealed to inhibit GC cell proliferation, migration, and invasion by targeting CREB1. In conclusion, we verified that the SNHG4 promoted GC growth and metastasis by binding to miR-409-3p to upregulate CREB1, which may deepen the understanding of the underlying mechanism in GC development.

Cheng Z ，Hua Y ，Cao Y ，Qin J ... -  《-》

The PVT1-214/miR-671-5p/SLC45A4 signaling axis regulates cell proliferation in human gastric cancer.

Long non-coding RNA PVT1 (lncRNA PVT1) serves as a carcinogenic regulatory factor in several cancers; however, the expression and function of its transcriptional isomer PVT1-214 in gastric cancer (GC) are poorly understood. PVT1-214 and miR-671-5p levels in GC cells and tissues were analyzed through quantitative real-time polymerase chain reaction (qRT-PCR). Western blotting (WB) was used to detect Homo sapiens solute carrier family 45 member 4 (SLC45A4) expression in GC cells. Thereafter, the relationship between PVT1-214 and miR-671-5p was evaluated through dual-luciferase reporter assays and RNA immunoprecipitation (RIP) analysis. Additionally, the biological activities of PVT1-214, miR-671-5p and SLC45A4 in GC cells were analyzed through Cell Counting Kit-8 (CCK-8), 5-ethyl-20-deoxyuridine (EdU), colony formation and Transwell assays. The effect of PVT1-214 on GC was studied in vivo via a nude mouse tumor xenograft model. PVT1-214 overexpression in GC cells and tissues was positively related to tumor size, malignancy grade, lymphatic metastasis and clinical stage. PVT1-214 knockdown suppressed cell growth, invasion and migration in vitro, whereas PVT1-214 overexpression promoted tumor proliferation in vivo. In addition, PVT1-214 positively regulates SLC45A4 expression through its competitive endogenous RNA (ceRNA) activity against miR-671-5p. SLC45A4 expression was positively related to PVT1-214 expression. PVT1-214 competes with endogenous RNA (ceRNA) by binding to miR-671-5p. When miR-671-5p is inhibited, SLC45A4 is released from the complementary binding complex, thereby increasing SLC45A4 protein levels in GC cells. The present work revealed the candidate ceRNA regulatory pathway by which PVT1-214 regulates SLC45A4 expression in GC cells, which is achieved through competitive binding to endogenous miR-671-5p. The results of this study can shed novel light on new molecular targets for treating GC.

Yan W ，Wang H ，Zhao Y ，Zhang W ，Li Y ... -  《World Journal of Surgical Oncology》

LINC00240 promotes gastric cancer cell proliferation, migration and EMT via the miR-124-3p / DNMT3B axis.

Gastric cancer (GC) remains one of prevalent causes of cancer-related deaths worldwide. Long noncoding RNA is related to various cancers. Our study was conducted to explore the biological effects of LINC00240 on the tumorigenesis of GC and uncover its possible mechanisms. LINC00240 expression was determined in GC cell lines and samples through quantitative Real-time Polymerase Chain Reaction (qRT-PCR). The functional effects of LINC00240 were validated using in vitro and in vivo assays. Targets were assessed by AGO2-dependent RNA immunoprecipitation assay and dual-luciferase report assays. Our findings suggested higher LINC00240 expression in GC tissues and cells. Through downregulating LINC00240, cell proliferation, invasion and migration were retarded in vitro, and tumorigenesis of GC cells was notably suppressed in vivo. Further research showed that LINC00240 was a cytoplasmic lncRNA that shared miRNA response elements of microRNA (miR)-124-3p with DNMT3B, thus forming a LINC00240/miR-124-3p/DNMT3B axis explaining the functions of LINC00240. In a word, our study reveals that LINC00240 promotes GC tumorigenesis via a LINC00240/miR-124-3p/DNMT3B axis as an oncogene. These findings objectivise that LINC00240 may be a potential diagnostic biomarker for GC. SIGNIFICANCE OF THE STUDY: Gastric cancer (GC) is the fifth most common cancer and the third leading cause of cancer-related death across the world. Then we analysed lncRNA microarray of GC and selected LINC00240 as the study object. Therefore, the potential molecular mechanism as well as physiological function of LINC00240 in GC was discussed. Then we reveal that LINC00240 acts as an oncogene in GC progression via the miR-99a-5p/IGF1R axis. This study is the first to demonstrate the roles of LINC00240 in GC.

Li Y ，Yan J ，Wang Y ，Wang C ，Zhang C ，Li G ... -  《-》

Circular RNA circPFKP suppress gastric cancer progression through targeting miR-346/CAMD3 axis.

Studies have demonstrated that circular RNAs (circRNAs) exert an important regulatory function in the pathogenesis of various tumors. However, their role in gastric cancer (GC) is still not completely understood. In our study, the differentially expressed circRNAs in GC tissues and matched adjacent normal tissues were analyzed by utilizing gene chips GSE93541, GSE89143, and GSE78092. The expression of has_circ_0006608 (circPFKP), miR-346, and CAMD3 was analyzed through quantitative real-time polymerase chain reaction (qRT-PCR). The CCK-8 assay and Transwell assay were employed to detect the effect of circPFKP on the proliferation, migration, and invasion of gastric cancer cells. The mice xenograft assay was used to assess the function of circPFKP in vivo. The targeting relationship between circPFKP, miR-346, and CAMD3 was predicted by bioinformatics analysis and confirmed by the dual-luciferase reporter assay and RNA pull-down assay. Our results screened and verified that circPFKP was down-regulated in gastric cancer tissues and cells. Overexpression of circPFKP in GC cells can inhibit cell proliferation, migration, invasion, and tumor growth in vivo. Additionally, circPFKP has been shown to act as a sponge for miR-346 to modulate the expression of CAMD3. Finally, we demonstrated that overexpression of CAMD3 or miR-346 inhibitor significantly reversed the effects of si-circPFKP on the proliferation, migration, and invasion of gastric cancer cells. In conclusion, this study provided that circPFKP inhibits the progression of GC via the miR-346/CAMD3 axis, this may provide a noval biomarker for the diagnosis and treatment of GC.

Song X ，Zhang G ，Niu J ，Liu H ，Li C ，Ning W ，Zhou L ... -  《-》