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 ... -  《-》

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 ... -  《-》

Has_circ_ASH1L acts as a sponge for miR-1254 to promote the malignant progression of cervical cancer by targeting CD36.

Cervical cancer (CC) is a prevalent gynecological malignancy. Increasing evidence suggests that circular RNAs (circRNAs) play a pivotal role in the pathogenesis of CC. However, the regulatory function of circ_ASH1L in CC remains elusive. In this study, we aim to elucidate the precise role and underlying mechanism of circ_ASH1L in the malignant progression of CC. The human CC dataset GSE102686 was extracted from the Gene Expression Omnibus (GEO) database for the analysis of differentially expressed circRNAs. Target gene prediction softwares were utilized to predict the binding of miRNAs to circ_ASH1L sponge. The expression level of circ_ASH1L in CC tissues and cells was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The characteristics of circ_ASH1L were determined by RNase R digestion, actinomycin D, and nucleo-plasmic separation assays. The effects of circ_ASH1L, miR-1254, and CD36 gain-and-loss on the malignant progression of CC were investigated using Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, wound scratch, transwell, and Western blot assay. The effect of circ_ASH1L on tumorigenicity of CC cells in vivo was evaluated in nude mice through tumor xenograft assay. The targeted regulatory relationship between circ_ASH1L/miR-1254 as well as miR-1254/CD36 was validated by dual-luciferase reporter assay. We screened the differentially expressed circ_ASH1L from the GEO dataset GSE102686 and confirmed its circular structure. Furthermore, we observed a significant upregulation of circ_ASH1L in both CC tissues and cells. Overexpression of circ_ASH1L promotes proliferation, invasion, and migration of CC cells while inhibiting cell apoptosis. However, silencing circ_ASH1L showed opposite results and inhibited tumorigenicity of CC cells in nude mice. Furthermore, we have identified circ_ASH1L as a miR-1254 sponge in CC cells. Notably, our in vitro experiments demonstrated that exogenously modulating the expression of miR-1254 effectively counteracted the impact of circ_ASH1L on the malignant phenotypic characteristics of CC cells. Similarly, modulation of CD36 expression efficiently counteracted the effect of miR-1254 on the malignant biological behavior of CC cells. In conclusion, circ_ASH1L promoted the malignant progression of CC via upregulating CD36 expression through sponging miR-1254.

Zhang J ，Zhang Y ，Li X ，Bao Y ，Yang J ... -  《-》

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 ... -  《-》

Circular RNA contributes to gastric cancer by targeting Wnt family member 2B as a competing endogenous RNA.

As a non-coding RNA molecule, circular RNAs (circRNAs) have significant specificity, and existing data suggest a close relationship between them and the prognosis of patients with gastric cancer (GC). However, this mechanism has no evidence yet. This article explores the functions of hsa_circRNA_102415 in the malignant behavior and potential downstream signaling of GC cells. The chosen approach is loss of signal and functional gain. To investigate and analyze the relationship between hsa_circRNA_102415 and GC and explore its specific role. Results provide reference for other researchers to develop targeted treatment plans. The gene expression omnibus (GEO) database can be used to obtain the microarray dataset GSE83521. Data were analyzed using the GEO2R tool to identify differences in circRNAs between normal and GC samples. Quantitative real-time polymerase chain reaction was used to detect differentially expressed genes in GC tissue samples and adjacent cancer tissue samples. GC cells were transfected with small interfering-hsa_circRNA_104415 and plasmid DNA (pcDNA)-hsa_ircRNA_102415. Multiple detection methods, such as Transwell and cell counting kit 8, were used to evaluate cellular physiological activities, including cell invasion and proliferation. The relationship between Wnt family members 2B, microRNA (miR)-4529-5p, etc., including argonaute 2-RNA immunoprecipitation and luciferase reporter genes was analyzed. Rescue experiments were conducted to analyze and explore the relationship between the malignant behavior of GC cells and hsa_circRNA_102415. GEO2R analysis confirmed that hsa_circRNA_102415 had significantly higher expression levels in disease tissues. hsa_circRNA_102415 and miR-4529-5p showed a negative correlation in disease cells, suggesting that hsa_circRNA_102415 upregulated WNT2B expression in GC cells as a competing endogenous RNA for miR-4529-5p. miR-4529-5p mimic or small interfering-WNT2B reversed the effects of pcDNA-hsa_circRNA_102415 or miR-4529-5p inhibitor on cell malignant functions. miR-4529-5p was used to successfully activate the potential of WNT2B, clarify the role of hsa_circRNA_102415 in GC cells, and provide reference for other researchers to develop targeted treatment plans.

Bai W ，Guo ZL ，Guo JH ，Li F ，Bu P ，Liu J ... -  《-》