Circ-PTPDC1 promotes the Progression of Gastric Cancer through Sponging Mir-139-3p by Regulating ELK1 and Functions as a Prognostic Biomarker.
Ontology highlight
ABSTRACT:
SUBMITTER: Li Z
PROVIDER: S-EPMC8579456 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Abnormal expression of circular RNA (circRNA) is closely related to the occurrence and development of many cancers. By screening the expression of circRNA, we identified a novel circRNA termed as has_circ_0023326 in laryngeal squamous cell carcinoma (LSCC). We verified the expression of circPPFIA1 and found that it was upregulated in LSCC tissues compared to the adjacent normal tissues. Functional studies were carried out to detect the effect of circPPFIA1 expression on the phenotype of LSCC cells. These results suggest that circPPFIA1 knockdown can suppress the proliferation, migration, and invasion of LSCC cells, while circPPFIA1 overexpression can promote these processes. Mechanistically, miR-340-3p was predicted to be the target miRNA sponged by circPPFIA1 as confirmed through the luciferase assay and rescue experiments. In addition, miR-340-3p was found to target ELK1 and inhibit its expression. Taken together, circPPFIA1 promotes the progression of LSCC via the miR-340-3p/ELK1 signaling axis, which may serve as a novel prognostic or therapeutic target for LSCC.
| S-EPMC8806628 | biostudies-literature
Project description:Lung adenocarcinoma (LUAD) is the most common lung cancer with high incidence. The prognosis of LUAD is poor due to its aggressive behavior. Long non‑coding RNAs (lncRNAs) have been reported as a key modulator on LUAD progression. Therefore, the present study aimed to clarify the molecular mechanism of lncRNAs in LUAD development. The expression of lncRNA RP11‑805J14.5 (RP11‑805J14.5) in LUAD tissues and cells was quantified based on the data in The Cancer Genome Atlas (TCGA). Cell viability was determined using Cell Counting Kit‑8 method. Apoptotic cells were sorted and determined by flow cytometry. Cell migration and invasion abilities were detected by the Transwell assay. Luciferase reporter experiment and RNA pull‑down assay were utilized to determine the interactions between RP11‑805J14.5, microRNA (miR)‑34b‑3p, miR‑139‑5p, and cyclin D2 (CCND2). A xenograft tumor was established to determine tumor growth in vivo. RP11‑805J14.5 was highly expressed in LUAD and associated with poor survival of LUAD patients. Knockdown of RP11‑805J14.5 suppressed LUAD cell growth, invasion, migration and tumor growth, indicating that RP11‑805J14.5 is an important regulator of LUAD. Our study demonstrated that the regulation of RP11‑805J14.5 on LUAD was mediated by CCND2 whose expression was regulated by sponging miR‑34b‑3p and miR‑139‑5p. The expression of RP11‑805J14.5 was increased in LUAD, and the knockdown of RP11‑805J14.5 expression suppressed LUAD cell growth, invasion and migration by downregulating CCND2 by sponging miR‑34b‑3p and miR‑139‑5p, indicating that RP11‑805J14.5 could be a prospective target for LUAD therapy.
| S-EPMC9350987 | biostudies-literature
Project description:IntroductionHepatocellular carcinoma (HCC) is one most common cancer types among gastrointestinal cancer over the world, while its underlying mechanisms remain unclear. CircRNA has been revealed to participate in multiple biological functions and contribute to various diseases' progression.MethodsBioinformatic analysis of the differently expressed circRNAs in the HCC tissues, then verified by real-time quantitative PCR (RT-qPCR) assay. We found that circ-0003006 was upregulated in the HCC tissues, the cell fractionation assay and RNA fluorescence in situ hybridization (FISH) were performed to confirm the cell location of circ-0003006. shRNA silence assay was used to knock down the expression of circ-0003006 in the HCC cells.ResultsCell account kit 8 (CCK-8) and transwell assay were revealed that circ-0003006 knockdown inhibited the proliferation and metastasis in HCC cells. The target miR‑542‑3p and target gene HIF-1A were predicted by bioinformatics analysis, then verified through biotinylated RNA pull-down and dual-luciferase reporter assays. The mechanism, circ-0003006, probably acted as a sponge of miR‑542‑3p and regulated HIF-1A levels in hepatocellular carcinoma cells. Moreover, HIF-1A overexpression abolished the effect of circ-0003006 inhibition on the progression of hepatocellular carcinoma cells. The subcutaneous tumor formation experiment indicated that circ-0003006 knockdown inhibited the HCC cell growth in vivo.ConclusionCirc-0003006 was demonstrated to promote HCC progression in vitro and in vivo by sponging miR‑542‑3p to release the inhibition on HIF-1A.
| S-EPMC8520847 | biostudies-literature
Project description:BackgroundPrevious studies have shown that long noncoding RNA (lncRNA) LINC00483 was aberrantly expressed in human cancers, including gastric cancer. However, the regulatory mechanism of this lncRNA in gastric cancer remains largely unknown. The present study aimed to investigate the effect of LINC00483 on gastric cancer development and explore the potential regulatory network of LINC00483/microRNA (miR)-490-3p/mitogen-activated protein kinase 1 (MAPK1).MethodsThirty patients with gastric cancer were recruited for tissues collection. The expression levels of LINC00483, miR-490-3p and MAPK1 were detected by quantitative real-time polymerase chain reaction or western blot. Cell viability, apoptosis, migration and invasion were determined by MTT, flow cytometry, transwell assays and western blot, respectively. The target association between miR-490-3p and LINC00483 or MAPK1 was confirmed by luciferase reporter assay. Xenograft model was established to assess the function of LINC00483 in vivo.ResultsLINC00483 and MAPK1 levels were increased in gastric cancer tissues and cells. Knockdown of LINC00483 or MAPK1 inhibited cells viability, migration and invasion but promoted apoptosis in gastric cancer cells. Moreover, MAPK1 overexpression attenuated the effect of LINC00483 knockdown on gastric cancer development. LINC00483 could increase MAPK1 expression by competitively sponging miR-490-3p. miR-490-3p overexpression suppressed gastric cancer development, which was abated by introduction of LINC00483. Besides, inhibition of LINC00483 decreased xenograft tumor growth by regulating miR-490-3p/MAPK1 axis.ConclusionKnockdown of LINC00483 inhibited gastric cancer development in vitro and in vivo by increasing miR-490-3p and decreasing MAPK1, elucidating a novel mechanism for understanding the development of gastric cancer.
| S-EPMC7158027 | biostudies-literature
Project description:Ossification of the posterior longitudinal ligament (OPLL) is a disorder with multiple pathogenic mechanisms and leads to different degrees of neurological symptoms. Recent studies have revealed that non-coding RNA (ncRNA), including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), could influence the development of OPLL. Nevertheless, the molecular mechanisms linking circular RNAs (circRNAs) and the progression of OPLL is still unknown. The current research explored the expression profiles of OPLL-related circRNAs by microarray analysis, and applied qRT-PCR to validate the results. Subsequently, we confirmed the upregulation of hsa_circ_0007292 in OPLL cells by qRT-PCR and validated the circular characteristic of hsa_circ_0007292 by Sanger sequencing. Fluorescence in situ hybridization (FISH) unveiled that hsa_circ_0007292 was predominantly located in the cytoplasm. Functionally, gain-of-function and loss-of-function experiments showed that hsa_circ_0007292 promoted the osteogenic differentiation of OPLL cells. Mechanistically, the interaction of hsa_circ_0007292 and miR-508-3p was predicted and validated by bioinformatics analysis, dual-luciferase reporter assays, and Ago2 RNA immunoprecipitation (RIP). Similarly, we validated the correlation between miR-508-3p and SATB2. Furthermore, rescue experiments were performed to prove that hsa_circ_0007292 acted as a sponge for miR-508-3p, and SATB2 was revealed to be the target gene of miR-508-3p. In conclusion, our research shows that hsa_circ_0007292 regulates OPLL progression by the miR-508-3p/SATB2 pathway. Our results indicate that hsa_circ_0007292 can be used as a promising therapeutic target for patients with OPLL.
| S-EPMC8436939 | biostudies-literature
Project description:Background: Circular RNAs (circRNAs) are a new class of RNAs that play a significant role in regulating gene expression and biological function. However, the expression profile and function of circRNAs in gastric cancer (GC) remain mostly uncertain. In the present study, we researched the expression profile of circRNAs in human GC tissues and explored the role of circCACTIN (hsa_circ_0092303). Methods: Circular RNA microarray assays were performed to detect circular RNA expression profiles of GC and circCACTIN was identified for further investigation. Quantitative real-time PCR was used to detect the expression of circCACTIN, miR-331-3p and TGFBR1 in GC specimens and cell lines. CircCACTIN was stably silenced and overexpressed in GC cells, and cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), as well as tumorigenesis in nude mice were performed to assess the effect of circCACTIN on GC. Results: CircCACTIN expression was obviously up-regulated in GC tissues and cell lines. Knockdown of circCACTIN inhibited GC cells proliferation, migration, invasion and EMT. Enforced-expression of circCACTIN promoted GC cells migration, invasion and EMT, but had no effect on GC cells proliferation. Moreover, in vivo experiments, circCACTIN up-regulation promoted GC tumor growth and EMT, and circCACTIN down-regulation inhibited GC tumor growth and EMT. Binding interactions were detected between circCACTIN and miR-331-3p, and between miR-331-3p and TGFBR1 by Dual-luciferase reporter assays. Mechanistically, we demonstrated that circCACTIN promoted gastric cancer progression by sponging miRNA-331-3p and regulating TGFBR1 mRNA expression. Conclusion: The circCACTIN/miR-331-3p/TGFBR1 axis affected the proliferation, migration, invasion and EMT of GC through the mechanism of competing endogenous RNAs (ceRNA). Furthermore, our results identified circCACTIN as a novel oncogenic circRNA in GC.
| S-EPMC6535790 | biostudies-literature
Project description:Background:The aim of the present study was to investigate the effect of over-expressing circular RNA (circ_0003645) on cell functions and its molecular mechanism in breast cancer. Methods:The expression profile of circ_0003645, breast cancer cell lines, and the transcription levels of circular RNA, miRNA and HMGB1 gene were detected by qRT-PCR. Flow cytometry analysis was manipulated to evaluate cancer cell proliferation and cell apoptosis. The correlation between miR-139p-3p and circular_0003645 or HMGB1 was predicted by GEO, and TCGA was confirmed using the dual-luciferase reporter assay. Results:Circ_0003645 expression was conspicuously increased in both the breast cancer tissues and cell lines. Circ_0003645 knockdown inhibited cell proliferation and induced the apoptosis of breast cancer cells in vitro and in vivo. By sponging miR-139-3p, circ_0003645 promoted the breast cancer cells progression and positively regulated HMGB1 gene. Conclusion:Circ_0003645 functions as a ceRNA for miR-139-3p, which could upregulate HMGB1 and further promote cell proliferation in breast cancer.
| S-EPMC7568624 | biostudies-literature
Project description:Objective:To explore the regulatory effects of circZNF609 on proliferative and migratory capacities of gastric cancer (GC) and its underlying mechanism. Methods:Expression level of circZNF609, CDK6 and miR-483-3p in GC tissues and cells were detected qRT-PCR verification. CCK-8 and transwell assay were conducted the cell viability and migratory capacities of GC cells. Dual luciferase assay was enrolled to confirm the interaction among circZNF609, CDK6 and miR-483-3p. Western blot was used to detect the protein level of CDK6. Results:Expression levels of circZNF609 were higher in GC patients by qRT-PCR.GC patients with higher expression of circZNF609 were expected to have a higher TNM stage and lower 5-year survival than those with lower expression. ROC curves showed a well diagnostic value of circZNF609 in GC. Treatment of RNase R in GC cells downregulated the expression of ZNF609, whereas circZNF609 expression did not change. Furthermore, cytoplasmic expression of circZNF609 was higher than those of nuclear expression. Besides, biological experiments indicated that overexpression of circZNF609 promoted the proliferative and migratory capacities of GC cells. To demonstrate the underlying mechanism of circZNF609, we found that circZNF609 bound to miR-483-3p, which presented a lower expression in GC tissues than that of paracancerous tissues. Both circZNF609 and miR-483-3p could bind to Ago2, suggesting that circZNF609 may act as a sponge of miR-483-3p. In addition, the effect of overexpressed circZNF609 on cellular behaviors of GC cells were partly reversed by overexpression of miR-483-3p. Bioinformatics suggested that CDK6 has a potential binding site with miR-483-3p. The expression of CDK6 markedly increased in GC tissues and cells, which was negatively correlated with miR-483-3p expression. Dual-luciferase reporter gene results indicated that miR-483-3p could bind to the 3'-UTR of CDK6. Moreover, miR-483-3p downregulated CDK6 at both mRNA and protein levels. Overexpression of miR-483-3p inhibited proliferative and migratory capacities of GC cells, which were reversed by CDK6 overexpression. Conclusion:In summary, the expression of circZNF609 is upregulated in GC. CircZNF609 can be used as the sponge of miR-483-3p to regulate the expression level of CDK6, thus participating in the progression of GC by regulating the proliferative and migratory capacities of GC cells.
| S-EPMC6783112 | biostudies-literature
Project description:Background:Accumulating data indicated that circRNA plays important roles in regulating many biological processes of the tumor, the present study is designated for exploring roles of the circ-ZEB1.33-miR-200a-3p-CDK6 regulating axis in human hepatocellular carcinoma (HCC). Methods:The regulation axis as predicted by using online tool circNet, the expression and correlation of circ-ZEB1.33-miR-200a-3p-CDK6 was verified in human HCC. The diagnostic value of both tumor and serum circ-ZEB1.33 was estimated by using clinical samples. The roles of circ-ZEB1.33-miR-200a-3p-CDK6 in regulating cell cycle were explored by using in vitro studies. Results:Overexpression of circ-ZEB1.33 and CDK6, downregulation of miR-200a-3p were detected in human HCC tissues, negative correlation between circ-ZEB1.33 and miR-200a-3p, positive correlation between circ-ZEB1.33 and CDK6 were confirmed in human HCC tissues. Tissue and serum circ-ZEB1.33 were related to different TMN stages and prognosis in HCC patients. RNA pull-down assay implied that circ-ZEB1.33 could decrease miR-200a-3p by sponging miR-200a-3p, and the luciferase reporter assay indicated that miR-200a-3p could downregulate CDK6 transcription by targeting its 3'UTR. The in vitro assays indicated that circ-ZEB1.33 could promote the proliferation of HCC cells by increasing the percentage of S phase regulated by CDK6/Rb. Conclusion:Proliferation promotion roles of the circ-ZEB1.33-miR-200a-3p-CDK6 regulating axis are existed and verified in human HCC, both tumor and serum circ-ZEB1.33 can serve as an indicator for the prognosis of HCC patients.
| S-EPMC6090603 | biostudies-literature
Project description:BACKGROUND:Non-coding RNAs (ncRNAs) have been reported to participate in tumor progression by regulating gene expression. Previous studies showed that protein phosphatase Mg2+/Mn2+ dependent 1F (PPM1F) acts a dual role in cancer growth and metastasis. But, the underlying mechanisms by which ncRNAs regulate PPM1F expression in hepatocellular carcinoma (HCC) are poorly understood. METHODS:The association between PPM1F or miR-490-3p expression and clinicopathological features and prognosis in patients with HCC was analyzed by TCGA RNA-sequencing data. CircSLC3A2 was identified to bind with miR-490-3p by bioinformatic analysis, and the binding sites between miR-490-3p and PPM1F or circSLC3A2 were confirmed by dual luciferase report and RNA immunoprecipitation (RIP) assays. The localization and clinical significance of miR-490-3p and circSLC3A2 in patients with HCC were investigated by fluorescence in situ hybridization (FISH). MTT, Agar, and Transwell assays were conducted to evaluate the effects of miR-490-3p or circSLC3A2 on cell proliferation and invasive potential. RESULTS:The expression of PPM1F or miR-490-3p was associated with poor survival and tumor recurrence, and acted as an independent prognostic factor in patients with HCC. Re-expression of miR-490-3p inhibited HCC cell proliferation and invasion by targeting PPM1F, but its inhibitor reversed these effects. Moreover, circSLC3A2, predominantly localized in the cytoplasm, exhibited an oncogenic role by sponging miR-490-3p and regulating PPM1F expression, and harbored a positive correlation with poor survival in patients with HCC. CONCLUSION:CircSLC3A2 acts as an oncogenic factor in HCC by sponging miR-490-3p and regulating PPM1F expression.
| S-EPMC6260990 | biostudies-literature