RacGAP1 promotes the malignant progression of cervical cancer by regulating AP-1 via miR-192 and p-JNK.
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ABSTRACT:
SUBMITTER: Zhang T
PROVIDER: S-EPMC9279451 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe long-term prognosis of HCC (hepatocellular carcinoma) with metastasis remains extremely poor. CircRNAs are promising as critical biological markers in identifying disease mechanisms and developing new effective treatments. However, the role of the aberrant expression of circRNAs in HCC progression remains largely unknown.MethodsCircKIF5B location was investigated by RNA fluorescence in situ hybridization (RNA-FISH). For circRNA determination, RNase R treatment and Real-Time Quantitative RT-PCR (qRT-PCR) were performed. Transwell chamber assays examined the chemotactic migration and invasion of liver cancer cells.ResultsThis study identified the circRNA circKIF5B originating from exons 1, 2, and 3 of the KIF5B gene. Importantly, we found that circKIF5B circRNA, rather than KIF5B linear mRNA, was notably upregulated in liver cancer cell lines and tissues. Moreover, we found that silencing circKIF5B markedly reduced the proliferation, invasion, and metastasis of liver cancer cells by sponging the miR-192 family, thus decreasing the expression of X-linked inhibitor of apoptosis (XIAP).ConclusionOur data demonstrate that circKIF5B can regulate XIAP expression by sponging miR-192 and miR-215 competing for the ceRNA mechanism, indicating that circKIF5B may act as an essential upstream regulator and providing mechanistic evidence to support the view that circKIF5B/miR-192s/XIAP is a promising therapeutic target for treating liver cancer.
| S-EPMC9281474 | biostudies-literature
Project description:The aim of the present study was to explore the effects of LINC00649 on the proliferation, migration and invasion of bladder cancer (BC) and identify possible mechanisms. Through TCGA database analysis of LINC00649 expression in bladder cancer and the association of LINC00649 with the BC patient prognosis, RT‑qPCR was employed for detecting LINC00649 expression in 60 clinical tissue specimens and cell lines of bladder cancer. The lentivirus stable transfection or small interfering RNA was used to increase or decrease the LINC00649 expression level in T24 and UM‑UC‑3 cells. CCK8 and clone formation assay were utilized to observe the effects of LINC00649 on the proliferation and colony formation of BC cells. Transwell experiment was performed to detect the effects of LINC00649 on the migration and invasion of bladder cancer. Bioinformatics database was used to identify the possible downstream targets of LINC00649 while RT‑qPCR, western blot analysis and dual luciferase reporter gene experiments were carried out to verify the possible molecular mechanism. The TCGA database analysis revealed a significantly high expression of LINC00649 in bladder cancer and an association of LINC00649 expression with overall survival rate of BC patients. As shown by RT‑qPCR detection, LINC00649 expression was notably upregulated in BC tissues and BC cell lines. In addition, statistical analyses unveiled that highly expressed LINC00649 was clearly associated with poor overall survival of bladder cancer. Based on the in vitro cell experiment, upregulated LINC00649 considerately enhanced the proliferation, migration and invasion of BC cells, as opposed to those in T24 and UM‑UC‑3 cells by suppressing LINC00649. Mechanically, LINC00649 may promote the malignant progression of bladder cancer by regulating miR‑15a‑5p to promote the HMGA1 expression axis. Overall, LINC00649 upregulates HMGA1 expression by binding to miR‑15a‑5p to enhance the proliferation, migration and invasion of BC cells. Thus, LINC00649 is a potential biomarker and therapeutic target for bladder cancer.
| S-EPMC7876990 | biostudies-literature
Project description:The purpose of this article is to explore the function and mechanism of HOXD-AS1 in cholangiocarcinoma. TCGA, StarBase and JASPAR were applied to predict the differential expression and molecular mechanism. The qRT-PCR was conducted to detect molecular expression. The effect of HOXD-AS1 on tumor proliferation, metastasis and stemness was measured through corresponding experiments. ChIP, luciferase reporter and RIP assays were implemented to explore the regulatory mechanism of HOXD-AS1 in CCA. In this study, HOXD-AS1 expression was significantly upregulated in CCA tissues and cells compared with control groups, respectively. Increased HOXD-AS1 was markedly correlated with lymph node invasion, advanced TNM stage and poor survival of CCA patients. Moreover, HOXD-AS1 was confirmed to be an unfavorable independent prognostic factor for CCA patients. Functionally, gain- and loss-of-function experiments demonstrated that HOXD-AS1 facilitated tumor proliferation, migration, invasion, EMT, stemness and drug resistance in vitro and in vivo. For the mechanism, transcription factor SP1-induced HOXD-AS1 upregulated oncogene MYCN through competitively binding to miR-520c-3p. Furthermore, HOXD-AS1-induced malignant phenotypes were rescued by interfering miR-520c-3p and MYCN, respectively. SP1/HOXD-AS1/miR-520c-3p/MYCN plays a vital role in initiation and progression of CCA, and HOXD-AS1 is expected to be an efficient biomarker and therapeutic target.
| S-EPMC7485728 | biostudies-literature
Project description:Circular RNAs (circRNAs) are a group of non-coding RNAs that have an essential function in the development and progression of various cancers. The expression pattern and function of circRNA in cervical squamous cell carcinoma (CESC) are not fully understood. In the present study, we aimed to investigate the expression profiles and regulation mechanism of circRNA circ_POLA2 in CESC. Circ_POLA2 was highly expressed in CESC tissues and positively correlated with poor prognosis in CESC patients. Knockdown of circ_POLA2 using shRNA inhibited cervical cancer cell proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, circ_POLA2 could sponge endogenous microRNA-326 (miR-326) and inhibit its expression. Furthermore, miR-326 negatively regulated G protein subunit beta 1 (GNB1) by targeting its 3'-UTR. Intriguingly, we found that GNB1 was overexpressed and associated with poor prognosis in CESC patients. Overexpression of GNB1 could antagonize the inhibitory effect of miR-326 on cervical cancer cell proliferation, migration, and invasion. In addition, we demonstrated that circ_POLA2/miR-326/GNB1 axis regulated ERK signaling. In conclusion, circ_POLA2 promotes cervical squamous cell carcinoma development and progression via regulating the miR-326/GNB1 axis, which might serve as a novel therapeutic target for CESC patients.
| S-EPMC7381119 | biostudies-literature
Project description:BackgroundSome recent studies have reported the role of circular RNAs (circRNAs) in modulating the tumorigenesis of human malignancies. Nevertheless, the expression characteristics, biological functions, and regulatory mechanism of circ_0000189 in glioma are unclear.MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) was utilized to detect the expression levels of circ_0000189, miR-192-5p, and ZEB2 mRNA in glioma tissues and cells. The association between the expression of circ_0000189 and the clinicopathological indicators and the features of magnetic resonance imaging (MRI) images of glioma patients were analyzed. Western blot was utilized to evaluate ZEB2 expression and epithelial-mesenchymal transition (EMT-)-related proteins (E-cadherin, N-cadherin, as well as Vimentin) in glioma cells. Cell proliferation was assessed employing cell counting kit-8 (CCK-8) and EdU experiments. Flow cytometry was used to detect the apoptotic rate of the cells. Cell migration and invasion were accessed employing Transwell assay. Moreover, dual luciferase reporter gene assay and RNA immunoprecipitation assay were employed to investigate the targeting relationship between miR-192-5p and circ_0000189, miR-192-5p, and ZEB2. Subcutaneous tumorigenesis experiment and lung metastasis experiment in nude mice were conducted to verify the regulatory function of circ_0000189 on the proliferation and metastasis of glioma cells in vivo.Resultscirc_0000189 was markedly overexpressed in glioma tissues and cell lines. Its high expression was associated with poor clinical pathological indicators and adverse MRI signs. Gain-of-function experiments and loss-of-function experiments confirmed that circ_0000189 overexpression facilitated the proliferation and migration, as well as invasion of glioma cells, and suppressed apoptosis, and facilitated epithelial-mesenchymal transition (EMT) process. Compared to the control group, knocking down circ_0000189 suppressed the malignant phenotypes of glioma cells both in vivo and in vitro. Working as a competitive endogenous RNA, circ_0000189 directly targeted miR-192-5p, and repressed its expression, and circ_0000189 positively modulated ZEB2 expression indirectly via repressing miR-192-5p.Conclusioncirc_0000189 facilitates the progression of glioma by modulating miR-192-5p/ZEB2 axis.
| S-EPMC9526621 | biostudies-literature
Project description:Objective: Previous studies have demonstrated that circular RNAs (circRNAs) play vital roles in pathological process of various diseases, including tumors. This study aimed at exploring the role and mechanism of circRNA RNA ZNF609 (circ-ZNF609) in the occurrence and development of glioma. Materials and methods: Real-time quantitative PCR (qRT-PCR) was applied to measure the expression of circ-ZNF609, miRNA-1224-3p (miR-1224-3p) and Polo-like kinase 1 (PLK1) in glioma tissues and cell lines. Furthermore, the association between circ-ZNF609 and clinical features of glioma was analyzed. CCK8 assay, EdU assay and Transwell assay were conducted to detect the effect of circ-ZNF609, miR-1224-3p and PLK1 on proliferation, migration and invasion in glioma cells. Then, we investigated the underlying mechanism of circ-ZNF609 by bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation (RIP), qRT-PCR and western blotting assay. Results: Circ-ZNF609 was confirmed prominently upregulated in glioma. Inhibition of circ-ZNF609 could obviously suppress glioma cell proliferation, migration and invasion, while overexpression of circ-ZNF609 promoted glioma growth and metastasis. In vivo, xenotransplanted tumor model also showed that overexpression of circ-ZNF609 could promote in vivo glioma growth. Mechanistically, circ-ZNF609 could promote PLK1 expression via binding to miR-1224-3p, circ-ZNF609/miR-1224-3p/PLK1 was shown responsible for circ-ZNF609 promoting glioma growth and metastasis. Conclusion: Together, our results revealed that circ-ZNF609 elevates glioma growth and metastasis via enforcing PLK1 expression by competitively binding miR-1224-3p, suggesting that circ-ZNF609 might be an underlying therapeutic target for glioma.
| S-EPMC8100806 | biostudies-literature
Project description:Background:Long non-coding RAN five prime to Xist (LncRNA FTX) has been revealed to be a cancer-related lncRNA and implicated in the progression of colorectal cancer (CRC). Besides, miR-192-5p (miR-192) or eukaryotic initiation factor 5A2 (EIF5A2) also was identified to link with the tumorigenesis of CRC. Here, we further explored the function of FTX and the regulatory relationship among FTX, miR-192 and EIF5A2 in CRC progression. Methods:Levels of FTX, miR-192-5p and EIF5A2 were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot, respectively. Cell proliferation, apoptosis, migration and invasion were analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry or transwell assay, respectively. The interaction between miR-192-5p and FTX or EIF5A2 was confirmed by dual-luciferase reporter and pull-down assay. Murine xenograft model was established using LoVo cells transfected with sh-FTX. Results:FTX was up-regulated in CRC tissues and cell lines, knockdown of FTX inhibited CRC cell proliferation, migration and invasion in vitro as well as suppressed CRC tumor growth in vivo. FTX was confirmed to directly bind to miR-192-5p and negatively regulated miR-192-5p expression in CRC cells. Besides that overexpressed FTX positively modulated EIF5A2, a direct target of miR-192-5p, via miR-192-5p in CRC cells. Importantly, the inhibitory activities on CRC progression mediated by FTX deletion were reversed miR-192-5p down-regulation or EIF5A2 up-regulation. Conclusion:LncRNA FTX functioned as an oncogene to contribute to CRC progression by regulating miR-192-5p/EIF5A2 axis, providing a novel insight into the pathogenesis of CRC and a promising therapeutic target for CRC treatment.
| S-EPMC7127817 | biostudies-literature
Project description:Background: Epigenetic regulation by promoter methylation-mediated silencing of cancer-related microRNAs plays vital roles in tumorigenesis. MiR-192-5p promotes tumor progression in various human cancers with conflicting biological effects. However, its expression levels and biological functions in endometrial carcinoma (EC) have not been reported. Methods: The methylation status of miR-192-5p in tissue samples and cell lines, was examined using bisulfite sequencing PCR. miR-192-5p expression was also measured. EC cell lines transfected with specifically designed vectors overexpressing miR-192-5p, its target gene ALX1 or both, were constructed. Tumorigenicity of these cell lines were examined by in vitro and in vivo experiments. Dual-luciferase reporter assay were employed to verify the target of miR-192-5p. Results: The promoter region of miR-192-5p gene was highly methylated and its expression significantly repressed in EC samples. Moreover, a higher level of promoter methylation as well as a lower expression of miR-192-5p, was significantly associated with advanced Federation of Gynecology and Obstetrics stage and shorter disease-free survival in patients with curatively resected EC. Functional studies demonstrated that miR-192-5p overexpression inhibited in vitro tumor progression, in vivo tumorigenicity and the expression of several oncoproteins that was highly related to epithelial-to-mesenchymal transition. ALX1 was verified as a direct target of miR-192-5p and demonstrated to mediate the tumor-suppressive function of miR-192-5p. Conclusion: miR-192-5p is a tumor suppressor miRNA that is epigenetically silenced by promoter methylation and may serve as a potential prognostic biomarker in EC.
| S-EPMC8176185 | biostudies-literature
Project description:BackgroundLong non-coding RNAs (lncRNAs) have recently been found to be vital regulators of various cancers, including colorectal cancer (CRC). It has been previously reported that the dysregulated expression of lncRNA Five prime to Xist (FTX) is involved in carcinogenesis. However, the role of lncRNA FTX in the progression of CRC is still unclear.MethodsFluorescence in situ hybridization (FISH) was used to detect the expression of lncRNA FTX and miR-214-5p in CRC tissues. Cell Counting Kit-8 assay, transwell assay, wound-healing assay, and proliferation assay were used to explore the function of lncRNA FTX in CRC cells. Quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and luciferase reporter assay were used to confirm the relationship between lncRNA FTX and miR-214-5p-jagged canonical Notch ligand 1 (JAG1). We further explored the role of lncRNA FTX in vivo using xenograft tumor assay.ResultslncRNA FTX was found to be upregulated in CRC tissues by FISH. The downregulation of endogenous lncRNA FTX expression inhibited CRC cell proliferation, migration, and invasion. Mechanistically, lncRNA FTX sequestered miR-214-5p and thus released its repression on JAG1, driving the malignant progression of CRC.ConclusionsThese findings give rise to a new perspective, the lncRNA FTX-miR-214-5p-JAG1 regulatory axis, in exploring the cancer-promoting mechanism of lncRNA FTX in CRC.
| S-EPMC8506562 | biostudies-literature
Project description:Bladder cancer (BC) is the most common genitourinary malignancy worldwide, and its aetiology and pathogenesis remain unclear. Accumulating evidence has shown that HAGLROS is closely related to the occurrence and progression of various cancers. However, the biological functions and underlying mechanisms of HAGLROS in BC remain unknown. In the present study, the expression of HAGLROS in BC was determined by public dataset analysis, transcriptome sequencing analysis, qRT-PCR and ISH assays. Gain- or loss-of-function assays were performed to study the biological roles of HAGLROS in BC cells and nude mouse xenograft model. Bioinformatic analysis, qRT-PCR, western blot, immunohistochemistry, FISH assays, subcellular fractionation assays and luciferase reporter assays were performed to explore the underlying molecular mechanisms of HAGLROS in BC. Here, we found that HAGLROS expression is significantly upregulated in BC tissues and cells, and elevated HAGLROS expression was related to higher pathologic grade and advanced clinical stage, which is significant for BC diagnosis. HAGLROS can enhance the growth and metastasis of BC in vitro and in vivo. Furthermore, miR-330-5p downregulation reversed the BC cells proliferation, migration and invasion inhibited by silencing HAGLROS. SPRR1B silencing restored the malignant phenotypes of BC cells promoted by miR-330--5p inhibitor. Mechanistically, we found that HAGLROS functions as a microRNA sponge to positively regulate SPRR1B expression by sponging miR-330-5p. Together, these results demonstrate that HAGLROS plays an oncogenic role and may serve as a potential biomarker for the diagnosis and treatment of BC.
| S-EPMC9159766 | biostudies-literature