scholarly journals Elevated Circular RNA PVT1 Promotes Eutopic Endometrial Cell Proliferation and Invasion of Adenomyosis via miR-145/Talin1 Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Yi-Yi Wang ◽  
Hua Duan ◽  
Sha Wang ◽  
Yong-Jun Quan ◽  
Jun-Hua Huang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Circular Rna ◽  
Endometrial Tissue ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Regulatory Effect ◽  
Endometrial Cell ◽  
Elevated Expression ◽  
Proliferation And Invasion

Several theories on the origin of adenomyosis (ADS) have been proposed, of which the most widely accepted is the fundamental pathogenic role of uterine eutopic endometrium. Emerging evidence suggests that circular RNAs participate in the multiple tumorgenesis. The vital importance of circular RNA PVT1 (circPVT1) in the pathological progress like malignancies has been well documented. Nevertheless, its underlying correlation with ADS remains elusive yet. The purpose of this study was to investigate the expression pattern, regulatory effect, and internal mechanism of circPVT1 in ADS. qRT-PCR was performed to detect the relative mRNA expression of circPVT1, miR-145, and Talin1 in ADS endometrial tissue and cells. The protein level of Talin1 was measured by Western blot and immunochemistry. Immunofluorescence was used to identify the primary endometrial epithelial and stromal cells. circPVT1 knockdown in vitro was achieved by transfecting with specific lentivirus vector CCK-8, and colony formation assays were utilized to assess cell proliferation; meanwhile, the transwell assay was employed for evaluating cell invasion ability. By conducting bioinformatics, dual-luciferase reporter assay, or RNA immunoprecipitation (RIP) experiment, the interaction between miR-145 and circPVT1 or Talin1 was verified. Rescue experiments further determined the regulatory effect of circPVT1/miR-145/Talin1 axis. We found both circPVT1 and Talin1 were markedly upregulated in ADS endometrial tissue and cells, whereas miR-145 was decreased. Elevated expression of circPVT1 was closely related to the severity of dysmenorrhea, menorrhagia, and uterine enlargement of patients with ADS. Knockdown of circPVT1 inhibited adenomyotic epithelial and stromal cell proliferation and invasion. Further mechanistic experiments revealed that circPVT1 negatively regulated miR-145 through serving as a molecular sponge. And the facilitating effect of circPVT1 was partially reversed by miR-145. Talin1 was demonstrated to be a down target of miR-145 and indirectly affected by circPVT1. Our findings unveiled that enhanced circPVT1 may be involved in the pathogenesis of ADS via stimulating endometrial cell proliferation and invasion. The establishment of circPVT1/miR-145/Talin1 pathway might present a novel therapeutic insight for ADS.

scholarly journals CircFOXO3 promotes glioblastoma progression by acting as a competing endogenous RNA for NFAT5

2019 ◽  
Vol 21 (10) ◽  
pp. 1284-1296 ◽  
Author(s):  
Shuai Zhang ◽  
Keman Liao ◽  
Zengli Miao ◽  
Qing Wang ◽  
Yifeng Miao ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Noncoding Rna ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Competing Endogenous Rna ◽  
Activated T Cells ◽  
Reverse Transcription Pcr ◽  
Proliferation And Invasion

Abstract Background Circular RNAs (circRNAs), a newly discovered type of endogenous noncoding RNA, have been proposed to mediate the progression of diverse types of tumors. Systematic studies of circRNAs have just begun, and the physiological roles of circRNAs remain largely unknown. Here, we focused on elucidating the potential role and molecular mechanism of circular forkhead box O3 (circFOXO3) in glioblastoma (GBM) progression. Methods First, we analyzed circFOXO3 alterations in GBM and noncancerous tissues through real-time quantitative reverse transcription PCR (qRT-PCR). Next, we used loss- and gain-of-function approaches to evaluate the effect of circFOXO3 on GBM cell proliferation and invasion. Mechanistically, fluorescent in situ hybridization, RNA pull-down, dual luciferase reporter, and RNA immunoprecipitation assays were performed to confirm the interaction between circFOXO3 and miR-138-5p/miR-432-5p in GBM. An animal model was used to verify the in vitro experimental findings. Results CircFOXO3 expression was significantly higher in GBM tissues than in noncancerous tissues. GBM cell proliferation and invasion were reduced by circFOXO3 knockdown and enhanced by circFOXO3 overexpression. Further biochemical analysis showed that circFOXO3 exerted its pro-tumorigenic activity by acting as a competing endogenous RNA (ceRNA) to increase expression of nuclear factor of activated T cells 5 (NFAT5) via sponging both miR-138-5p and miR-432-5p. Notably, tumor inhibition by circFOXO3 downregulation could be reversed by miR-138-5p/miR-432-5p inhibitors in GBM cells. Moreover, GBM cells with lower circFOXO3 expression developed less aggressive tumors in vivo. Conclusions Our data demonstrate that circFOXO3 can exert regulatory functions in GBM and that ceRNA-mediated microRNA sequestration might be a potential strategy for GBM therapy.

scholarly journals KLF7/VPS35 axis contributes to hepatocellular carcinoma progression through CCDC85C-activated β-catenin pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yarong Guo ◽  
Bao Chai ◽  
Junmei Jia ◽  
Mudan Yang ◽  
Yanjun Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Luciferase Reporter ◽  
Aberrant Expression ◽  
Proliferation And Invasion ◽  
Hcc Cells

Abstract Objective Dysregulation of KLF7 participates in the development of various cancers, but it is unclear whether there is a link between HCC and aberrant expression of KLF7. The aim of this study was to investigate the role of KLF7 in proliferation and migration of hepatocellular carcinoma (HCC) cells. Methods CCK8, colony growth, transwell, cell cycle analysis and apoptosis detection were performed to explore the effect of KLF7, VPS35 and Ccdc85c on cell function in vitro. Xenografted tumor growth was used to assess in vivo role of KLF7. Chip-qPCR and luciferase reporter assays were applied to check whether KLF7 regulated VPS35 at transcriptional manner. Co-IP assay was performed to detect the interaction between VPS35 and Ccdc85c. Immunohistochemical staining and qRT-PCR analysis were performed in human HCC sampels to study the clinical significance of KLF7, VPS35 and β-catenin. Results Firstly, KLF7 was highly expressed in human HCC samples and correlated with patients’ differentiation and metastasis status. KLF7 overexpression contributed to cell proliferation and invasion of HCC cells in vitro and in vivo. KLF7 transcriptional activation of VPS35 was necessary for HCC tumor growth and metastasis. Further, co-IP studies revealed that VPS35 could interact with Ccdc85c in HCC cells. Rescue assay confirmed that overexpression of VPS35 and knockdown of Ccdc85c abolished the VPS35-medicated promotion effect on cell proliferation and invasion. Finally, KLF7/VPS35 axis regulated Ccdc85c, which involved in activation of β-catenin signaling pathway, confirmed using β-catenin inhibitor, GK974. Functional studies suggested that downregulation of Ccdc85c partly reversed the capacity of cell proliferation and invasion in HCC cells, which was regulated by VPS35 upregulation. Lastly, there was a positive correlation among KLF7, VPS35 and active-β-catenin in human HCC patients. Conclusion We demonstrated that KLF7/VPS35 axis promoted HCC cell progression by activating Ccdc85c-medicated β-catenin pathway. Targeting this signal axis might be a potential treatment strategy for HCC.

scholarly journals Sevoflurane inhibits malignant progression of colorectal cancer via hsa_circ_0000231-mediated miR-622

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Jingpeng Wang ◽  
Shuyuan Li ◽  
Gaofeng Zhang ◽  
Huihua Han
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Volatile Anesthetic ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas

Abstract Background Sevoflurane (Sev), a commonly used volatile anesthetic, has been reported to inhibit the process of colorectal cancer (CRC). Circular RNAs (circRNAs) are revealed to participate in the pathogenesis of CRC. This study aims to reveal the mechanism of hsa_circ_0000231 in Sev-mediated CRC progression. Methods The expression of hsa_circ_0000231 and microRNA-622 (miR-622) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein level was determined by western blot analysis. Cell proliferation was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cell colony formation and DNA content quantitation assays. Cell apoptosis was detected by Annexin V-fluorescein isothiocyanate and propidium iodide double staining and caspase 3 activity assays. Cell migration and invasion were investigated by wound-healing and transwell invasion assays, respectively. The putative relationship between hsa_circ_0000231 and miR-622 was predicted by circular RNA Interactome online database, and identified by dual-luciferase reporter and RNA immunoprecipitation assays. The impacts of hsa_circ_0000231 on Sev-mediated tumor formation in vivo were presented by in vivo assay. Results Hsa_circ_0000231 expression was upregulated, while miR-622 was downregulated in CRC tissues and cells compared with control groups. Sev treatment decreased hsa_circ_0000231 expression, but increased miR-622 expression in CRC cells. Sev treatment suppressed cell proliferation, migration and invasion, and induced cell apoptosis. Hsa_circ_0000231 overexpression restored Sev-mediated CRC progression in vitro. Additionally, hsa_circ_0000231 acted as a sponge of miR-622, and miR-622 inhibitors reversed the impacts of hsa_circ_0000231 silencing on CRC process. Furthermore, Sev treatment inhibited tumor growth by regulating hsa_circ_0000231 in vivo. Conclusion Hsa_circ_0000231 attenuated Sev-aroused repression impacts on CRC development by sponging miR-622. This findings may provide an appropriate anesthetic protocol for CRC sufferers undergoing surgery.

scholarly journals Thymosin-β4 Mediates Hepatic Stellate Cell Activation by Interfering with CircRNA-0067835/miR-155/FoxO3 Signaling Pathway

2018 ◽  
Vol 51 (3) ◽  
pp. 1389-1398 ◽  
Author(s):  
Lili Zhu ◽  
Tingting Ren ◽  
Zixin Zhu ◽  
Mingliang  Cheng ◽  
Qiuju Mou ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Cell Activation ◽  
Stellate Cell ◽  
Circular Rna ◽  
Fine Tuning ◽  
Differentially Expressed ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
G1 Arrest

Background/Aims: Hepatic stellate cells (HSCs) are the primary cell type responsible for liver fibrosis. Our study proved that thymosin beta 4 (Tβ4) has anti-fibrogenic effects in HSCs through PI3K/AKT pathway. However, the underlying mechanisms are not fully elucidated. Circular RNAs (circRNAs) play important roles in fine-tuning gene expression and are often deregulated in cancers. However, the expression profile and clinical significance of in liver fibrosis is still unknown. Therefore, we hypothesize that Tβ4 influences circRNAs in liver fibrosis. Methods: Circular RNA microarray was conducted to identify Tβ4-related circRNAs. Pathway analysis and miRNA response elements analysis was conducted to predict the potential roles of differentially expressed circRNAs in liver fibrosis. CCK8 assays and flow cytometric assays were conducted to clarify the role of circRNA in liver fibrosis. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in liver fibrosis. Results: A total of 644 differentially expressed circRNAs were identified between the Tβ4-depleted LX-2 cells and the control LX2 cells. The expression of circRNA-0067835 was significantly increased in the Tβ4-depleted LX-2 cells compared with control. Knockdown of circRNA-0067835 observably decreased LX-2 cell proliferation by causing G1 arrest and promoting apoptosis. Bioinformatics online programs predicted that circRNA-0067835 acted as miR-155 sponge to regulate FOXO3a expression, which was validated using luciferase reporter assay. Conclusion: Our experiments showed that circRNA-0067835 regulated liver fibrosis progression by acting as a sponge of miR-155 to promote FOXO3a expression, indicating that circRNA-0067835 may serve as a potential therapeutic target for patients with liver fibrosis.

scholarly journals Circular RNA circFAT1(e2) Promotes Colorectal Cancer Tumorigenesis via the miR-30e-5p/ITGA6 Axis

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Fei Pan ◽  
Dongqing Zhang ◽  
Na Li ◽  
Mei Liu
Keyword(s):  
Colorectal Cancer ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Small Interfering Rnas ◽  
Regulatory Relationship ◽  
Downstream Target ◽  
Normal Tissues

circRNAs (circular RNAs) are a family of noncoding RNAs and have diverse physiological and pathological functions. However, the functions and mechanisms of circRNAs in the development and progression of colorectal cancer (CRC) remain largely unknown. Here, we aimed to explore the functions and roles of circFAT1(e2) in CRC. qRT-PCR revealed that circFAT1(e2) in CRC tumor tissues was upregulated compared with that in adjacent normal tissues and was also upregulated in CRC cell lines. Small interfering RNAs (siRNAs) against circFAT1(e2) were used to decrease the expression of circFAT1(e2) in HCT116 and RKO cells in vitro. The roles of circFAT1(e2) in CRC cell metastasis and proliferation were then determined by transwell and CCK-8 assays. The results showed that circFAT1(e2) silencing markedly suppressed CRC growth. Moreover, we identified circFAT1(e2) as a promoter of CRC metastasis. Knockdown of circFAT1(e2) evidently reduced HCT116 and RKO cell migration and invasion. Furthermore, the regulatory relationship between circFAT1(e2) and its target miRNAs was verified by a luciferase reporter assay. We demonstrated that circFAT1(e2) could sponge miR-30e-5p, which regulated the expression level of integrin α6 (ITGA6), the downstream target gene of miR-30e-5p. Rescue assays demonstrated that knockdown of miR-30e-5p enhanced CRC proliferation and migration via ITGA6. Taken together, our results reveal the novel oncogenic roles of circFAT1(e2) in CRC through the miR-30e-5p/ITGA6 axis.

scholarly journals Circular RNA circCCDC66 Contributes to Malignant Phenotype of Osteosarcoma by Sponging miR-338-3p to Upregulate the Expression of PTP1B

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Deng Xiang ◽  
Yugang Li ◽  
Yanshui Lin
Keyword(s):  
Cell Proliferation ◽  
Molecular Mechanism ◽  
Cell Lines ◽  
Rapid Development ◽  
Circular Rna ◽  
Molecular Medicine ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Tissue Samples

In recent years, the mechanism of cancer research has become hotspots of life science and medicine, especially due to the rapid development of molecular medicine and bioinformatics research. Similarly, the molecular mechanism also has received increasing attention in osteosarcoma (OS) research. Also, a considerable amount of research confirmed that circular RNAs (circRNAs) could regulate cancer cell growth and metastasis. This study aimed to explore the effect of a circRNA, circCCDC66, on OS and reveal its potential molecular mechanism. High circCCDC66 expression level was found in OS patient-derived tissue samples and OS cell lines by qRT-PCR. The abilities cell proliferation and metastatic of U2OS and SW1353 cells were then assessed by Cell Counting Kit-8 and transwell assay, respectively. The interaction between circCCDC66 and its target miRNAs were verified by the dual-luciferase reporter assay. Through functional experiments, we found that circCCDC66 knockdown promoted the inhibition of cell proliferation and metastatic of OS cell lines. From mechanistic perspective, circCCDC66 upregulated PTP1B by sponging miR-338-3p. Collectively, our findings demonstrated that circCCDC66 contributed to malignant behaviors of OS cells by miR-338-3p/PTP1B pathway, which suggested circCCDC66/miR-338-3p/PTP1B axis might be a potential therapeutic target.

scholarly journals Circ_0001421 facilitates glycolysis and lung cancer development by regulating miR-4677-3p/CDCA3

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Koudong Zhang ◽  
Hang Hu ◽  
Juan Xu ◽  
Limin Qiu ◽  
Haitao Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Tumor Progression ◽  
Lactate Production ◽  
Tumor Formation ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Glucose Assay

Abstract Background Lung cancer (LC) is a malignant tumor originating in the bronchial mucosa or gland of the lung. Circular RNAs (circRNAs) are proved to be key regulators of tumor progression. However, the regulatory effect of circ_0001421 on lung cancer tumorigenesis remains unclear. Methods The expression levels of circ_0001421, microRNA-4677-3p (miR-4677-3p) and cell division cycle associated 3 (CDCA3) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Methyl thiazolyl tetrazolium (MTT), Transwell and Tumor formation assays were performed to explore the role of circ_0001421 in LC. Glucose consumption and lactate production were examined by a Glucose assay kit and a Lactic Acid assay kit. Western blot was utilized to examine the protein levels of Hexokinase 2 (HK2) and CDCA3. The interaction between miR-4677-3p and circ_0001421 or CDCA3 was confirmed by dual-luciferase reporter assay. Results Circ_0001421 was increased in LC tissues and cells, and knockdown of circ_0001421 repressed cell proliferation, migration, invasion and glycolysis in vitro. Meanwhile, circ_0001421 knockdown inhibited LC tumor growth in vivo. Mechanistically, circ_0001421 could bind to miR-4677-3p, and CDCA3 was a target of miR-4677-3p. Rescue assays manifested that silencing miR-4677-3p or CDCA3 overexpression reversed circ_0001421 knockdown-mediated suppression on cell proliferation, migration, invasion and glycolysis in LC cells. Conclusion Circ_0001421 promoted cell proliferation, migration, invasion and glycolysis in LC by regulating the miR-4677-3p/CDCA3 axis, which providing a new mechanism for LC tumor progression.

scholarly journals EIF4A3-induced circular RNA MMP9 (circMMP9) acts as a sponge of miR-124 and promotes glioblastoma multiforme cell tumorigenesis

2018 ◽  
Vol 17 (1) ◽  
Author(s):  
Renjie Wang ◽  
Sai Zhang ◽  
Xuyi Chen ◽  
Nan Li ◽  
Jianwei Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glioblastoma Multiforme ◽  
Aurora Kinase ◽  
Underlying Mechanism ◽  
Circular Rna ◽  
Initiation Factor ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Reporter Assays

Abstract Background Circular RNAs (circRNAs) have been found to play critical roles in the development and progression of various cancers. However, little is known about the effects of the circular RNA network on glioblastoma multiforme (GBM). Methods A microarray was used to screen circRNA expression in GBM. Quantitative real-time PCR was used to detect the expression of circMMP9. GBM cells were transfected with a circMMP9 overexpression vector or siRNA, and cell proliferation, migration and invasion, as well as tumorigenesis in nude mice, were assessed to examine the effect of circMMP9 in GBM. Biotin-coupled miRNA capture, fluorescence in situ hybridization and luciferase reporter assays were conducted to confirm the relationship between circMMP9 and miR-124. Results In this study, we screened differentially expressed circRNAs and identified circMMP9 in GBM. We found that circMMP9 acted as an oncogene, was upregulated in GBM and promoted the proliferation, migration and invasion abilities of GBM cells. Next, we verified that circMMP9 served as a sponge that directly targeted miR-124; circMMP9 accelerated GBM cell proliferation, migration and invasion by targeting miR-124. Furthermore, we found that cyclin-dependent kinase 4 (CDK4) and aurora kinase A (AURKA) were involved in circMMP9/miR-124 axis-induced GBM tumorigenesis. Finally, we found that eukaryotic initiation factor 4A3 (eIF4A3), which binds to the MMP9 mRNA transcript, induced circMMP9 cyclization and increased circMMP9 expression in GBM. Conclusions Our findings indicate that eIF4A3-induced circMMP9 is an important underlying mechanism in GBM cell proliferation, invasion and metastasis through modulation of the miR-124 signaling pathway, which could provide pivotal potential therapeutic targets for the treatment of GBM. Graphical abstract

scholarly journals TP53-Activated lncRNA GHRLOS Regulates Cell Proliferation, Invasion, and Apoptosis of Non-Small Cell Lung Cancer by Modulating the miR-346/APC Axis

2021 ◽  
Vol 11 ◽  
Author(s):  
Ke Ren ◽  
Jinghui Sun ◽  
Lingling Liu ◽  
Yuping Yang ◽  
Honghui Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Qrt Pcr ◽  
Proliferation And Invasion

Non-small cell lung cancer (NSCLC) is the main type of lung cancer with high mortality worldwide. To improve NSCLC therapy, the exploration of molecular mechanisms involved in NSCLC progression and identification of their potential therapy targeting is important. Long noncoding RNAs (lncRNAs) have shown important roles in regulating various tumors progression, including NSCLC. We found lncRNA GHRLOS was decreased in NSCLC cell lines and tissues which correlated with poor prognosis of NSCLC patients. However, the role and underlying mechanisms of lncRNA GHRLOS in NSCLC progression remains elusive. The expression of lncRNA GHRLOS was examined in NSCLC cell lines and biopsy specimens of patients with NSCLC by quantitative real time polymerase chain reaction (qRT-PCR). The effects of GHRLOS on proliferation, invasion and apoptosis of NSCLC cells were determined by both in vitro and in vivo experiments. The interaction between GHRLOS and TP53 was determined by dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) combined with qRT-PCR analysis. RNA immunoprecipitation (RIP) was conducted to validate the binding between GHRLOS and microRNA-346 (miR-346). Dual-luciferase reporter assays were also carried out to reveal the interaction between miR-346 and the 3’ untranslated region (3’UTR) of adenomatous polyposis coli (APC) mRNA.Our data demonstrated that overexpression of lncRNA GHRLOS suppressed cancer cell proliferation and invasion as well as promoted cell apoptosis by regulating the expression of CDK2, PCNA, E-cadherin, N-cadherin, Bax, and Bcl-2 in NSCLC cells. Moreover, lncRNA GHRLOS was upregulated by the binding of TP53 to the GHRLOS promoter. The binding target of lncRNA GHRLOS was identified to be miR-346. Impressively, overexpression of miR-346 promoted cell proliferation and invasion, as well as inhibited cell apoptosis, however, these effects can be blocked by overexpression of lncRNA GHRLOS both in vitro and in vivo. In summary, this study reveals lncRNA GHRLOS, upregulated by TP53, acts as a molecule sponge of miR-346 to cooperatively modulates expression of APC, a miR-346 target, and potentially inhibits NSCLC progression via TP53/lncRNA GHRLOS/miR-346/APC axis, which represents a novel pathway that could be useful in targeted therapy against NSCLC.

scholarly journals LncRNA NONHSAT114552 Sponges miR-320d to Promote Proliferation and Invasion of Chordoma Through Upregulating NRP1

2021 ◽  
Vol 12 ◽  
Author(s):  
Kai Zhang ◽  
Zixiang Liu ◽  
Yingchuang Tang ◽  
Xiaofeng Shao ◽  
Xi Hua ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Clinical Prognosis ◽  
Kaplan Meier ◽  
Neuropilin 1 ◽  
Competitive Endogenous Rnas ◽  
Proliferation And Invasion

Chordoma is a relatively rare malignant bone tumor with high local recurrence. To date, the mechanism remains unclear. lncRNAs play a pivotal role in tumorigenesis by acting as competitive endogenous RNAs of microRNAs. However, the biological role of lncRNA is still unclear in chordoma. In this research, our aim is to investigate the roles and regulation mechanisms of lncRNA NONHSAT114552 in chordoma development. The expression level of NONHSAT114552 and miR-320d in chordoma tissues was determined by qRT-PCR. Meantime, the correlation between NONHSAT114552 and clinical prognosis was also studied. Bioinformatics analysis and luciferase reporter assays were used to verify the relationship between NONHSAT114552 and miR-320d, and between miR-320d and Neuropilin 1 (NRP1). In addition, effects of NONHSAT114552 on chordoma cells (U-CH1 and U-CH2) proliferation and invasion and its regulation on miR-320d were also evaluated. Furthermore, the influences of NONHSAT114552/miR-320d/NRP1 axis on chordoma tumorigenesis were investigated in vivo. NONHSAT114552 was overexpressed while miR-320d was down-regulated in chordoma tissue compared to fetal nucleus pulposus. Kaplan-Meier survival analysis showed that NONHSAT114552 overexpression was associated with patients’ poor prognosis. Knockdown of NONHSAT114552 significantly suppressed chordoma cell proliferation and invasion. In vitro studies confirmed that NONHSAT114552 acted as ceRNA to regulate NRP1 by directly sponging miR-320d, thus facilitating chordoma cell proliferation and invasion. In vivo study demonstrated that NONHSAT114552 moderated chordoma growth by sponging miR-320d to regulating NRP1. Our findings indicate that lncRNA NONHSAT114552 exhibits a critical role in the tumorigenesis and development of chordoma and it may become one potential prognostic marker and therapeutic target for this disease. .

Sign in / Sign up

Export Citation Format

Share Document