scholarly journals CircRNA PIP5K1A promotes the progression of glioma through upregulation of the TCF12/PI3K/AKT pathway by sponging miR-515-5p

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kebin Zheng ◽  
Haipeng Xie ◽  
Wensong Wu ◽  
Xichao Wen ◽  
Zhaomu Zeng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Glioma Cell ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Circular Rnas ◽  
Rt Pcr ◽  
Mesenchymal Transition

Abstract Background Increasing studies have revealed that circular RNAs (CircRNAs) make great contributions to regulating tumor progression. Therefore, we intended to explore the expression characteristics, function, and related mechanisms of a novel type of circRNA, PIP5K1A, in glioma. Methods Firstly, reverse transcription-polymerase chain reaction (RT-PCR) was carried out to examine CircPIP5K1A expression in glioma tissues and adjacent normal tissues, and the correlation between CircPIP5K1A level and the clinical-pathological indicators of glioma was analyzed. Then, the CircPIP5K1A expression in various glioma cell lines was detected, and CircPIP5K1A overexpression and knockdown cell models were constructed. Subsequently, cell proliferation and viability were detected by the CCK8 method and BrdU staining. Cell apoptosis was detected by flow cytometry, and cell invasion was examined by Transwell assay. The expression of TCF12, PI3K/AKT pathway apoptotic related proteins (Caspase3, Bax, and Bcl2) and epithelial-mesenchymal transition (EMT) markers (E-cadherin, Vimentin, and N-cadherin) was determined by western blot or RT-PCR. Results The results manifested that CircPIP5K1A was upregulated in glioma tissues (compared with that in normal adjacent tissues), and overexpressed CircPIP5K1A was related to glioma volume and histopathological grade. Functionally, overexpressing CircPIP5K1A notably elevated glioma cell proliferation, invasion, and EMT and inhibited apoptosis both in vivo and in vitro. Besides, CircPIP5K1A upregulated TCF12 and PI3K/AKT activation. Bioinformatics analysis testified that miR-515-5p was a common target of CircPIP5K1A and TCF12, while the dual-luciferase reporter assay and RNA immunoprecipitation (RIP) experiment further confirmed that CircPIP5K1A targeted miR-515-5p, which bound the 3′-untranslated region (UTR) of TCF12. Conclusions Overall, the study illustrated that CircPIP5K1A is a potential prognostic marker in glioma and regulates glioma evolvement by modulating the miR-515-5p-mediated TCF12/PI3K/AKT axis.

scholarly journals CircRNA PIP5K1A promotes the progression of glioma through upregulation of TCF12/PI3K/AKT pathway by sponging miR-515-5p

2020 ◽  
Author(s):  
Kebin Zheng ◽  
Haipeng Xie ◽  
Xiaosong Wu ◽  
Xichao Wen ◽  
Zhaomu Zeng ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Cell Model ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Circular Rnas ◽  
Rt Pcr ◽  
Mesenchymal Transition ◽  
Normal Tissues

Abstract BackgroundIncreasing studies have revealed that circular RNAs (CircRNAs) make great contribution to regulating tumor progression. Therefore, we intended to explore the expression characteristics, function, and related mechanisms of a novel type of circRNA, PIP5K1A in glioma. MethodsFirstly, RT-PCR was carried out to examine CircPIP5K1A expression in glioma tissues and adjacent normal tissues, and the correlation between CircPIP5K1A level and the clinical pathological indicators of glioma was analyzed. Then, the CircPIP5K1A expression in various glioma cell lines was detected, and a cell model of CircPIP5K1A overexpression and knockdown was constructed. Subsequently, cell proliferation and viability were detected by CCK8 method and BrdU staining, apoptosis was detected by flow cytometry, and cell invasion was examined by Transwell assay. The expression of TCF12, PI3K/AKT pathway apoptotic related proteins (including Caspase3, Bax and Bcl2) and epithelial-mesenchymal transition (EMT) markers (including E-cadherin, Vimentin and N-cadherin) by western blot or RT-PCR. ResultsThe results manifested that CircPIP5K1A was obviously upregulated in glioma tissues (compared with that in normal adjacent tissues), and overexpressed CircPIP5K1A was distinctly related to glioma volume and histopathological grade. Functionally, overexpressing CircPIP5K1A notably elevated the proliferation, invasion, EMT of glioma cells, and inhibited apoptosis both in vivo and in vitro. Besides, CircPIP5K1A also upregulated TCF12 and PI3K/AKT pathway activation. Bioinformatics analysis testified that miR-515-5p was a common target of CircPIP5K1A and TCF12, while dual luciferase reporter assay and RNA immunocoprecipitation (RIP) experiment further confirmed that CircPIP5K1A targeted miR-515-5p, which bound the 3'-untranslated region (UTR) of TCF12. ConclusionsAltogether, the study illustrated that CircPIP5K1A is a potential prognostic marker in glioma and regulates the development of glioma through the modulating miR-515-5p mediated TCF12/PI3K/AKT axis.

scholarly journals Circ_0026416 downregulation blocks the development of colorectal cancer through depleting MYO6 expression by enriching miR-545-3p

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lei Zhang ◽  
Ranran Yu ◽  
Chunhua Li ◽  
Yu Dang ◽  
Xiaoyu Yi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Colony Formation ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
List Type ◽  
Mesenchymal Transition

Abstract Background Emerging evidence reveals that the initiation and development of human cancers, including colorectal cancer (CRC), are associated with the deregulation of circular RNAs (circRNAs). Our study intended to disclose the role of circ_0026416 in the malignant behaviors of CRC. Methods The detection for circ_0026416 expression, miR-545-3p expression, and myosin VI (MYO6) mRNA expression was performed using quantitative real-time PCR (qPCR). CCK-8 assay, colony formation assay, transwell assay, and flow cytometry assay were applied for functional analysis to monitor cell proliferation, migration, invasion, and apoptosis. The protein levels of MYO6 and epithelial mesenchymal-transition (EMT) markers were detected by western blot. Mouse models were used to determine the role of circ_0026416 in vivo. The potential relationship between miR-545-3p and circ_0026416 or MYO6 was verified by dual-luciferase reporter assay and RIP assay. Results The expression of circ_0026416 was increased in CRC tumor tissues and cell lines. Circ_0026416 downregulation inhibited CRC cell proliferation, colony formation, migration, invasion, and EMT but induced cell apoptosis in vitro, and circ_0026416 knockdown also blocked tumor growth in vivo. MiR-545-3p was a target of circ_0026416, and rescue experiments indicated that circ_0026416 knockdown blocked CRC development by enriching miR-545-3p. In addition, miR-545-3p targeted MYO6 and inhibited MYO6 expression. MiR-545-3p enrichment suppressed CRC cell malignant behaviors by sequestering MYO6. Importantly, circ_0026416 knockdown depleted MYO6 expression by enriching miR-545-3p. Conclusion Circ_0026416 downregulation blocked the development of CRC through depleting MYO6 expression by enriching miR-545-3p. Highlights Circ_0026416 downregulation inhibits CRC development in vitro and in vivo. Circ_0026416 regulates the expression of MYO6 by targeting miR-545-3p. Circ_0026416 governs the miR-545-3p/MYO6 axis to regulate CRC progression.

scholarly journals Circular RNA circFGD4 suppresses gastric cancer progression via modulating miR-532-3p/APC/β-catenin signalling pathway

2020 ◽  
Author(s):  
Xinglong Dai ◽  
Jianjun Liu ◽  
Xiong Guo ◽  
Anqi Cheng ◽  
Xiaoya Deng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Viability ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Potential Biomarker

Background: Mounting evidence has displayed critical roles of circular RNAs (circRNAs) in multiple cancers. The underlying mechanisms by which circFGD4 contributed to gastric cancer (GC) are still unclear. Methods: The levels and clinical values of circFGD4 in GC patients were detected and analysed by quantitative real-time PCR. The biological roles of circFGD4 in GC were assessed in vitro and in vivo experiments. Dual-luciferase reporter, fluorescence in situ hybridization, RNA immunoprecipitation, biotin-coupled RNA pull-down, and TOP/Flash and FOP/Flash reporter gene assays were employed to evaluate the effects of circFGD4 on miR-532-3p-mediated adenomatous polyposis coli (APC)/β-catenin signalling in GC cells. Results: circFGD4 expression was down-regulated the most in human GC tissues and cell lines. Low expression of circFGD4 was correlated with poor tumour differentiation, lymphatic metastasis, and poor prognosis of GC patients. circFGD4 suppressed GC cell viability, colony formation, migration, induced epithelial-mesenchymal transition (EMT) and tumorigenesis and metastasis in vivo. Next, we validated that circFGD4 acted as a sponge of miR-532-3p to relieve the tumour-promoting effects of miR-532-3p on its target APC. The mechanistic analysis demonstrated that the circFGD4 suppressed GC cell viability, migration, and EMT by modulating the miR-532-3p/APC axis to inactivate the β-catenin signalling. Conclusion: circFGD4 suppressed GC progression through sponging miR-532-3p and enhancing APC expression to inactivate the β-catenin signalling. Thus circFGD4 provides a novel potential biomarker and valuable therapeutic strategy for GC.

scholarly journals The POU2F1/miR-4490/USP22 axis regulates cell proliferation and metastasis in gastric cancer

2020 ◽  
Vol 43 (6) ◽  
pp. 1017-1033 ◽  
Author(s):  
Yizhi Xiao ◽  
Side Liu ◽  
Jiaying Li ◽  
Weiyu Dai ◽  
Weimei Tang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Epithelial Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Aberrant Expression ◽  
Mesenchymal Transition

Abstract Purpose Growing evidence indicates that aberrant expression of microRNAs contributes to tumor development. However, the biological role of microRNA-4490 (miR-4490) in gastric cancer (GC) remains to be clarified. Methods To explore the function of miR-4490 in GC, we performed colony formation, EdU incorporation, qRT-PCR, Western blotting, in situ hybridization (ISH), immunohistochemistry (IHC), flow cytometry, ChIP and dual-luciferase reporter assays. In addition, the growth, migration and invasion capacities of GC cells were evaluated. Results We found that miR-4490 was significantly downregulated in primary GC samples and in GC-derived cell lines compared with normal controls, and that this expression level was negatively correlated with GC malignancy. Exogenous miR-4490 expression not only reduced cell cycle progression and proliferation, but also significantly inhibited GC cell migration, invasion and epithelial-mesenchymal transition (EMT) in vitro. Mechanistically, we found that miR-4490 directly targets USP22, which mediates inhibition of GC cell proliferation and EMT-induced metastasis in vitro and in vivo. Moreover, we found through luciferase and ChIP assays that transcription factor POU2F1 can directly bind to POU2F1 binding sites within the miR-4490 and USP22 promoters and, by doing so, modulate their transcription. Spearman’s correlation analysis revealed a positive correlation between USP22 and POU2F1 expression and negative correlations between miR-4490 and USP22 as well as miR-4490 and POU2F1 expression in primary GC tissues. Conclusion Based on our results we conclude that miR-4490 acts as a tumor suppressor, and that the POU2F1/miR-4490/USP22 axis plays an important role in the regulation of growth, invasion and EMT of GC cells.

scholarly journals Circular RNA hsa_circ_0003288 induces EMT and invasion by regulating hsa_circ_0003288/miR-145/PD-L1 axis in hepatocellular carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guili Xu ◽  
Peng Zhang ◽  
Hansi Liang ◽  
Yunhua Xu ◽  
Jian Shen ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Circular Rna ◽  
In Vivo Studies ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Huh7 Cells ◽  
And Function

Abstract Background Epithelial-mesenchymal transition (EMT) has been associated with wound healing, tumorigenesis, and metastasis. Circular RNAs (circRNAs) are functional non-coding RNAs involved in multiple human cancers. However, whether and how circRNAs contribute to the EMT in hepatocellular carcinomas (HCC) remains to be deciphered. In this study, we investigated the regulation and function of hsa_circ_0003288 on programmed death-1 ligand 1 (PD-L1) during EMT and HCC invasiveness. Methods Hsa_circ_0003288 expression was measured by real-time quantitative reverse transcriptase PCR (qRT-PCR). Luciferase reporter assays, RNA pull-down assay and fluorescence in situ hybridization (FISH) were used to determine the correlation between hsa_circ_0003288 and miR-145 and between miR-145 and PD-L1. Furthermore, ectopic overexpression and siRNA-mediated downregulation of hsa_circ_0003288, transwell assays, and in vivo studies were used to determine the function of hsa_circ_0003288 on the EMT and invasiveness of L02 and HCC cells. Results miR-145 directly targeted the PD-L1 3′-untranslated region (UTR) region, and hsa_circ_0003288 acted as a miR-145 sponge to regulate PD-L1 expression. Overexpression of hsa_circ_0003288 increased PD-L1 levels and promoted EMT, migration, and invasiveness of L02 cells. These observations were reversed after knockdown of hsa_circ_0003288 in HepG2 and Huh7 cells. Overexpression of PD-L1 rescued EMT, migration, and invasiveness of HepG2 and Huh7 cells after knockdown of hsa_circ_0003288. Furthermore, hsa_circ_0003288 knockdown reduced EMT in in vivo studies. Hsa_circ_0003288/PD-L1 axis was found to mediate the metastatic phenotypes via the PI3K/Akt pathway in HCC. Additionally, expression levels of hsa_circ_0003288 were increased and positively correlated with PD-L1 expression in HCC tissues. Conclusion Our findings demonstrated that hsa_circ_0003288 promoted EMT and invasion of HCC via the hsa_circ_0003288/miR-145/PD-L1 axis through the PI3K/Akt pathway. Targeting hsa_circ_0003288 may be a therapeutic strategy for the treatment of HCC.

scholarly journals CircRNA circ_0004370 promotes cell proliferation, migration, and invasion and inhibits cell apoptosis of esophageal cancer via miR-1301-3p/COL1A1 axis

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 104-116
Author(s):  
Xiaobo Chen ◽  
Hongwen Sun ◽  
Yunping Zhao ◽  
Jing Zhang ◽  
Guosheng Xiong ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Ec Cells

AbstractBackgroundThe aim of this study was to investigate the circ_0004370 expression in EC, its effects on cell proliferation, apoptosis, migration, invasion, and epithelial–mesenchymal transition (EMT) process, and the underlying regulatory mechanisms in EC.MethodsThe protein levels of COL1A1 and EMT-related proteins were detected by western blot. The role of circ_0004370 on cell viability, proliferation, and apoptosis was analyzed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay, and flow cytometry, respectively. The transwell assay was used to examine cell migration and invasion. The binding sites between miR-1301-3p and circ_0004370 or COL1A1 were predicted by starbase software and confirmed by dual-luciferase reporter assay and RNA pull-down assay.ResultsWe discovered that circ_0004370 was remarkably upregulated in EC tissues and cells. Knockdown of circ_0004370 inhibited cell proliferation, migration as well as invasion, and promoted apoptosis in vitro, while its effect was rescued by miR-1301-3p inhibition. And circ_0004370 mediated the EMT process in EC cells. Moreover, we explored its regulatory mechanism and found that circ_0004370 directly bound to miR-1301-3p and COL1A1 was verified as a target of miR-1301-3p. COL1A1 was highly expressed in EC cells and upregulation of COL1A1 reversed the effects of miR-1301-3p on cell proliferation, migration, invasion, and apoptosis. In addition, silencing of circ_0004370 reduced tumor volumes and weights in vivo. We showed that circ_0004370/miR-1301-3p/COL1A1 axis played the critical role in EC to regulate the cell activities.ConclusionCirc_0004370 promotes EC proliferation, migration and invasion, and EMT process and suppresses apoptosis by regulating the miR-1301-3p/COL1A1 axis, indicating that circ_0004370 may be used as a potential therapeutic target for EC.

scholarly journals Circ-ABCB10 knockdown inhibits the malignant progression of cervical cancer through microRNA-128-3p/ZEB1 axis

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Wei Feng ◽  
Ruixia Guo ◽  
Dongya Zhang ◽  
Ruitao Zhang
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Epithelial Mesenchymal Transition ◽  
Figo Stage ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Gynecology And Obstetrics

Abstract Aims We focused on the detailed functions of circ-ABCB10 in cervical cancer (CC) development and its mechanisms. Background The increasing findings have proposed the central roles of circular RNAs (circRNAs) in the tumorigenesis of various human cancers. Circ-ABCB10 displays promising oncogenic effect in several tumors. Methods Circ-ABCB10 and miR-128-3p production levels in CC tissues and cells were tested through RT-qPCR. The association of circ-ABCB10 expression with clinicopathologic parameters of CC patients was statistically analyzed. Cell proliferation, invasion, apoptosis, and epithelial-mesenchymal transition (EMT) were evaluated by MTT, transwell invasion assays, flow cytometry analyses, and western blot examination of EMT markers. The binding activity between miR-128-3p and circ-ABCB10 or zinc finger E-box binding homeobox 1 (ZEB1) was explored through pull-down assay or luciferase reporter assay. The influence of circ-ABCB10 on CC tumorigenesis was evaluated by in vivo xenograft experiments. Results The elevated circ-ABCB10 expression was determined in CC tissues and cells. Moreover, higher production level of circ-ABCB10 was close related to lymph-node metastasis, Federation of Gynecology and Obstetrics (FIGO) stage, and tumor size in CC patients. Loss of circ-ABCB10 weakened cell proliferative and invasive abilities, inhibited EMT, and induced apoptosis in CC. Loss of circ-ABCB10 inhibited ZEB1 expression by serving as a sponge of miR-128-3p in CC cells. Circ-ABCB10 sponged miR-128-3p to enhance cell proliferation, invasion, EMT and inhibit apoptosis in CC cells. Xenograft tumor assays confirmed that circ-ABCB10 knockdown inhibited CC tumor growth. Conclusion Our study suggests that circ-ABCB10 depletion inhibits proliferation, invasion and EMT and promotes apoptosis of cervical cancer cells through miR-128-3p/ZEB1 axis and represses CC tumor growth.

scholarly journals CircWAC induces chemotherapeutic resistance in triple-negative breast cancer by targeting miR-142, upregulating WWP1 and activating the PI3K/AKT pathway

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Lei Wang ◽  
Yehui Zhou ◽  
Liang Jiang ◽  
Linlin Lu ◽  
Tiantian Dai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Circular Rnas ◽  
Chemotherapeutic Resistance ◽  
Repressive Effect

Abstract Background Chemotherapeutic resistance is the main cause of clinical treatment failure and poor prognosis in triple-negative breast cancer (TNBC). There is no research on chemotherapeutic resistance in TNBC from the perspective of circular RNAs (circRNAs). Methods TNBC-related circRNAs were identified based on the GSE101124 dataset. Quantitative reverse transcription PCR was used to detect the expression level of circWAC in TNBC cells and tissues. Then, in vitro and in vivo functional experiments were performed to evaluate the effects of circWAC in TNBC. Results CircWAC was highly expressed in TNBC and was associated with worse TNBC patient prognosis. Subsequently, it was verified that downregulation of circWAC can increase the sensitivity of TNBC cells to paclitaxel (PTX) in vitro and in vivo. The expression of miR-142 was negatively correlated with circWAC in TNBC. The interaction between circWAC and miR-142 in TNBC cells was confirmed by RNA immunoprecipitation assays, luciferase reporter assays, pulldown assays, and fluorescence in situ hybridization. Mechanistically, circWAC acted as a miR-142 sponge to relieve the repressive effect of miR-142 on its target WWP1. In addition, the overall survival of TNBC patients with high expression of miR-142 was significantly better than that of patients with low expression of miR-142, and these results were verified in public databases. MiR-142 regulated the expression of WWP1 and the activity of the PI3K/AKT pathway. It was confirmed that WWP1 is highly expressed in TNBC and that the prognosis of patients with high WWP1 expression is poor. Conclusions CircWAC/miR-142/WWP1 form a competing endogenous RNA (ceRNA) network to regulate PI3K/AKT signaling activity in TNBC cells and affect the chemosensitivity of cells.

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 Sp1-Induced Upregulation of LBX2-AS1 Aggravates The Progression of Glioblastoma By Targeting The miR-491-5p/LIF Axis

2021 ◽  
Author(s):  
Wentao Li ◽  
Ismatullah Soufiany ◽  
Xiao Lyu ◽  
Lin Zhao ◽  
Chenfei Lu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Stat3 Signaling ◽  
Regulatory Effects

Abstract Background: Mounting evidences have shown the importance of lncRNAs in tumorigenesis and cancer progression. LBX2-AS1 is an oncogenic lncRNA that has been found abnormally expressed in gastric cancer and lung cancer samples. Nevertheless, the biological function of LBX2-AS1 in glioblastoma (GBM) and potential molecular mechanism are largely unclear. Methods: Relative levels of LBX2-AS1 in GBM samples and cell lines were detected by qRT-PCR and FISH. In vivo and in vitro regulatory effects of LBX2-AS1 on cell proliferation, epithelial-to-mesenchymal transition (EMT) and angiogenesis in GBM were examined through xenograft models and functional experiments, respectively. The interaction between Sp1 and LBX2-AS1 was assessed by ChIP. Through bioinformatic analyses, dual-luciferase reporter assay, RIP and Western blot, the regulation of LBX2-AS1 and miR-491-5p on the target gene leukemia Inhibitory factor (LIF) was identified. Results: LBX2-AS1 was upregulated in GBM samples and cell lines, and its transcription was promoted by binding to the transcription factor Sp1. As a lncRNA mainly distributed in the cytoplasm, LBX2-AS1 upregulated LIF, and activated the LIF/STAT3 signaling by exerting the miRNA sponge effect on miR-491-5p, thus promoting cell proliferation, EMT and angiogenesis in GBM. Besides, LBX2-AS1 was unfavorable to the progression of glioma and the survival. Conclusion: Upregulated by Sp1, LBX2-AS1 promotes the progression of GBM by targeting the miR-491-5p/LIF axis. It is suggested that LBX2-AS1 may be a novel diagnostic biomarker and therapeutic target of GBM.

Sign in / Sign up

Export Citation Format

Share Document