scholarly journals Pseudogene OCT4-pg5 Upregulates OCT4B Expression To Promote Bladder Cancer Progression By Competing With miR-145

2021 ◽  
Author(s):  
Wuer Zhou ◽  
Yue Yang ◽  
Wei Wang ◽  
Chenglin Yang ◽  
Zhi Cao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Tumor Grade ◽  
Luciferase Reporter ◽  
In Vivo Experiments ◽  
Bladder Cell ◽  
Advanced Tumor

Abstract Background Octamer-binding transcription factor 4 pseudogene 5 (OCT4-pg5) contributes to tumor progression in many cancer types, but contributions to bladder cancer (BC) have not been investigated. Methods Real-time quantity PCR (RT-qPCR) was performed to measure OCT4-pg5 and OCT4B expressions in different bladder cell lines and different grades of cancer. The effects of OCT4-pg5, OCT4B and miR-145 on proliferation and metastasis were determined by in vitro and in vivo experiments. Luciferase reporter assay was carried out to reveal the interaction among OCT4-pg5, OCT4B and miR-145. Flow cytometry was performed to explore the effects of OCT4-pg5 and OCT4B expression on the cell cycle stage distribution of T24 cells. Results OCT4-pg5 expression was significantly increased in BC cell lines, which was correlated with OCT4B expression and advanced tumor grade. Overexpression of OCT4-pg5 and OCT4B promoted the proliferation and invasion of BC cells, while miR-145 suppressed these activities. Mechanically, OCT4-pg5 3’ untranslated region (3’UTR) competed for miR-145, thereby increasing OCT4B expression. In addition, OCT4-pg5 promoted EMT by activating the Wnt/β-catenin pathway and upregulating the expression levels of matrix metalloproteinases (MMPs) 2 and 9 as well as transcription factors zinc finger E-box binding homeobox (ZEB) 1 and 2. Furthermore, elevated expression of OCT4-pg5 and OCT4B reduced the sensitivity of BC cells to cisplatin by reducing apoptosis and increasing the proportion of cells in G1. Conclusions These findings indicate that OCT4-pg5/miR-145/OCT4B axis promotes the progression of BC by inducing EMT via Wnt/β-catenin pathway and enhances the cisplatin resistance. It could be prospect for the therapeutic approaches for BC.

scholarly journals Circular RNA circ-ZKSCAN1 inhibits bladder cancer progression through miR-1178-3p/p21 axis and acts as a prognostic factor of recurrence

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Junming Bi ◽  
Hongwei Liu ◽  
Wei Dong ◽  
Weibin Xie ◽  
Qingqing He ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Bladder Cancer ◽  
Cancer Progression ◽  
Tumor Grade ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Rank Test ◽  
Circular Rnas

Abstract Background Circular RNAs (circRNAs) represent a subclass of regulatory RNAs that have been shown to have significant regulatory roles in cancer progression. However, the biological functions of circRNAs in bladder cancer (BCa) are largely unknown. Methods Cell invasion models were established, and invasion-related circRNAs were detected by qPCR. Using above method, circ-ZKSCAN1 was picked out for further study. Circ-ZKSCAN1 expression and survival analyses were performed through qPCR. The survival curves were generated by the Kaplan-Meier method, and the log-rank test was used to assess the significance. Cell proliferation, migration and invasion were examined to investigate the function of circ-ZKSCAN1. Tumorigenesis in nude mice was assessed to determine the effect of circ-ZKSCAN1 in bladder cancer. Biotin-coupled probe pull-down assays, FISH and luciferase reporter assays were conducted to confirm the relationship between circ-ZKSCAN1 and microRNA. RNA-seq revealed different molecular changes in downstream genes. Results Here, we found that circ-ZKSCAN1 was downregulated in BCa tissues and cell lines. Circ-ZKSCAN1 levels were associated with survival, tumor grade, pathological T stage and tumor recurrence. Overexpressed circ-ZKSCAN1 inhibits cell proliferation, migration, invasion and metastasis in vitro and in vivo. Mechanistically, we demonstrated that circ-ZKSCAN1 upregulated p21 expression by sponging miR-1178-3p, which suppressed the aggressive biological behaviors in bladder cancer. Conclusions These results reveal that Circ-ZKSCAN1 acts as a tumor suppressor via a novel circ-ZKSCAN1/miR-1178-3p/p21 axis, which have the important role in the proliferation, migration and invasion ablitities of BCa cells and provide a novel perspective on circRNAs in BCa progression.

scholarly journals Impact of RARα and miR-138 on retinoblastoma etoposide resistance

Tumor Biology ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 11-26
Author(s):  
Maike Busch ◽  
Natalia Miroschnikov ◽  
Jaroslaw Thomas Dankert ◽  
Marc Wiesehöfer ◽  
Klaus Metz ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Lines ◽  
Cancer Progression ◽  
Treated Patient ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Gene Assay ◽  
The Impact

BACKGROUND: Retinoblastoma (RB) is the most common childhood eye cancer. Chemotherapeutic drugs such as etoposide used in RB treatment often cause massive side effects and acquired drug resistances. Dysregulated genes and miRNAs have a large impact on cancer progression and development of chemotherapy resistances. OBJECTIVE: This study was designed to investigate the involvement of retinoic acid receptor alpha (RARα) in RB progression and chemoresistance as well as the impact of miR-138, a potential RARα regulating miRNA. METHODS: RARα and miR-138 expression in etoposide resistant RB cell lines and chemotherapy treated patient tumors compared to non-treated tumors was revealed by Real-Time PCR. Overexpression approaches were performed to analyze the effects of RARα on RB cell viability, apoptosis, proliferation and tumorigenesis. Besides, we addressed the effect of miR-138 overexpression on RB cell chemotherapy resistance. RESULTS: A binding between miR-138 and RARα was shown by dual luciferase reporter gene assay. The study presented revealed that RARα is downregulated in etoposide resistant RB cells, while miR-138 is endogenously upregulated. Opposing RARα and miR-138 expression levels were detectable in chemotherapy pre-treated compared to non-treated RB tumor specimen. Overexpression of RARα increases apoptosis levels and reduces tumor cell growth of aggressive etoposide resistant RB cells in vitro and in vivo. Overexpression of miR-138 in chemo-sensitive RB cell lines partly enhances cell viability after etoposide treatment. CONCLUSIONS: Our findings show that RARα acts as a tumor suppressor in retinoblastoma and is downregulated upon etoposide resistance in RB cells. Thus, RARα may contribute to the development and progression of RB chemo-resistance.

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.

scholarly journals MiR-203 Determines Poor Outcome and Suppresses Tumor Growth by Targeting TBK1 in Osteosarcoma

2015 ◽  
Vol 37 (5) ◽  
pp. 1956-1966 ◽  
Author(s):  
Shiping Liu ◽  
Peng Feng
Keyword(s):  
Cell Growth ◽  
Cell Lines ◽  
Cancer Progression ◽  
Human Cancer ◽  
Luciferase Reporter ◽  
Luciferase Reporter Gene ◽  
Poor Overall Survival ◽  
Gene Assay

Background/Aims: Increasing evidence has shown that miR-203 plays important role in human cancer progression. However, little is known about the function of miR-203 in osteosarcoma (OS). Methods: The expression of miR-203 in OS tissues and cell lines were examined by qRT-PCR. The biological role of miR-20 in OS cell proliferation was examined in vitro and in vivo. The targets of miR-203 were identified by a luciferase reporter gene assay. Results: miR-203 was down regulated in OS tissues and cell lines; decreased miR-203 was associated with a poor overall survival in OS patients. Restoration of miR-203 expression reduced cell growth in vitro and suppressed tumorigenicity in vivo. In contrast, inhibition of miR-203 stimulated OS cell growth both in vitro and in vivo. In addition, TANK binding kinase 1 (TBK1) was identified as a direct target of miR-203; overexpression of TBK1 partly reversed the suppressive effects of miR-203. Furthermore, TBK1 was found up-regulated and inversely correlated with miR-203 in OS tissues. Conclusion: Taken together, these findings suggest that miR-203 acts as a tumor suppressor via regulation of TBK1 expression in OS progression, and miR-203 may be a promising therapeutic target for OS.

scholarly journals CircZNF609 Promotes Bladder Cancer Progression and Inhibits Cisplatin Sensitivity via miR-1200/CDC25B Pathway

2021 ◽  
Author(s):  
Dexiang Feng ◽  
Jiancheng Lv ◽  
Kai Li ◽  
Qiang Cao ◽  
Jie Han ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Tumor Development ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Online Databases ◽  
Cisplatin Sensitivity ◽  
Cisplatin Chemoresistance

Abstract Circular RNAs (circRNAs) have been extensively studied in tumor development and treatment. CircZNF609 has been shown to act as an oncogene in a variety of solid tumors and may serve as a novel biomarker for tumor diagnosis and treatment. However, the underlying role and mechanism of circZNF609 in bladder cancer (BCa) development and cisplatin chemosensitivity were unknown. Quantitative real-time PCR (qRT-PCR) was applied to determine the expression of circZNF609, microRNA 1200 (miR-1200) and CDC25B in BCa cells and tissues. Western blot was used to detect the protein level of CDC25B. Functional assays in vitro and in vivo were conducted to investigate the effects of circZNF609 on tumor development and cisplatin chemosensitivity in BCa. RNA sequencing and online databases were used to predict the interactions among circZNF609, miR-1200 and CDC25B. Dual luciferase reporter assay, RNA pull-down assay and RNA fluorescence in situ hybridization (FISH) were applied to confirm the mechanism. CircZNF609 expression was significantly up-regulated in BCa cell lines and tissues. Increased expression of circZNF609 was related to a worse survival in BCa patients. In vitro and in vivo, enforced-expression of circZNF609 enhanced BCa cells proliferation, migration and cisplatin chemoresistance. Mechanistically, circZNF609 alleviated the inhibition effect on target CDC25B expression by sponging miR-1200. CircZNF609 promoted tumor growth through novel circZNF609/miR-1200/CDC25B axis, implying that circZNF609 has significant potential to serve as a new diagnostic biomarker and therapeutic target for BCa patients.

scholarly journals TSPAN7 Exerts Anti-Tumor Effects in Bladder Cancer Through the PTEN/PI3K/AKT Pathway

2021 ◽  
Vol 10 ◽  
Author(s):  
Xi Yu ◽  
Shenglan Li ◽  
Mingrui Pang ◽  
Yang Du ◽  
Tao Xu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Lines ◽  
Therapeutic Potential ◽  
Tumor Grade ◽  
Biological Properties ◽  
Akt Pathway ◽  
Dynamic Regulation ◽  
Potential Marker

The tetraspanin protein superfamily participate in the dynamic regulation of cellular membrane compartments expressed in a variety of tumor types, which may alter the biological properties of cancer cells such as cell development, activation, growth and motility. The role of tetraspanin 7 (TSPAN7) has never been investigated in bladder cancer (BCa). In this study, we aimed to investigate the biological function of TSPAN7 and its therapeutic potential in human BCa. First, via reverse transcription and quantitative real-time PCR (qRT-PCR), we observed downregulation of TSPAN7 in BCa tissues samples and cell lines and found that this downregulation was associated with a relatively high tumor stage and tumor grade. Low expression of TSPAN7 was significantly correlated with a much poorer prognosis for BCa patients than was high expression. Immunohistochemistry (IHC) showed that low TSPAN7 expression was a high-risk predictor of BCa patient overall survival. Furthermore, the inhibitory effects of TSPAN7 on the proliferation and migration of BCa cell lines were detected by CCK-8, wound-healing, colony formation and transwell assays in vitro. Flow cytometry analysis revealed that TSPAN7 induced BCa cell lines apoptosis and cell cycle arrest. In vivo, tumor growth in nude mice bearing tumor xenografts could be obviously affected by overexpression of TSPAN7. Western blotting showed that overexpression of TSPAN7 activated Bax, cleaved caspase-3 and PTEN but inactivated Bcl-2, p-PI3K, and p-AKT to inhibit BCa cell growth via the PTEN/PI3K/AKT pathway. Taken together, our study will help identify a potential marker for BCa diagnosis and supply a target molecule for BCa treatment.

scholarly journals Linc00473 potentiates cholangiocarcinoma progression by modulation of DDX5 expression via miR-506 regulation

2020 ◽  
Author(s):  
Lining Huang ◽  
Xingming Jiang ◽  
Zhenglong Li ◽  
Jinglin Li ◽  
Xuan Lin ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Qrt Pcr ◽  
Competitive Endogenous Rnas ◽  
Rna Immunoprecipitation ◽  
Underlying Mechanisms

Abstract Background: Cholangiocarcinoma (CCA) is a mortal cancer with high mortality, whereas the function and mechanism of occurrence and progression of CCA are still mysterious. Long non-coding RNAs (lncRNAs) could function as important regulators in carcinogenesis and cancer progression. Growing evidences have indicated that the novel lncRNA linc00473 plays an important role in cancer progression and metastasis. However, its function and molecular mechanism in CCA remain unknown. Methods: The linc00473 expression in CCA tissues and cell lines was analyzed using qRT-PCR. Gain- and loss-of-function experiments were conducted to investigate the biological functions of linc00473 both in vitro and in vivo. Insights into the underlying mechanisms of competitive endogenous RNAs (ceRNAs) were determined by bioinformatics analysis, dual-luciferase reporter assays, qRT-PCR arrays, RNA immunoprecipitation (RIP) and rescue experiments. Results: Linc00473 was highly expressed in CCA tissues and cell lines. Linc00473 knockdown inhibited CCA growth and metastasis. Furthermore, linc00473 acted as miR-506 sponge and regulated its target gene DDX5 expression. Rescue assays verified that linc00473 modulated the tumorigenesis of CCA by regulating miR-506. Conclusions: The data indicated that linc00473 played an oncogenic role in CCA growth and metastasis, and could serve as a novel molecular target for treating CCA.

scholarly journals The novel circ_0028171/miR-218-5p/IKBKB axis promotes osteosarcoma cancer progression

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Feng Pan ◽  
Jun Zhang ◽  
Benseng Tang ◽  
Li Jing ◽  
Bing Qiu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Progression ◽  
Bone Cells ◽  
Human Cancer ◽  
Underlying Mechanism ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion

Abstract Background Recently, it has been demonstrated that circular RNA (circRNA) contributes to the production and progression in human cancer. However, the specific function and underlying mechanism of circ_0028171 in osteosarcoma (OS) still remain largely unclear and require to be investigated. Methods In our study, we confirmed differentially expressed circRNAs by microarray analysis in normal bone cells vs. OS cell lines. The expression of circ-0028171 in OS was measured by qRT-PCR. Nuclear-cytoplasmic fractionation was employed to identify the localization of circ-0028171, and RNase R and actinomycin D treatment were used to prove its circular characteristic. In vitro experiments, such as CCK-8 method, cell count, cell colony formation, transwell migration and invasion assays, and in vivo tumor models were adopted to evaluate the effect of circ_0028171. Further, luciferase reporter, RIP and RNA pull-down assays were conducted to confirm the binding sites of circ_0028171 with miR-218-5p. Results We found that circ_0028171 displayed a remarkably higher expression in both OS tissues and cell lines. Circ_0028171 mainly located in the cytoplasm as a stable cyclic transcript. Knockdown of circ_0028171 suppressed OS tumor growth in vitro and in vivo, while up-regulated circ_0028171 remarkably enhanced cell proliferation, migration and invasion abilities in OS. Several mechanistic experiments revealed that circ_0028171 served as a sponge of miR-218-5p to increase IKBKB expression. Conclusions our research reveals that circ_0028171 might promote the malignant behavior of OS tissues through miR-218-5p/IKBKB axis, which could be a potential novel marker for early diagnosis of OS.

scholarly journals circRIP2 accelerates bladder cancer progression via miR-1305/Tgf-β2/smad3 pathway

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Yinjie Su ◽  
Weilian Feng ◽  
Juanyi Shi ◽  
Luping Chen ◽  
Jian Huang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Rna Sequencing ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Sequencing Analysis ◽  
Potential Biomarker

Abstract Background Increasing evidences indicate that circular RNAs exert critical function in regulating bladder cancer progression. However, the expressive patterns and roles of circular RNAs in bladder cancer remain less investigated. Methods circRIP2 was identified and evaluated by RNA-sequencing and qPCR; in vitro effects of circRIP2 were determined by CCK8, clone forming, wound healing and trans-well assays; while mice subcutaneous tumor model was designed for in vivo analysis. Western blot, RNA pulldown assay, miRNA capture and dual luciferase assessment were applied for mechanistic studies. Results circRIP2 was identified as a conserved and dramatically repressed circular RNA in bladder cancer. Patients that displayed higher circRIP2 expression negatively associate with the grade, stage, metastasis as well as outcome of bladder cancer. In vitro and in vivo studies suggest that circRIP2 enables to promote bladder cancer progression via inducing EMT. Regarding the mechanism, we performed RNA-sequencing analysis, RNA pulldown with biotin-labeled circRIP2-specific probe, dual luciferase reporter assay. It was found that circRIP2 enables to sponge miR-1305 to elevate Tgf-β2 in bladder cancer, and inducing EMT via Tgf-β2/smad3 pathway. Blocking Tgf-β2 in bladder cancer deprives circRIP2 induced cancer progression and EMT. Conclusions Taken together, our study provides the first evidence that circRIP2 expresses differentially in bladder cancer and negatively along with the cancer progression; effective circRIP2 activity accelerates bladder cancer progression via inducing EMT by activating miR-1305/Tgf-β2/smad3 pathway. The research implies that circRIP2 might be a potential biomarker and therapeutic target for bladder cancer patients.

scholarly journals Linc00473 potentiates cholangiocarcinoma progression by modulation of DDX5 expression via miR-506 regulation

2020 ◽  
Author(s):  
Lining Huang ◽  
Xingming Jiang ◽  
Zhenglong Li ◽  
Jinglin Li ◽  
Xuan Lin ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Progression ◽  
Luciferase Reporter ◽  
Loss Of Function ◽  
Qrt Pcr ◽  
Competitive Endogenous Rnas ◽  
Rna Immunoprecipitation ◽  
Underlying Mechanisms

Abstract Background Cholangiocarcinoma (CCA) is a mortal cancer with high mortality, whereas the function and mechanism of occurrence and progression of CCA are still mysterious. Long non-coding RNAs (lncRNAs) could function as important regulators in carcinogenesis and cancer progression. Growing evidences have indicated that the novel lncRNA linc00473 plays an important role in cancer progression and metastasis. However, its function and molecular mechanism in CCA remain unknown. Methods The linc00473 expression in CCA tissues and cell lines was analyzed using qRT-PCR. Gain- and loss-of-function experiments were conducted to investigate the biological functions of linc00473 both in vitro and in vivo. Insights into the underlying mechanisms of competitive endogenous RNAs (ceRNAs) were determined by bioinformatics analysis, dual-luciferase reporter assays, qRT-PCR arrays, RNA immunoprecipitation (RIP) and rescue experiments. Results Linc00473 was highly expressed in CCA tissues and cell lines. Linc00473 knockdown inhibited CCA growth and metastasis. Furthermore, linc00473 acted as miR-506 sponge and regulated its target gene DDX5 expression. Rescue assays verified that linc00473 modulated the tumorigenesis of CCA by regulating miR-506. Conclusions The data indicated that linc00473 played an oncogenic role in CCA growth and metastasis, and could serve as a novel molecular target for treating CCA.

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