scholarly journals The long noncoding RNA KTN1-AS1 promotes bladder cancer tumorigenesis via KTN1 cis-activation and the consequent initiation of Rho GTPase-mediated signaling

2021 ◽  
Vol 135 (3) ◽  
pp. 555-574
Author(s):  
Xueying Hu ◽  
Liang Xiang ◽  
Dong He ◽  
Rongrong Zhu ◽  
Jianing Fang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Noncoding Rna ◽  
Rho Gtpase ◽  
Invasion And Migration ◽  
Rna Immunoprecipitation ◽  
And Migration ◽  
Epigenetic Modulation

Abstract Background: Accumulating evidence support the hypothesis that long noncoding RNAs (lncRNAs) are involved in several physiological and pathological conditions, including cancer. Here, we investigated the potential role of lncRNAs in bladder cancer. Methods: We first looked at available datasets retrieved from the TCGA database and discovered that the lncRNA KTN 1 antisense RNA 1 (KTN1-AS1) was significantly up-regulated in several cancer types including bladder cancer, but was decreased in some other tumors. Therefore, we focused our attention on KTN1-AS1. Using both in vitro and in vivo systems that allowed the modulation of KTN1-AS1 and expression of other relevant proteins, we investigated in-depth the role of KTN1-AS1 in bladder cancer (and the mechanism behind). We further investigated the potential KTN1-AS1-interacting proteins using RNA immunoprecipitation, and explored the KTN1-AS1-related epigenetic landscape (with a particular emphasis on acetylation) using chromatin immunoprecipitation (ChIP) assays. Results: KTN1-AS1 silencing inhibited the proliferation, invasion, and migration of bladder cancer cells, while KTN1-AS1 overexpression had the obvious opposite effects. Mechanistically, KTN1-AS1 promoted the recruitment of EP300, a histone acetyltransferase that enriched acetylation of histone H3 at lysine 27 (H3K27Ac) in the KTN1 promoter region. This epigenetic modulation contributed to the up-regulation of KTN1, which affected bladder cancer growth and progression via the regulation of Rho GTPase (RAC1, RHOA, and CDC42)-mediated signaling. Conclusion: Overall, our data support the idea that the lncRNA KTN1-AS1 promotes bladder cancer tumorigenesis via modulation of the KTN1/Rho GTPase axis and is a promising new therapeutic target for the treatment of bladder cancer.

scholarly journals Suppression of long noncoding RNA MALAT1 inhibits the development of uveal melanoma via microRNA-608-mediated inhibition of HOXC4

2020 ◽  
Vol 318 (5) ◽  
pp. C903-C912 ◽  
Author(s):  
Shuai Wu ◽  
Han Chen ◽  
Ling Zuo ◽  
Hai Jiang ◽  
Hongtao Yan
Keyword(s):  
Cell Cycle ◽  
Uveal Melanoma ◽  
Noncoding Rna ◽  
Cell Cycle Progression ◽  
Melanoma Cells ◽  
Cell Cycle Distribution ◽  
Invasion And Migration ◽  
And Migration

This study explored the effects of the metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on the development of uveal melanoma. Moreover, the role of the MALAT1/microRNA-608 (miR-608)/homeobox C4 (HOXC4) axis was assessed by evaluating the proliferation, invasion, and migration, as well as the cell cycle distribution of uveal melanoma in vitro after knocking down MALAT1 or HOXC4 and/or overexpression of miR-608 in uveal melanoma cells (MUM-2B and C918). Moreover, the effects of the MALAT1/miR-608/HOXC4 axis in uveal melanoma in vivo were further evaluated by injecting the C918 cells into the NOD/SCID mice. HOXC4 was found to be a gene upregulated in uveal melanoma, while knockdown of its expression resulted in suppression of uveal melanoma cell migration, proliferation, and invasion, as well as cell cycle progression. In addition, the upregulation of miR-608 reduced the expression of HOXC4 in the uveal melanoma cells, which was rescued by overexpression of MALAT1. Hence, MALAT1 could upregulate the HOXC4 by binding to miR-608. The suppressed progression of uveal melanoma in vitro by miR-608 was rescued by overexpression of MALAT1. Additionally, in vivo assays demonstrated that downregulation of MALAT1 could suppress tumor growth through downregulation of HOXC4 expression via increasing miR-608 in uveal melanoma. In summary, MALAT1 downregulation functions to restrain the development of uveal melanoma via miR-608-mediated inhibition of HOXC4.

scholarly journals microRNA-27b inhibits cell proliferation and invasion in bladder cancer by targeting engrailed-2

2020 ◽  
Author(s):  
Yunfei Li ◽  
Qilin Duan ◽  
Lu Gan ◽  
Wei Li ◽  
Jianggen Yang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Malignant Tumour ◽  
Expression Level ◽  
Luciferase Reporter ◽  
Reporter System ◽  
Invasion And Migration ◽  
Great Heterogeneity ◽  
And Migration

Background: Bladder cancer is considered a malignant tumour characterised by great heterogeneity. Engrailed-2 may be a gene implicated in bladder cancer. Bioinformatics analysis found base pair complementation between microRNA-27b and engrailed-2. This study aimed to investigate the reciprocal association between microRNA-27b and engrailed-2 in bladder cancer. Methods: The microRNA-27b and the proteins of engrailed-2 in the tissues and cells of the bladder were detected. The processes of apoptosis, proliferation, invasion, and migration of tumour cells were evaluated. The co-action between microRNA-27b and engrailed-2 was detected by a luciferase reporter system. Finally, the interaction between microRNA-27b and engrailed-2 was further verified in vivo. Results: The study found that the expression level of microRNA-27b is lower in bladder cancer tissues and cells than that in neighbouring ordinary tissues, whereas the opposite outcome was observed regarding the expression level of engrailed-2. Furthermore, microRNA-27b expression level is not significantly linked to the age of patients with bladder cancer; however, it is significantly associated with the clinicopathological grade of bladder cancer. Notably, engrailed-2 is negatively regulated by microRNA-27b. Transfection with microRNA-27b was associated with a significant reduction in the activity of bladder cancer cells and promoted apoptosis, while engrailed-2 restoration effectively reversed the above effects of microRNA-27b on bladder cancer in vitro and in vivo. Conclusions: In conclusion, engrailed-2 is engaged in the development and process of bladder cancer through the negative mediation of microRNA-27b; additionally, microRNA-27b/engrailed-2 could form a signalling pathway with a significant effect on the process of bladder cancer.

scholarly journals LncRNA SNHG20 promotes migration and invasion of ovarian cancer via modulating the microRNA-148a/ROCK1 axis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qi Yang ◽  
Yu-Jie Dong
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Noncoding Rna ◽  
Tumor Xenograft ◽  
Migration And Invasion ◽  
Epithelial Cell Line ◽  
Invasion And Migration ◽  
And Migration

Abstract Background Ovarian cancer (OC) is characterized by early metastasis and poor prognosis, which threatens the health of women worldwide. Small nucleolar RNA host gene 20 (SNHG20), a long noncoding RNA (lncRNA), has been verified to be significantly up-regulated in several tumors, including OC. MicroRNA-148a (miR-148a)/rho-kinase1 (ROCK1) axis plays an important role in the modulation of tumor development. However, whether SNHG20 can regulate OC progression through miR-148a/ROCK1 axis remains unclear. Normal human ovarian epithelial cell line and four OC cell lines were adopted for in vitro experiments. Real-time PCR was performed to assess the levels of SNHG20 and miR-148a. OC cell proliferation, apoptosis, invasion and migration were detected using clone formation, flow cytometry, transwell, and wound healing assays, respectively. Tumor xenograft assay was applied to evaluate the effect of SNHG20 on tumor growth in vivo. Results Significant higher expression of SNHG20 was observed in OC cell lines. SNHG20 markedly promoted the invasion, migration, proliferation and inhibited the apoptosis of OC cells. SNHG20 enhanced ROCK1 expression by sponging miR-148a, and the direct binding between SNHG20/ROCK1 and miR-148a was identified. Conclusion SNHG20 promoted invasion and migration of OC via targeting miR-148a/ROCK1 axis. The present research may provide a novel insight for the therapeutic strategies of OC.

scholarly journals lncRNA OXCT1-AS1 Promotes Metastasis in Non-Small-Cell Lung Cancer by Stabilizing LEF1, In Vitro and In Vivo

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Binru Li ◽  
Libo Zhu ◽  
Linlin Li ◽  
Rui Ma
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Small Cell ◽  
Small Cell Lung ◽  
Invasion And Migration ◽  
And Migration

Long noncoding RNAs (lncRNAs) play nonnegligible roles in the metastasis of non-small-cell lung cancer (NSCLC). This study is aimed at investigating the biological role of lncRNA OXCT1-AS1 in NSCLC metastasis and the underlying regulatory mechanisms. The expression profiles of lncRNA OXCT1-AS1 in different NSCLC cell lines were examined. Then, the biological function of lncRNA OXCT1-AS1 in NSCLC metastasis was explored by loss-of-function assays in vitro and in vivo. Further, the protective effect of lncRNA OXCT1-AS1 on lymphoid enhancer factor 1 (LEF1) was examined using RNA pull-down and RNA immunoprecipitation assays. Additionally, the role of LEF1 in NSCLC metastasis was investigated. Results indicated that lncRNA OXCT1-AS1 expression was significantly increased in NSCLC cell lines. Functional analysis revealed that knockdown of lncRNA OXCT1-AS1 impaired invasion and migration in vitro. Additionally, the ability of lncRNA OXCT1-AS1 to promote NSCLC metastasis was also confirmed in vivo. Mechanistically, through direct interaction, lncRNA OXCT1-AS1 maintained LEF1 stability by blocking NARF-mediated ubiquitination. Furthermore, LEF1 knockdown impaired invasion and migration of NSCLC in vitro and in vivo. Collectively, these data highlight the ability of lncRNA OXCT1-AS1 to promote NSCLC metastasis by stabilizing LEF1 and suggest that lncRNA OXCT1-AS1 represents a novel therapeutic target in NSCLC.

EBAG9 is a tumor‐promoting and prognostic factor for bladder cancer.

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Bladder Cancer ◽  
Immunohistochemical Study ◽  
Tumor Formation ◽  
Loss Of Function ◽  
Xenograft Models ◽  
Prostate Cancers ◽  
And Migration

Upregulation of EBAG9 expression has been observed in severalmalignant tumors such as advanced breast and prostate cancers,indicating that EBAG9 may contribute to tumor proliferation. Inthe present study, we assess the role of EBAG9 in bladder cancer.We generated human bladder cancer EJ cells stably expressingFLAG-tagged EBAG9 (EJ-EBAG9) or empty vector (EJ-vector),and investigated whether EBAG9 overexpression modulates cellgrowth and migration in vitro as well as the in vivo tumor formationof EJ transfectants in xenograft models of BALB/c nude mice.EBAG9 overexpression promoted EJ cell migration, while theeffect of EBAG9 to cultured cell growth was rather minimal.Tumorigenic experiments in nude mice showed that the size of EJEBAG9-derived tumors was significantly larger than EJ-vectorderivedtumors. Loss-of-function study for EBAG9 using smallinterfering RNA (siRNA) in xenografts with parental EJ cellsshowed that the intra-tumoral injection of EBAG9 siRNA markedlyreduced the EJ tumor formation compared with controlsiRNA. Furthermore, immunohistochemical study for EBAG9expression was performed in 60 pathological bladder cancer specimens.Intense and diffuse cytoplasmic immunostaining wasobserved in 45% of the bladder cancer cases. Positive EBAG9immunoreactivity was closely correlated with poor prognosis ofthe patients (p 5 0.0001) and it was an independent prognosticpredictor for disease-specific survival in multivariate analysis(p 5 0.003). Our results indicate that EBAG9 would be a crucialregulator of tumor progression and a potential prognostic markerfor bladder cancer.

MiR-134, Mediated by IRF1, Suppresses Tumorigenesis and Progression by Targeting VEGFA and MYCN in Osteosarcoma

2020 ◽  
Vol 20 (10) ◽  
pp. 1197-1208
Author(s):  
Zhuo Ma ◽  
Kai Li ◽  
Peng Chen ◽  
Qizheng Pan ◽  
Xuyang Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mrna Levels ◽  
Invasion And Migration ◽  
And Migration

Background: Osteosarcoma (OS) is a prevalent primary bone malignancy and its distal metastasis remains the main cause of mortality in OS patients. MicroRNAs (miRNAs) play critical roles during cancer metastasis. Objective: Thus, elucidating the role of miRNA dysregulation in OS metastasis may provide novel therapeutic targets. Methods: The previous study found a low miR-134 expression level in the OS specimens compared with paracancer tissues. Overexpression of miR-134 stable cell lines was established. Cell viability assay, cell invasion and migration assay and apoptosis assay were performed to evaluate the role of miR-134 in OS in vitro. Results: We found that miR-134 overexpression inhibits cell proliferation, migration and invasion, and induces cell apoptosis in both MG63 and Saos-2 cell lines. Mechanistically, miR-134 targets the 3'-UTR of VEGFA and MYCN mRNA to silence its translation, which was confirmed by luciferase-reporter assay. The real-time PCR analysis illustrated that miR-134 overexpression decreases VEGFA and MYCN mRNA levels. Additionally, the overexpression of VEGFA or MYCN can partly attenuate the effects of miR-134 on OS cell migration and viability. Furthermore, the overexpression of miR-134 dramatically inhibits tumor growth in the human OS cell line xenograft mouse model in vivo. Moreover, bioinformatic and luciferase assays indicate that the expression of miR-134 is regulated by Interferon Regulatory Factor (IRF1), which binds to its promoter and activates miR-134 expression. Conclusion: Our study demonstrates that IRF1 is a key player in the transcriptional control of miR-134, and it inhibits cell proliferation, invasion and migration in vitro and in vivo via targeting VEGFA and MYCN.

scholarly journals Nanaomycin K inhibited epithelial mesenchymal transition and tumor growth in bladder cancer cells in vitro and in vivo

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Koichi Kitagawa ◽  
Katsumi Shigemura ◽  
Aya Ishii ◽  
Takuji Nakashima ◽  
Hirotaka Matsuo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Invasion And Migration ◽  
Bladder Cancer Cells ◽  
And Migration ◽  
Muscle Invasive

AbstractNanaomycin K, derived from Streptomyces rosa subsp. notoensis OS-3966T, has been discovered to have inhibitory bioactivity on epithelial–mesenchymal transition (EMT), an important mechanism of cancer cell invasion and migration. In this study, we examined the anti-EMT and anti-tumor effect of nanaomycin K in bladder cancer, where EMT has important roles in progression. We treated two bladder cancer lines, non-muscle-invasive KK47 and muscle-invasive T24, with nanaomycin K to determine the effects on cell proliferation, apoptosis and expression of EMT markers in vitro. Wound-healing assays were performed to assess cell invasion and migration. We conducted an in vivo xenograft study in which mice were inoculated with bladder cancer cells and treated with intratumoral administration of nanaomycin K to investigate its anti-tumor and EMT inhibition effects. As the results, nanaomycin K (50 µg/mL) significantly inhibited cell proliferation in KK47 (p < 0.01) and T24 (p < 0.01) in the presence of TGF-β, which is an EMT-inducer. Nanaomycin K (50 µg/mL) also significantly inhibited cell migration in KK47 (p < 0.01) and T24 (p < 0.01), and induced apoptosis in both cell lines in the presence of TGF-β (p < 0.01). Nanaomycin K increased the expression of E-cadherin and inhibited the expression of N-cadherin and vimentin in both cell lines. Nanaomycin K also decreased expression of Snail, Slug, phospho-p38 and phospho-SAPK/JNK especially in T24. Intratumoral administration of nanaomycin K significantly inhibited tumor growth in both KK47 and T24 cells at high dose (1.0 mg/body) (p = 0.009 and p = 0.003, respectively) with no obvious adverse events. In addition, nanaomycin K reversed EMT and significantly inhibited the expression of Ki-67 especially in T24. In conclusion, we demonstrated that nanaomycin K had significant anti-EMT and anti-tumor effects in bladder cancer cells, suggesting that nanaomycin K may be a therapeutic candidate for bladder cancer treatment.

scholarly journals EGFR-AS1 Promotes Bladder Cancer Progression by Upregulating EGFR

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Anbang Wang ◽  
Aimin Jiang ◽  
Xinxin Gan ◽  
Zheng Wang ◽  
Jinming Huang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Progression ◽  
Noncoding Rna ◽  
Diagnostic Marker ◽  
Bladder Cancer Cells ◽  
The Relationship ◽  
Proliferation And Invasion

Long noncoding RNAs play an essential role in bladder cancer progression. The role of long noncoding RNA EGFR-AS1 in bladder cancer needs further study. We used clinical specimens to analyze the relationship between EGFR-AS1 and bladder cancer patients’ characteristics. The functional experiments and mechanism studies were performed using qRT-PCR, transwell assay, survival analysis, and correlation analysis. We found that high expression of EGFR-AS1 was nearly related to aggressive bladder cancer and indicated poor prognosis for patients. The functional experiments in vivo and in vitro suggested that EGFR-AS1 promoted the proliferation and invasion of bladder cancer cells. Mechanically, EGFR-AS1 promoted the expression of EGFR by inhibiting the degradation of EGFR mRNA, thereby promoting the metastasis of bladder cancer. In addition, EGFR-AS1/EGFR may be involved in the immune-related pathways of bladder cancer. These studies indicate that the EGFR-AS1/EGFR pathway may be a potential diagnostic marker and therapeutic target for bladder cancer.

scholarly journals Long noncoding RNA NEAT1 (nuclear paraspeckle assembly transcript 1) is critical for phenotypic switching of vascular smooth muscle cells

2018 ◽  
Vol 115 (37) ◽  
pp. E8660-E8667 ◽  
Author(s):  
Abu Shufian Ishtiaq Ahmed ◽  
Kunzhe Dong ◽  
Jinhua Liu ◽  
Tong Wen ◽  
Luyi Yu ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Phenotypic Switching ◽  
Specific Gene ◽  
Neointima Formation ◽  
Vsmc Proliferation ◽  
And Migration ◽  
Proliferation And Migration

In response to vascular injury, vascular smooth muscle cells (VSMCs) may switch from a contractile to a proliferative phenotype thereby contributing to neointima formation. Previous studies showed that the long noncoding RNA (lncRNA) NEAT1 is critical for paraspeckle formation and tumorigenesis by promoting cell proliferation and migration. However, the role of NEAT1 in VSMC phenotypic modulation is unknown. Herein we showed that NEAT1 expression was induced in VSMCs during phenotypic switching in vivo and in vitro. Silencing NEAT1 in VSMCs resulted in enhanced expression of SM-specific genes while attenuating VSMC proliferation and migration. Conversely, overexpression of NEAT1 in VSMCs had opposite effects. These in vitro findings were further supported by in vivo studies in which NEAT1 knockout mice exhibited significantly decreased neointima formation following vascular injury, due to attenuated VSMC proliferation. Mechanistic studies demonstrated that NEAT1 sequesters the key chromatin modifier WDR5 (WD Repeat Domain 5) from SM-specific gene loci, thereby initiating an epigenetic “off” state, resulting in down-regulation of SM-specific gene expression. Taken together, we demonstrated an unexpected role of the lncRNA NEAT1 in regulating phenotypic switching by repressing SM-contractile gene expression through an epigenetic regulatory mechanism. Our data suggest that NEAT1 is a therapeutic target for treating occlusive vascular diseases.

scholarly journals The Origin of Stroma Influences the Biological Characteristics of Oral Squamous Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3491
Author(s):  
Haruka Omori ◽  
Qiusheng Shan ◽  
Kiyofumi Takabatake ◽  
Keisuke Nakano ◽  
Hotaka Kawai ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Tartrate Resistant Acid Phosphatase ◽  
Bioinformatics Analyses ◽  
Invasion And Migration ◽  
Migration Assays ◽  
Tumor Parenchyma ◽  
And Migration

Normal stromal cells surrounding the tumor parenchyma, such as the extracellular matrix (ECM), normal fibroblasts, mesenchymal stromal cells, and osteoblasts, play a significant role in the progression of cancers. However, the role of gingival and periodontal ligament tissue-derived stromal cells in OSCC progression is unclear. In this study, the effect of G-SCs and P-SCs on the differentiation, proliferation, invasion, and migration of OSCC cells in vitro was examined by Giemsa staining, Immunofluorescence (IF), (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS), invasion, and migration assays. Furthermore, the effect of G-SCs and P-SCs on the differentiation, proliferation, and bone invasion by OSCC cells in vivo was examined by hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), and tartrate-resistant acid phosphatase (TRAP) staining, respectively. Finally, microarray data and bioinformatics analyses identified potential genes that caused the different effects of G-SCs and P-SCs on OSCC progression. The results showed that both G-SCs and P-SCs inhibited the differentiation and promoted the proliferation, invasion, and migration of OSCC in vitro and in vivo. In addition, genes, including CDK1, BUB1B, TOP2A, DLGAP5, BUB1, and CCNB2, are probably involved in causing the different effects of G-SCs and P-SCs on OSCC progression. Therefore, as a potential regulatory mechanism, both G-SCs and P-SCs can promote OSCC progression.

Sign in / Sign up

Export Citation Format

Share Document