scholarly journals Long Non-Coding RNA HAGLROS Promotes the Malignant Progression of Bladder Cancer by Regulating the miR-330-5p/SPRR1B Axis

2022 ◽  
Author(s):  
Shiwei Xiao ◽  
Yigang Zuo ◽  
Yanan Li ◽  
Yinglong Huang ◽  
Shi Fu ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Molecular Mechanisms ◽  
Subcellular Fractionation ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Sequencing Analysis ◽  
Loss Of Function ◽  
Invasion And Migration ◽  
Potential Biomarker ◽  
Underlying Mechanisms

Abstract BackgroundBladder cancer (BC) is the most common genitourinary malignancy worldwide, and its aetiology and pathogenesis remain unclear. Long noncoding RNAs can play vital roles in gene expression and diverse biological processes, especially in cancers. Accumulating evidence has shown that HAGLROS, a novel lncRNA, is closely related to the occurrence and progression of various cancers. However, the biological functions and underlying mechanisms of HAGLROS in BC remain unknown.MethodsThe relative expression of HAGLROS in BC was determined by bioinformatics analysis, transcriptome sequencing analysis and qRT–PCR. Gain- or loss-of-function assays were performed to study the biological roles of HAGLROS in BC. A CCK-8 assay was used to detect BC cell proliferation. BC cell invasion and migration were investigated by wound healing and Transwell assays. The cell cycle was analysed by flow cytometry assay. Western blot analysis and immunohistochemistry were performed to evaluate SPRR1B expression. The differential expression of candidate genes and their relationships were evaluated in data retrieved from the starBase database, the GEIPIA database, the Lnc2Cancer database and the LncBase database. FISH assays, subcellular fractionation assays and luciferase reporter assays were performed to explore the underlying molecular mechanisms of HAGLROS.ResultsHAGLROS expression is significantly upregulated in BC tissues and cells, and increasing HAGLROS expression was related to high pathologic grade. HAGLROS enhances the proliferation, migration and invasion of BC. Furthermore, SPRR1B is obviously upregulated and miR-330-5p is significantly downregulated in BC. Mechanistically, we found that HAGLROS is mainly located in the cytoplasm and positively regulates SPRR1B expression by sponging miR-330-5p, playing an oncogenic role in BC pathogenesis.ConclusionsThe present study demonstrates that HAGLROS is significantly overexpressed and plays an oncogenic role by regulating the miR-330-5p/SPRR1B axis in BC. HAGLROS may serve as a potential biomarker for the diagnosis and treatment of BC.

scholarly journals MicroRNA-140-5p Inhibits the Progression of Colorectal Cancer by Targeting VEGFA

2015 ◽  
Vol 37 (3) ◽  
pp. 1123-1133 ◽  
Author(s):  
Wenbo Zhang ◽  
Chen Zou ◽  
Lei Pan ◽  
Ying Xu ◽  
Weidong Qi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Integrated Analysis ◽  
Loss Of Function ◽  
Invasion And Migration ◽  
Tumorigenesis And Progression

Background: microRNAs (miRNAs) are small non-coding RNAs and have been shown to play a crucial role in the colorectal cancer (CRC) tumorigenesis and progression. The aim of this study was to investigate the clinical significance and prognostic value of miR-140-5p in CRC. The exact functions and the underlying molecular mechanisms of miR-140-5p in CRC was further determined. Methods: miR-140-5p expression was detected in CRC samples, their adjacent nontumor tissues as well as CRC cell lines by RT-qPCR. Cell proliferation was detected using CCK-8, and cell invasion and migration were evaluated using Transwell assay. The direct regulation of VEGFA by miR-140-5p was identified using luciferase reporter assay. Results: miR-140-5p was significantly dowregulated in CRC tissues and cell lines. Downregulation of miR-140-5p was significantly correlated with advanced CRC stage and poorer overall survival. Both gain-of-function and loss of function studies demonstrated that miR-140-5p acted as a tumor suppressor by inhibiting cell proliferation, migration and invasion. Integrated analysis identified VEGFA as a direct and functional target gene of miR-140-5p. Silencing VEGFA by small interfering RNA (siRNA) resembled the phenotype resulting from ectopic miR-140-5p expression, while overexpression of VEGFA attenuated the effect of miR-140-5p on CRC cells. Conclusions: Our results suggested a tumor suppressive role of miR-140-5p in CRC tumorigenesis and progression by targeting VEGFA.

scholarly journals Long noncoding RNA SNHG25 promotes the malignancy of endometrial cancer by sponging microRNA-497-5p and increasing FASN expression

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yuhua He ◽  
Shuifang Xu ◽  
Yi Qi ◽  
Jinfang Tian ◽  
Fengying Xu
Keyword(s):  
Endometrial Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Fatty Acid Synthase ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Study Cohort ◽  
Loss Of Function ◽  
Ec Cells

Abstract Background Small nucleolar RNA host gene 25 (SNHG25), a long noncoding RNA, has been well-studied in epithelial ovarian cancer. However, the specific functions of SNHG25 in endometrial cancer (EC) have not been studied yet. In this study, we aimed to elucidate the clinical significance of SNHG25 in EC and determine the regulatory activity of SNHG25 on the tumor-associated EC phenotype. We also thoroughly explored the molecular mechanisms underlying SNHG25 function in EC. Methods Gene expression was measured using quantitative real-time polymerase chain reaction. The detailed functions of SNHG25 in EC were examined by performing loss-of-function experiments. Moreover, the regulatory mechanisms involving SNHG25, microRNA-497-5p, and fatty acid synthase (FASN) were unveiled using the luciferase reporter assay and RNA immunoprecipitation. Results We observed a high level of SNHG25 in EC using the TCGA dataset and our study cohort. Patients with a high SNHG25 level had shorter overall survival than those with a low SNHG25 level. SNHG25 deficiency resulted in tumor-repressing activities in EC cells by decreasing cell proliferation, migration, and invasion and promoting cell apoptosis. Furthermore, the function of SNHG25 depletion in impairing tumor growth in vivo was confirmed. SNHG25 sequestered miR-497-5p as a competing endogenous RNA in EC and consequently positively regulated FASN expression. Thus, the decrease in miR-497-5p or increase in FASN could neutralize the modulatory actions of SNHG25 knockdown in EC cells. Conclusions The depletion of SNHG25 impedes the oncogenicity of EC by targeting the miR-497-5p/FASN axis. The newly elucidated SNHG25/miR-497-5p/FASN pathway may be a promising target for the molecular-targeted management of EC.

scholarly journals Interference with NTSR1 Expression Exerts an Anti-Invasion Effect via the Jun/miR-494/SOCS6 Axis of Glioblastoma Cells

2018 ◽  
Vol 49 (6) ◽  
pp. 2382-2395 ◽  
Author(s):  
Qing Ou-yang ◽  
Xuzhi He ◽  
Anqi Yang ◽  
Bing Li ◽  
Minhui Xu
Keyword(s):  
Western Blotting ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Cytokine Signaling ◽  
Glioblastoma Cells ◽  
Suppressor Of Cytokine Signaling ◽  
Underlying Mechanisms ◽  
Neurotensin Receptor 1

Background/Aims: Glioblastoma is the most common and aggressive brain tumor and carries a poor prognosis. Previously, we found that neurotensin receptor 1 (NTSR1) contributes to glioma progression, but the underlying mechanisms of NTSR1 in glioblastoma invasion remain to be clarified. The aim of this study was to investigate the molecular mechanisms of NTSR1 in glioblastoma invasion. Methods: Cell migration and invasion were evaluated using wound-healing and transwell assays. Cell proliferation was detected using CCK-8. The expression of NTSR1, Jun, and suppressor of cytokine signaling 6 (SOCS6) was detected using western blotting. The expression of miR-494 was detected by Quantitative real-time PCR. Chromatin immunoprecipitation assay was performed to examine the interaction between Jun and miR-494 promoter. Dual-luciferase reporter assay and western blotting were performed to identify the direct regulation of SOCS6 by miR-494. An orthotopic xenograft mouse model was conducted to assess tumor growth and invasion. Results: NTSR1 knockdown attenuated the invasion of glioblastoma cells. Jun was positively regulated by NTSR1, which promoted miR-494 expression through binding to miR-494 promoter. SOCS6 was confirmed as a direct target of miR-494, thus, NTSR1-induced miR-494 upregulation resulted in SOCS6 downregulation. Both miR-494 and SOCS6 were involved in the NTSR1-induced invasion of glioblastoma cells. In vivo, tumor invasion and growth were inhibited by NTSR1 knockdown, but were restored with miR-494 overexpression. Conclusion: NTSR1 knockdown inhibited glioblastoma invasion via the Jun/miR-494/SOCS6 axis.

scholarly journals High TRAF6 Expression Is Associated With Esophageal Carcinoma Recurrence and Prompts Cancer Cell Invasion

2017 ◽  
Vol 25 (4) ◽  
pp. 485-493 ◽  
Author(s):  
Xinyang Liu ◽  
Zhichao Wang ◽  
Guoliang Zhang ◽  
Qikun Zhu ◽  
Hui Zeng ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Progression ◽  
Poor Prognosis ◽  
Molecular Mechanisms ◽  
Tumor Necrosis Factor Receptor ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Underlying Mechanisms ◽  
Patient Prognosis ◽  
Cancer Tissues

Esophageal cancer is one of the most common types of cancer, and it has a poor prognosis. The molecular mechanisms of esophageal cancer progression remain largely unknown. In this study, we aimed to investigate the clinical significance and biological function of tumor necrosis factor receptor-associated factor 6 (TRAF6) in esophageal cancer. Expression of TRAF6 in esophageal cancer was examined, and its correlation with clinicopathological factors and patient prognosis was analyzed. A series of functional and mechanism assays were performed to further investigate the function and underlying mechanisms in esophageal cancer. Expression of TRAF6 was highly elevated in esophageal cancer tissues, and patients with high TRAF6 expression have a significantly shorter survival time than those with low TRAF6 expression. Furthermore, loss-of-function experiments showed that knockdown of TRAF6 significantly reduced the migration and invasion abilities of esophageal cancer cells. Moreover, the pro-oncogenic effects of TRAF6 in esophageal cancer were mediated by the upregulation of AEP and MMP2. Altogether, our data suggest that high expression of TRAF6 is significant for esophageal cancer progression, and TRAF6 indicates poor prognosis in esophageal cancer patients, which might be a novel prognostic biomarker or potential therapeutic target in esophageal cancer.

scholarly journals MiR-219-5p is Involved in the Proliferation, Migration and Invasion of Oral Cancer Through SOX5 Regulation

2021 ◽  
Author(s):  
Ting Zhou ◽  
Ying He ◽  
Xiao-Han Dong ◽  
Bo Chen ◽  
Jun Ton ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Survival Rates ◽  
Luciferase Assay ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Rapid Progression ◽  
Invasion And Migration ◽  
Oral Cancer Cells

Abstract Purpose Oral cancer has the characteristics of rapid progression, wide invasion and poor prognosis, which induces higher mortality in the patients. At present, there are about 300 thousand new cases of oral cell carcinoma worldwide. Particularly, the incidence rate of oral cancer in China is relatively high. Therefore, it urgently needs to understand the pathogenesis of oral cancer and molecular mechanisms underlying. Abnormal regulation of miR-219-5p is present in various types of cancer. However, the relationship between miR-219-5p and its targets in oral cancer has not been well evaluated. Methods Western blotting and Quantitative RT-PCR were used to detect the expression of SOX5 in oral cancer tissues.Migration ,cell proliferation,and invasion were detected using CCK8 assay,Conlony formation assay and Transwell assays .The interaction between SOX5 and miR-219-5p and oral cancer was confirmed using dual-luciferase reporter assays.Result This study aims to investigate the possible roles of miR-219-5p and its potential target gene, SOX5, in the progress of oral cancer. Our data showed that the high miR-219-5p and low SOX5 expression levels were associated with improved survival rates in patients. miR-219-5p level was negatively correlated with the expression of SOX5. Genetic analysis and luciferase assay revealed that the miR-291-5p regulated SOX5 expression by targeting the 3'-UTR region of SOX5 mRNA. Functionally, we confirmed that miR-219-5p mimics inhibited SOX5 expression and suppressed the proliferation, colony formation ability, invasion and migration of oral cancer cells, SCC4 and SCC9. In contrast, inhibition of miR-219-5p increased SOX5 levels and promoted the vitality and mobility of oral cancer cells. Furthermore, special siRNA targeting SOX5 partially neutralized the effects of miR-219-5p inhibitor. Conclusions This study demonstrates that miR-219-5p may inhibit the proliferation, migration and invasion of oral cancer by targeting the expression of SOX5, which provided novel candidates for clinic prognosis and/or therapy.

scholarly journals miR-183-5p suppressed the invasion and migration of HTR-8/SVneo trophoblast cells partly via targeting MMP-9 in preeclampsia

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Mingli Suo ◽  
Yanfei Sun ◽  
Hailan Yang ◽  
Jing Ji ◽  
Yinfang He ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Cell Invasion ◽  
Underlying Mechanism ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Trophoblast Cells ◽  
Down Regulation ◽  
Invasion And Migration ◽  
Potential Biomarker ◽  
And Migration

Abstract Preeclampsia (PE), a common obstetrical disorder, is characterized by impaired migration and invasion abilities of trophoblastic cells. MicroRNA-183-5p (miR-183) was reported to regulate cell migration and invasion in various types of human cancers; however, its role in the pathogenesis of PE remains elusive. Herein, we investigated the role of miR-183 in HTR-8/SVneo trophoblast cells invasion and migration and explored the underlying mechanism. Our results showed that miR-183 was significantly up-regulated in placental tissues from pregnant women compared with that in normal pregnant women. Overexpression of miR-183 inhibited proliferation, migration and invasion, as well as induced apoptosis in HTR-8/SVneo cells. Otherwise, down-regulation of miR-183 achieved the opposite effects. Bioinformatics prediction and luciferase reporter assay confirmed that matrix metalloproteinase-9 (MMP-9) is a target of miR-183. In addition, MMP-9 expression was significantly down-regulated, and inversely correlated with the miR-183 level in placental tissues from pregnant women with severe PE. Down-regulation of MMP-9 suppressed the trophoblast cell invasion and migration, whereas overexpression of MMP-9 promoted cell invasion and migration in HTR-8/SVneo cells. More importantly, up-regulation of MMP-9 reversed the inhibitory effects of miR-183 on cell invasion and migration in trophoblast cells. Collectively, our findings suggested that miR-183 may play critical roles in the pathogenesis of PE and serve as a potential biomarker for severe PE.

scholarly journals The Long Non-coding RNA TMPO-AS1  Promotes Bladder Cancer Growth and Progression via OTUB1-induced E2F1 Deubiquitination

2020 ◽  
Author(s):  
Yeyu Zhang ◽  
Yuxing Zhu ◽  
Mengqing Xiao ◽  
Yaxin Cheng ◽  
Dong He ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
E2f Transcription Factor ◽  
Rna Immunoprecipitation ◽  
Regulatory Loop

Abstract BackgroundBladder cancer (BC) is the most common malignant tumor of the urinary system. Increasing evidence indicates long non-coding RNAs (lncRNAs) play crucial roles in cancer tumorigenesis, development, and progression. However, the role of TMPO antisense RNA 1 (TMPO-AS1) is still need to be explored in BC.MethodsThe lncRNA TMPO-AS1 expression was evaluated by bioinformatics analysis and further validated by qRT-PCR. Loss- and gain-of- function assays were performed to determine the biological functions of TMPO-AS1 in BC proliferation, migration, and invasion. Chromatin immunoprecipitation, luciferase reporter assays, western blotting, RNA pull-down, RNA immunoprecipitation assays, and fluorescence in situ hybridization were conducted to explore the molecular mechanisms of TMPO-AS1/E2F transcription factor 1 (E2F1) loop. ResultsTMPO-AS1 is upregulated in bladder cancer and is associated with BC patients’ poor prognoses. Functional experiments demonstrated that TMPO-AS1 promotes bladder cancer cell proliferation, migration, invasion, and inhibits cell apoptosis in vivo and in vitro. Mechanically, E2F1 is responsible for the TMPO-AS1 upregulation. Additionally, TMPO-AS1 facilitates the interaction of E2F1 with OTU domain-containing ubiquitin aldehyde binding 1 (OTUB1), leading to E2F1 deubiquitination and stabilization, thereby promotes BC malignant phenotypes. Furthermore, rescue experiments showed that TMPO-AS1 promotes BC growth in an E2F1-dependent manner.ConclusionsOur study is the first to uncover a novel positive regulatory loop of TMPO-AS1/E2F1 important for the promotion of BC malignant behaviors. The TMPO-AS1/E2F1 loop should be considered in the quest for new BC therapeutic options.

scholarly journals LncRNA RP11-89 facilitates tumorigenesis and ferroptosis resistance through PROM2-activated iron export by sponging miR-129-5p in bladder cancer

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Wenjie Luo ◽  
Jun Wang ◽  
Wenhao Xu ◽  
Chunguang Ma ◽  
Fangning Wan ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Molecular Mechanisms ◽  
Luciferase Reporter ◽  
Cycle Arrest ◽  
Potential Biomarker ◽  
Bladder Cancer Cells ◽  
Non Coding Rnas ◽  
Scratch Tests ◽  
Rip Assay ◽  
Iron Export

AbstractLong non-coding RNAs (lncRNAs) act as important regulators of tumorigenesis and development in bladder cancer. However, the underlying molecular mechanisms remain elusive. We previously identified a novel lncRNA signature related to immunity and progression in bladder cancer. Here we further explored the function of RP11-89, a lncRNA discovered in the previous signature. Loss- and gain-of function experiments were performed using CCK-8 assay, flow cytometry, Transwell assays, scratch tests and subcutaneous nude mouse models. High-throughput RNA sequencing was conducted to identify dysregulated genes in bladder cancer cells with RP11-89 knockdown or overexpression. Regulation of RP11-89 on miR-129-5p and PROM2 was explored through luciferase reporter assay, RIP assay and RNA pull-down assay. RP11-89 promoted cell proliferation, migration and tumorigenesis and inhibited cell cycle arrest via the miR-129-5p/PROM2 axis. We found that RP11-89 “sponges” miR-129-5p and upregulates PROM2. Elevated PROM2 in cells was associated with attenuated ferroptosis through iron export, formation of multivesicular bodies and less mitochondrial abnormalities. We demonstrated that RP11-89 is a novel tumorigenic regulator that inhibits ferroptosis via PROM2-activated iron export. RP11-89 may serve as a potential biomarker for targeted therapy in bladder cancer.

scholarly journals MiR-454-3p and miR-374b-5p suppress migration and invasion of bladder cancer cells through targetting ZEB2

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Suogang Wang ◽  
Geng Zhang ◽  
Wanxiang Zheng ◽  
Qin Xue ◽  
Di Wei ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Migration And Invasion ◽  
Pcr Analysis ◽  
Inhibitory Effects ◽  
Mesenchymal Transition ◽  
Expression Levels ◽  
Invasion And Migration ◽  
And Migration

Bladder cancer (BCa) threatens human health due to the high occurrence and mortality. Nowadays, more and more researchers focussed on the molecular mechanisms and biological functions of miRNAs in human cancers. The present study aims to study the biological role of miR-454-3p and miR-374b-5p in BCa. The expression levels of miR-454-3p and miR-374b-5p were detected in BCa tissues and cell lines by qRT-PCR analysis. Kaplan–Meier analysis revealed that the expression levels of miR-454-3p and miR-374b-5p were positively correlated with the overall survival (OS) rate of BCa patients. Gain-of-function assays were conducted to demonstrate the inhibitory effects of miR-454-3p and miR-374b-5p on the invasion, migration, and epithelial–mesenchymal transition (EMT) of BCa cells. Mechanically, ZEB2 was found to be a target of both miR-454-3p and miR-374b-5p. Rescue assays revealed that ZEB2 reversed the inhibitory effects of miR-454-3p and miR-374b-5p on the invasion and migration of BCa cell lines. In summary, miR-454-3p and miR-374b-5p negatively regulated invasion and migration of BCa cell lines via targetting ZEB2.

scholarly journals circVAPA promotes the proliferation, migration and invasion of oral cancer cells through the miR-132/HOXA7 axis

2021 ◽  
Vol 49 (6) ◽  
pp. 030006052110132
Author(s):  
Hao Chen ◽  
Ye Zhang ◽  
Kankui Wu ◽  
Xiaoyong Qiu
Keyword(s):  
Oral Cancer ◽  
Cancer Cells ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Invasion And Migration ◽  
Oral Cancer Cells ◽  
And Migration

Objective To study the relationship between the circular RNA vesicle-associated membrane protein-associated protein A (circVAPA) and the pathogenesis of oral squamous cell carcinoma. Methods The expression of circVAPA was detected by RT-qPCR. In vitro loss-of-function experiments were performed in Cal-27 cells. The malignant phenotype of cells was evaluated by cell counting kit-8, clone formation and transwell assays. Luciferase reporter assays were used to assess the circVAPA/miR-132/homeobox A (HOXA) regulatory axis. Results circVAPA expression was significantly increased in oral cancer tissues and cells. The overall survival and progression-free survival of patients with oral cancer who exhibited high circVAPA expression were significantly shorter compared with those with low expression. circVAPA expression was closely related to tumor size, TNM stage and distant metastasis. circVAPA knockdown reduced the proliferation, invasion and migration of Cal-27 cells. MiR-132 was identified as a target of circVAPA in Cal-27 cells. Cotransfection with si-circVAPA and miR-132 inhibitor reversed the inhibitory effect of circVAPA knockdown on cell malignant phenotypes. HOXA7 was further identified as a downstream target of miR-132. Conclusion circVAPA is highly expressed in oral cancer, and its abnormal expression might affect the proliferation, invasion and migration of oral cancer cells by modulating the miR-132/HOXA7 signaling axis.

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