scholarly journals Low Expression of miR-491 Promotes Esophageal Cancer Cell Invasion by Targeting TPX2

2015 ◽  
Vol 36 (6) ◽  
pp. 2263-2273 ◽  
Author(s):  
Hongyan Niu ◽  
Li Gong ◽  
Xiaofeng Tian ◽  
Liangwei Fang ◽  
Chengxiang Wang ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Clinical Samples ◽  
Regulation Mechanism ◽  
Aberrant Expression ◽  
Tumor Tissues ◽  
Esophageal Cancer Cell ◽  
Emt Markers

Background/Aims: MicroRNAs (miRNAs) have a key role in carcinogenesis and cancer development, but the role of miRNAs in the progression of esophageal cancer (EC) remains unclear. Methods: The TE-1 and Eca-109 EC cell lines were used. The expression of miR-491 and candidate gene TPX2 in EC samples (n=99) were detected by RT-PCR. The cells invasive ability was determined by transwell assay. The luciferase reporter assay was used to confirm the regulation mechanism. Results: A decreased expression of miR-491 was detected in the EC clinical samples compared with the corresponding adjacent tumor tissues. Aberrant expression of miR-491 regulated cells invasion and EMT markers. Furthermore, we verified that TPX2 was a target gene of miR-491. Conclusions: miR-491 may play a critical role in EC.

scholarly journals LncRNA MAGI2-AS3 Overexpression Sensitizes Esophageal Cancer Cells to Irradiation Through Down-Regulation of HOXB7 via EZH2

2020 ◽  
Vol 8 ◽  
Author(s):  
Wenfang Cheng ◽  
Xiuling Shi ◽  
Mingqiang Lin ◽  
Qiwei Yao ◽  
Jiayu Ma ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Cells ◽  
Potential Role ◽  
Luciferase Reporter ◽  
Cancer Resistance ◽  
Down Regulation ◽  
Aberrant Expression ◽  
Gene Assay ◽  
Esophageal Cancer Cells

BackgroundAccumulating evidence has suggested that aberrant expression of long non-coding RNAs (lncRNAs) may contribute to cancer progression in association with radioresistance. The current study aimed to identify the potential role of lncRNA MAGI2-AS3 and the underlying mechanism in its regulation of the radio-sensitivity of esophageal cancer cells.Methods and ResultsInitially, we detected high expression of HOXB7 from microarray-based gene expression profiling of esophageal cancer. Then, we identified the interactions among MAGI2-AS3, HOXB7, and EZH2 by dual-luciferase reporter gene assay, RNA pull-down assay, RIP assay and ChIP assay. HOXB7 was highly-expressed, while MAGI2-AS3 was poorly-expressed in esophageal cancer tissues and cells. The effect of MAGI2-AS3 and HOXB7 on esophageal cancer cell proliferation and apoptosis as well as tumorigenicity of radioresistant cells was examined by gain- and loss-of-function experiments. Interestingly, MAGI2-AS3 down-regulated HOXB7 through interaction with EZH2, which promoted cell apoptosis and inhibited proliferation and radio-resistance. Besides, down-regulation of MAGI2-AS3 exerted a promoting effect on these malignant phenotypes.ConclusionTaken together, our results reveal the potential role of MAGI2-AS3 over-expression in controlling esophageal cancer resistance to radiotherapy by down-regulating HOXB7, this providing a candidate biomarker for resistance to radiotherapy.

Exosomal miR-214-5p Released from Glioblastoma Cells Modulates Inflammatory Response of Microglia after Lipopolysaccharide Stimulation through Targeting CXCR5

2019 ◽  
Vol 18 (1) ◽  
pp. 78-87 ◽  
Author(s):  
Jian-kai Yang ◽  
Hong-jiang Liu ◽  
Yuanyu Wang ◽  
Chen Li ◽  
Ji-peng Yang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Clinical Prognosis ◽  
Direct Target ◽  
And Migration ◽  
High Level ◽  
Cxcr5 Expression ◽  
Proliferation And Migration

Background and Objective: Exosomes communicate inter-cellularly and miRNAs play critical roles in this scenario. MiR-214-5p was implicated in multiple tumors with diverse functions uncovered. However, whether miR-214-5p is mechanistically involved in glioblastoma, especially via exosomal pathway, is still elusive. Here we sought to comprehensively address the critical role of exosomal miR-214-5p in glioblastoma (GBM) microenvironment.Methods:The relative expression of miR-214-5p was determined by real-time PCR. Cell viability and migration were measured by MTT and transwell chamber assays, respectively. The secretory cytokines were measured with ELISA kits. The regulatory effect of miR-214-5p on CXCR5 expression was interrogated by luciferase reporter assay. Protein level was analyzed by Western blot.Results:We demonstrated that miR-214-5p was aberrantly overexpressed in GBM and associated with poorer clinical prognosis. High level of miR-214-5p significantly contributed to cell proliferation and migration. GBM-derived exosomal miR-214-5p promoted inflammatory response in primary microglia upon lipopolysaccharide challenge. We further identified CXCR5 as the direct target of miR-214- 5p in this setting.Conclusion:Overexpression of miR-214-5p in GBM modulated the inflammatory response in microglia via exosomal transfer.

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

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

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

scholarly journals miR-205 in Breast Cancer: State of the Art

2020 ◽  
Vol 22 (1) ◽  
pp. 27
Author(s):  
Ilaria Plantamura ◽  
Alessandra Cataldo ◽  
Giulia Cosentino ◽  
Marilena V. Iorio
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Normal Breast ◽  
Response To Therapy ◽  
Aberrant Expression ◽  
Open Questions ◽  
Tumor Tissues ◽  
Breast Physiology ◽  
Cancer Types

Despite its controversial roles in different cancer types, miR-205 has been mainly described as an oncosuppressive microRNA (miRNA), with some contrasting results, in breast cancer. The role of miR-205 in the occurrence or progression of breast cancer has been extensively studied since the first evidence of its aberrant expression in tumor tissues versus normal counterparts. To date, it is known that the expression of miR-205 in the different subtypes of breast cancer is decreasing from the less aggressive subtype, estrogen receptor/progesterone receptor positive breast cancer, to the more aggressive, triple negative breast cancer, influencing metastasis capability, response to therapy and patient survival. In this review, we summarize the most important discoveries that have highlighted the functional role of this miRNA in breast cancer initiation and progression, in stemness maintenance, in the tumor microenvironment, its potential role as a biomarker and its relevance in normal breast physiology—the still open questions. Finally, emerging evidence reveals the role of some lncRNAs in breast cancer progression as sponges of miR-205. Here, we also reviewed the studies in this field.

scholarly journals MiR-125b regulates inflammation in bovine mammary epithelial cells by targeting the NKIRAS2 gene

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Zhuo-Ma Luoreng ◽  
Da-Wei Wei ◽  
Xing-Ping Wang
Keyword(s):  
T Cells ◽  
Epithelial Cells ◽  
Dairy Cows ◽  
Mammary Epithelial Cells ◽  
Mammary Epithelial ◽  
Luciferase Reporter ◽  
Regulation Mechanism ◽  
Bovine Mammary Epithelial Cells ◽  
Tnf Α

AbstractMastitis is a complex inflammatory disease caused by pathogenic infection of mammary tissue in dairy cows. The molecular mechanism behind its occurrence, development, and regulation consists of a multi-gene network including microRNA (miRNA). Until now, there is no report on the role of miR-125b in regulating mastitis in dairy cows. This study found that miR-125b expression is significantly decreased in lipopolysaccharide (LPS)-induced MAC-T bovine mammary epithelial cells. Also, its expression is negatively correlated with the expression of NF-κB inhibitor interacting Ras-like 2 (NKIRAS2) gene. MiR-125b target genes were identified using a double luciferase reporter gene assay, which showed that miR-125b can bind to the 3′ untranslated region (3′ UTR) of the NKIRAS2, but not the 3′UTR of the TNF-α induced protein 3 (TNFAIP3). In addition, miR-125b overexpression and silencing were used to investigate the role of miR-125b on inflammation in LPS-induced MAC-T. The results demonstrate that a reduction in miR-125b expression in LPS-induced MAC-T cells increases NKIRAS2 expression, which then reduces NF-κB activity, leading to low expression of the inflammatory factors IL-6 and TNF-α. Ultimately, this reduces the inflammatory response in MAC-T cells. These results indicate that miR-125b is a pro-inflammatory regulator and that its silencing can alleviate bovine mastitis. These findings lay a foundation for elucidating the molecular regulation mechanism of cow mastitis.

scholarly journals Polo-Like Kinase 4’s Critical Role in Cancer Development and Strategies for Plk4-Targeted Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaoyang Zhang ◽  
Cheng Wei ◽  
Hao Liang ◽  
Lei Han
Keyword(s):  
Cell Cycle ◽  
Cancer Diagnosis ◽  
Molecular Level ◽  
Critical Role ◽  
Cancer Development ◽  
Tumor Biomarker ◽  
Hallmarks Of Cancer ◽  
Aberrant Expression ◽  
Cancer Diagnosis And Therapy

Polo-like kinases (Plks) are critical regulatory molecules during the cell cycle process. This family has five members: Plk1, 2, 3, 4, and 5. Plk4 has been identified as a master regulator of centriole replication, and its aberrant expression is closely associated with cancer development. In this review, we depict the DNA, mRNA, and protein structure of Plk4, and the regulation of Plk4 at a molecular level. Then we list the downstream targets of Plk4 and the hallmarks of cancer associated with these targets. The role of Plk4 in different cancers is also summarized. Finally, we review the inhibitors that target Plk4 in the hope of discovering effective anticancer drugs. From authors’ perspective, Plk4 might represent a valuable tumor biomarker and critical target for cancer diagnosis and therapy.

scholarly journals Identification of a Modified HOXB9 mRNA in Breast Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ayako Nakashoji ◽  
Tetsu Hayashida ◽  
Yuko Kawai ◽  
Masayuki Kikuchi ◽  
Rurina Watanuki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Cancer Cell Line ◽  
Clinical Samples ◽  
The Novel ◽  
Rna Seq ◽  
Human Breast ◽  
Aberrant Expression ◽  
Novel Variant

First identified as a developmental gene, HOXB9 is also known to be involved in tumor biological processes, and its aberrant expression correlates with poor prognosis of various cancers. In this study, we isolated a homeodomain-less, novel HOXB9 variant (HOXB9v) from human breast cancer cell line-derived mRNA. We confirmed that the novel variant was produced from variationless HOXB9 genomic DNA. RT-PCR of mRNA isolated from clinical samples and reanalysis of publicly available RNA-seq data proved that the new transcript is frequently expressed in human breast cancer. Exogenous HOXB9v expression significantly enhanced the proliferation of breast cancer cells, and gene ontology analysis indicated that apoptotic signaling was suppressed in these cells. Considering that HOXB9v lacks key domains of homeobox proteins, its behavior could be completely different from that of the previously described variationless HOXB9. Because none of the previous studies on HOXB9 have considered the presence of HOXB9v, further research analyzing the two transcripts individually is warranted to re-evaluate the true role of HOXB9 in cancer.

scholarly journals LncRNA LUADT1 sponges miR-195 to prevent cardiac endothelial cell apoptosis in sepsis

2020 ◽  
Vol 26 (1) ◽  
Author(s):  
Zhimin Zhang ◽  
Mingzhu Lv ◽  
Xiang Wang ◽  
Zheng Zhao ◽  
Daolong Jiang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Critical Role ◽  
Potential Interaction ◽  
Luciferase Reporter ◽  
Endothelial Cell Apoptosis ◽  
Luciferase Activity Assay ◽  
Apoptosis Related Protein

Abstract Background The oncogenic role of the newly identified lncRNA LUADT1 has been revealed in lung adenocarcinoma. It was reported that LUADT1 plays a critical role in multiple human diseases. This study was carried out to investigate the role of LUADT1 in sepsis. Methods Sixty patients with sepsis and sixty healthy volunteers were recruited for this study. Plasma samples were collected from all participants. Human primary coronary artery endothelial cells were also used in this study. The expression of Pim-1, miR-195 and LUADT1 were detected by RT-qPCR. The interaction between miR-195 and LUADT1 was determined by overexpression experiments and luciferase activity assay. Cell apoptosis was detected by flow cytometry. The expression of apoptosis-related protein was detected by Western blotting. Results Bioinformatics analysis revealed the potential interaction between LUADT1 and miR-195, which was confirmed by dual luciferase reporter assay. LUADT1 was downregulated in patients with sepsis. Moreover, LPS treatment downregulated the expression of LUADT1 in primary cardiac endothelial cells. Overexpression of LUADT1 and miR-195 did not affect the expression of each other in primary cardiac endothelial cells. Interestingly, overexpression of LUADT1 was found to upregulate the expression of Pim-1, a target of miR-195. In addition, it was found that overexpression of LUADT1 and Pim-1 reduced the enhancement effects of miR-195 on LPS-induced cardiac endothelial cell apoptosis. Conclusion In summary, LUADT1 may protect cardiac endothelial cells against apoptosis in sepsis by regulating the miR-195/Pim-1 axis.

scholarly journals Circular RNA hsa_circ_0007142 Is Upregulated and Targets miR-103a-2-5p in Colorectal Cancer

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Chang-li Zhu ◽  
Xiaofeng Sha ◽  
Yuan Wang ◽  
Jin Li ◽  
Men-yan Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Bioinformatic Analysis ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Circular Rnas ◽  
Aberrant Expression ◽  
Poor Differentiation ◽  
Hct 116 Cells

Circular RNAs (circRNAs) are a large class of endogenous noncoding RNAs that regulate gene expression and mainly function as microRNA sponges. This study aimed to explore the aberrant expression of circRNAs in colorectal cancer (CRC). Using a circRNA microarray, we identified 892 differentially expressed circRNAs between six pairs of CRC and adjacent paracancerous tissues. Among them, hsa_circ_0007142 was significantly upregulated. Further analysis in 50 CRC clinical samples revealed that hsa_circ_0007142 upregulation was associated with poor differentiation and lymphatic metastasis of CRC. Bioinformatic analysis and luciferase reporter assay showed that hsa_circ_0007142 targeted miR-103a-2-5p in CRC cells. Moreover, the silencing of hsa_circ_0007142 by siRNAs decreased the proliferation, migration, and invasion of HT-29 and HCT-116 cells. Taken together, these findings suggest that hsa_circ_0007142 is upregulated in CRC and targets miR-103a-2-5p to promote CRC.

scholarly journals PBX2-Mediated circTLK1 Activates JAK/STAT Signaling to Promote Gliomagenesis via miR-452-5p/SSR1 Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Li ◽  
Zongren Zhao ◽  
Xiang Wang ◽  
Qiong Ma ◽  
Huanhuan Ji ◽  
...  
Keyword(s):  
Glioma Cells ◽  
Luciferase Reporter ◽  
High Morbidity ◽  
The Novel ◽  
Luciferase Reporter Gene ◽  
Upstream Regulator ◽  
Tumor Tissues ◽  
Stat Signaling ◽  
Series Of Experiments

Glioma is considered one of the most lethal brain tumors, as the aggressive blood vessel formation leads to high morbidity and mortality rates. However, the mechanisms underlying the initiation and progression of glioma remain unclear. Here, we aimed to reveal the role of circTLK1 in glioma development. Our results revealed that circTLK1 is highly expressed in glioma tumor tissues and glioma cell lines. We then conducted a series of experiments that showed that circTLK1 was involved in the progression of gliomas. Mechanistically, investigation of the factors downstream of circTLK1 revealed that circTLK1 activated JAK/STAT signaling in glioma cells. Furthermore, AGO2-RIP, RNA-pull down, and luciferase reporter gene assays led to the identification of the novel circTLK1/miR-452-5p/SSR1 axis. Moreover, we investigated the upstream regulator of circTLK1 and found that circTLK1 expression in glioma cells could be regulated by the transcriptional factor PBX2. Taken together, our findings show that circTLK1 mediated by PBX2 activates JAK/STAT signaling to promote glioma progression through the miR-452-5p/SSR1 pathway. These results provide new insights into glioma diagnosis and therapy.

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