scholarly journals A negative feedback loop between long noncoding RNA NBAT1 and Sox9 inhibits the malignant progression of gastric cancer cells

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Jijun Yan ◽  
Wenwei Huang ◽  
Xiufang Huang ◽  
Wencai Xiang ◽  
Chao Ye ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Negative Feedback ◽  
Noncoding Rna ◽  
Feedback Loop ◽  
Capillary Tube ◽  
Umbilical Vein ◽  
Tumor Stage ◽  
Migration And Invasion ◽  
Negative Feedback Loop ◽  
Gastric Cancer Cells

Long noncoding RNAs (lncRNAs) play critical roles in carcinogenesis and progression, and act as important gene expression modulators. Recent evidence indicates that lncRNA neuroblastoma associated transcript 1 (NBAT1) functions as a tumor suppressor in some types of human cancers. However, its functional role in the development of gastric cancer (GC) remains unknown. The aim of this research was to investigate the clinical significance and biological functions of NBAT1 in GC. NBAT1 was found to be significantly down-regulated in GC tissue. Decreased NBAT1 expression was correlated with poor differentiation, higher tumor stage and lymph node metastasis, and poor prognosis. Functional assays showed that NBAT1 inhibited GC proliferation, migration, and invasion. NBAT1 also suppressed proliferation, migration, and capillary tube formation of human umbilical vein endothelial cells (HUVECs). Mechanistically, NBAT1 interacted with Sox9, and reduced its protein stability by promoting it from polyubiquitination and proteasome-dependent degradation. Moreover, we revealed that Sox9 could occupy the NBAT1 promoter to inactivate its transcription. The negative feedback loop of NBAT1 and Sox9 continuously enhanced the suppressive effects. In conclusion, these findings suggest that feedback regulation of NBAT1 and Sox9 served as a critical effector in GC progression.

scholarly journals Epigenetically deregulated miR-200c is involved in a negative feedback loop with DNMT3a in gastric cancer cells

2016 ◽  
Vol 36 (4) ◽  
pp. 2108-2116 ◽  
Author(s):  
Yingfei Li ◽  
Yuqiang Nie ◽  
Sanfang Tu ◽  
Hong Wang ◽  
Yongjian Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Negative Feedback Loop ◽  
Gastric Cancer Cells

scholarly journals Identification of a novel YAP-14-3-3ζ negative feedback loop in gastric cancer

Oncotarget ◽  
2017 ◽  
Vol 8 (42) ◽  
pp. 71894-71910 ◽  
Author(s):  
Bin Zhang ◽  
Aihua Gong ◽  
Hui Shi ◽  
Qingli Bie ◽  
Zhaofeng Liang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Negative Feedback Loop

scholarly journals MiR-29a Inhibits Glioma Tumorigenesis through a Negative Feedback Loop of TRAF4/Akt Signaling

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Yongjie Liu ◽  
Naiquan Duan ◽  
Shibo Duan
Keyword(s):  
Cell Proliferation ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Akt Signaling ◽  
Luciferase Reporter ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Negative Feedback Loop ◽  
Expression Correlation ◽  
Qrt Pcr

Background. MiR-29a is known as a repressor of human cancer. However, its relevance in glioma proliferation and invasion remains largely unknown. In this study, we aimed to investigate the function and mechanism of miR-29a in glioma tumorigenesis.Methods. The expression of miR-29a was determined by using qRT-PCR. CCK-8, wound healing, and transwell invasion assays were carried out to analyze the effects of miR-29a in glioblastoma cells. qRT-PCR, luciferase reporter, and western blot experiments were done to validate the targeting of TRAF4/Akt pathway by miR-29a. The expression correlation between levels of TRAF4 and miR-29a was analyzed. Regulation of miR-29a expression by enhanced/reduced TRAF4/Akt expression was finally confirmed by qRT-PCR.Results. MiR-29a was decreased in the glioma tissues, especially in those at higher grades. Following its mimic transfection, we validated that miR-29a inhibited cell proliferation, migration, and invasion. Consistently, miR-29a inhibition induced the opposite effects on cell proliferation, migration, and invasion. We confirmed TRAF4 as a direct target of miR-29a, which might mediate the Akt pathway activation. We showed a significantly negative expression correlation between TRAF4 and miR-29a in normal and glioma tissues. Finally we observed an upregulation of miR-29a in TRAF4/Akt activated cells.Conclusion. MiR-29a is critical tumor suppressor for glioma tumorigenesis by forming a negative feedback loop of TRAF4/Akt signaling and represents a potent therapeutic candidate for treating gliomas.

scholarly journals LncRNA DANCR promotes migration and invasion through suppression of lncRNA-LET in gastric cancer cells

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Zhengqiang Mao ◽  
Hang Li ◽  
Botao Du ◽  
Kai Cui ◽  
Yuguang Xing ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Clinical Stage ◽  
Epigenetic Mechanism ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Gastrointestinal Malignancies ◽  
Cell Migration And Invasion

Gastric cancer (GC) is one of the most prevalent gastrointestinal malignancies. Long noncoding RNA (lncRNA) DANCR is a newly identified oncogenic lncRNA. However, the functional role and underlying molecular mechanisms of DANCR involved in GC progress remain unclear. In the present study, we investigated the biological function and underlying mechanisms of DANCR in GC cell migration and invasion. The results showed that knockdown of DANCR inhibited migration and invasion of GC cells, whereas overexpression of DANCR showed the opposite effect. Further investigation demonstrated that lncRNA-LET was a bona fide target gene of DANCR. In addition, high DANCR and low lncRNA-LET were significantly correlated with lymph node metastasis and late clinical stage. DANCR associated with EZH2 and HDAC3 to epigenetically silence lncRNA-LET and then regulated GC migration and invasion. Taken together, these findings indicate an important role for DANCR–lncRNA-LET axis in GC cell migration and invasion, and reveal a novel epigenetic mechanism for lncRNA-LET silencing.

scholarly journals A Direct Negative Feedback Loop of miR-4721/FOXA1/Nanog Promotes Nasopharyngeal Cell Stem Cell Enrichment and Metastasis 

2021 ◽  
Author(s):  
Mengyang Zhao ◽  
Zibo Tang ◽  
Yijun Wang ◽  
Jiaojiao Ding ◽  
Ying Guo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Side Population ◽  
Nasopharyngeal Cancer ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Negative Feedback Loop ◽  
Linkage Mechanism

Abstract Objective: The recurrence and metastasis of nasopharyngeal cancer (NPC) may be mainly attributed to the persistence of cancer stem cells (CSCs); however, the linkage mechanism has yet to be fully elucidated. Methods: The levels of miR-4721, FOXA1, and Nanog expression in NPC were detected by in situ hybridization and immunohistochemistry. In vivo and in vitro metastasis assays confirmed miR-4721 promotes cell migration and invasion. Tumor spheroid formation assay, side population (SP) assay, and ALDEFLUOR assay verified miR-4721 regulates cancer stem cell-like properties. Luciferase reporter assay showed that miR-4721 directly regulates FOXA1 and FOXA1 effects the promoter activity of miR-4721 and Nanog. Chromatin immunoprecipitation (ChIP) analysis and electrophoresis mobility shift assay (EMSA) revealed that FOXA1 combined the promoter region of human miR-4721 and Nanog and the possible mechanism was also analyzed.Results: In this study, a new mechanism of NPC tumorigenesis related to miR-4721 was verified. We found that miR-4721, FOXA1 and Nanog control their expressions through a negative feedback loop and then activate the downstream regulator of stem cell signaling to promote the enrichment and metastasis of NPC stem cells. Conclusion: These findings elucidate that the feedback loop of miR-4721/FOXA1/Nanog can regulate stemness and metastasis in NPC and may provide an experimental theoretical basis for metastasis and treatment resistance in NPC.

scholarly journals A direct negative feedback loop of miR-4721/FOXA1/Nanog promotes nasopharyngeal cell stem cell enrichment and metastasis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Mengyang Zhao ◽  
Zibo Tang ◽  
Yijun Wang ◽  
Jiaojiao Ding ◽  
Ying Guo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Side Population ◽  
Nasopharyngeal Cancer ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Negative Feedback Loop ◽  
Linkage Mechanism

Abstract Objective The recurrence and metastasis of nasopharyngeal cancer (NPC) may be mainly attributed to the persistence of cancer stem cells (CSCs); however, the linkage mechanism has yet to be fully elucidated. Methods The levels of miR-4721, FOXA1, and Nanog expression in NPC were detected by in situ hybridization and immunohistochemistry. In vivo and in vitro metastasis assays confirmed miR-4721 promotes cell migration and invasion. Tumor spheroid formation assay, side population (SP) assay, and ALDEFLUOR assay verified miR-4721 regulates cancer stem cell-like properties. Luciferase reporter assay showed that miR-4721 directly regulates FOXA1 and FOXA1 effects the promoter activity of miR-4721 and Nanog. Chromatin immunoprecipitation (ChIP) analysis and electrophoresis mobility shift assay (EMSA) revealed that FOXA1 combined the promoter region of human miR-4721 and Nanog and the possible mechanism was also analyzed. Results In this study, a new mechanism of NPC tumorigenesis related to miR-4721 was verified. We found that miR-4721, FOXA1 and Nanog control their expressions through a negative feedback loop and then activate the downstream regulator of stem cell signaling to promote the enrichment and metastasis of NPC stem cells. Conclusion These findings elucidate that the feedback loop of miR-4721/FOXA1/Nanog can regulate stemness and metastasis in NPC and may provide an experimental theoretical basis for metastasis and treatment resistance in NPC.

scholarly journals Long noncoding RNA LINC00518 induces radioresistance by regulating glycolysis through an miR-33a-3p/HIF-1α negative feedback loop in melanoma

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Yan Liu ◽  
Dong He ◽  
Mengqing Xiao ◽  
Yuxing Zhu ◽  
Jianda Zhou ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Cancer Progression ◽  
Negative Feedback ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Feedback Loop ◽  
Negative Feedback Loop ◽  
Histone Deacetylase 2

AbstractThe long noncoding RNA, LINC00518, is highly expressed in various types of cancers and is involved in cancer progression. Although LINC00518 promotes the metastasis of cutaneous malignant melanoma (CMM), the mechanism underlaying its effects on CMM radiosensitivity remains unclear. In this study, LINC00518 expression was significantly upregulated in CMM samples, and LINC00518 levels were associated with poor prognosis of patients with CMM. Knockdown of LINC00518 in CMM cells significantly inhibited cell invasion, migration, proliferation, and clonogenicity. LINC00518-mediated invasion, migration, proliferation, and clonogenicity were negatively regulated by the microRNA, miR-33a-3p, in vitro, which increased sensitivity to radiotherapy via inhibition of the hypoxia-inducible factor 1α (HIF-1α)/lactate dehydrogenase A glycolysis axis. Additionally, HIF-1α recognized the miR-33a-3p promoter region and recruited histone deacetylase 2, which decreased the expression of miR-33a-3p and formed an LINC00518/miR-33a-3p/HIF-1α negative feedback loop. Furthermore, signaling with initially activated glycolysis and radioresistance in CMM cells was impaired by Santacruzamate A, a histone deacetylase inhibitor, and 2-deoxy-D-glucose, a glycolytic inhibitor. Lastly, knockdown of LINC00518 expression sensitized CMM cancer cells to radiotherapy in an in vivo subcutaneously implanted tumor model. In conclusion, LINC00518 was confirmed to be an oncogene in CMM, which induces radioresistance by regulating glycolysis through an miR-33a-3p/HIF-1α negative feedback loop. Our study, may provide a potential strategy to improve the treatment outcome of radiotherapy in CMM.

scholarly journals MicroRNA-22 suppresses the growth, migration and invasion of colorectal cancer cells through a Sp1 negative feedback loop

Oncotarget ◽  
2017 ◽  
Vol 8 (22) ◽  
pp. 36266-36278 ◽  
Author(s):  
Shu-Sen Xia ◽  
Guang-Jun Zhang ◽  
Zuo-Liang Liu ◽  
Hong-Peng Tian ◽  
Yi He ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Negative Feedback ◽  
Feedback Loop ◽  
Migration And Invasion ◽  
Negative Feedback Loop ◽  
Colorectal Cancer Cells
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