The long non-coding RNA FOXD2-AS1 promotes bladder cancer progression and recurrence through a positive feedback loop with Akt and E2F1

Abstract Acute myeloid leukaemia (AML) is a frequently diagnosed malignancy in adults. Long non-coding RNA (lncRNA) colon cancer-associated transcript 1 (CCAT1) has been well known to play vital roles in multiple malignancies including AML. Unfortunately, the detailed mechanism of CCAT1 in AML progression remains obscure. In this study, we demonstrated that CCAT1 was up-regulated in AML samples while its target, miR-490-3p, was relatively down-regulated. CCAT1 markedly increased viability and metastasis of AML cells, while miR-490-3p had opposite effects. CCAT1 could specifically bind to miR-490-3p and reduce its expression and activity, and MAPK1 was a target gene of miR-490-3p. Overexpressed CCAT1 could induce MAPK1 expression and c-Myc reciprocally increased CCAT1 expression. Our data implied that miR-490-3p could be a novel therapeutic target for AML, and highlights the crucial role of CCAT1/miR-490-3p/MAPK1/c-Myc positive feedback loop in AML progression.

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Long Non-Coding RNA CASC9 And HIF-1α Form A Positive Feedback Loop To Facilitate Cell Proliferation And Metastasis In Lung Cancer

OncoTargets and Therapy ◽

10.2147/ott.s226078 ◽

2019 ◽

Vol Volume 12 ◽

pp. 9017-9027 ◽

Cited By ~ 3

Author(s):

Yuxing Jin ◽

Huikang Xie ◽

Liang Duan ◽

Deping Zhao ◽

Jiaan Ding ◽

...

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

Positive Feedback ◽

Feedback Loop ◽

Positive Feedback Loop ◽

Non Coding Rna ◽

Proliferation And Metastasis ◽

Long Non Coding Rna ◽

Cell Proliferation And Metastasis

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LncRNA PVT1 Promotes Bladder Cancer Progression by Forming a Positive Feedback Loop With STAT5B

10.21203/rs.3.rs-883550/v1 ◽

2021 ◽

Author(s):

Zhuo Li ◽

Jian Liu ◽

Huifeng Fu ◽

Yuanwei Li ◽

Qaing Lu ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Progression ◽

Positive Feedback ◽

Feedback Loop ◽

Bioinformatic Analysis ◽

Luciferase Reporter ◽

Positive Feedback Loop ◽

Rna Immunoprecipitation ◽

Transcriptional Effect

Abstract Background: Plasmacytoma Variant Translocation 1 (LncRNA PVT1) and signal transducer and activator of transcription 5B (STAT5B) have been reported to play important roles in various cancers, but their interaction in bladder cancer (BC) remains unclear. Purpose: In this study, we aimed to explore the interaction between lncRNA PVT1 and STAT5B in BC tumorigenesis. Methods: The association of the expression of the lncRNA PVT1 and STAT5B to the prognosis of patient with BC was evaluated via bioinformatic analysis. Loss- and gain-of-function assays were performed to determine the biological functions of lncRNA PVT1 and STAT5B in BC cells. Quantitative real time polymerase chain reaction, Western blot, immunohistochemistry, and immunofluorescence were used to detect lncRNA PVT1 and STAT5B expression. Fluorescence in situ hybridization, RNA pull-down and RNA immunoprecipitation assays were conducted to determine the regulatory effect of lncRNA PVT1 on STAT5B. The transcriptional effect of STAT5B on lncRNA PVT1 gene was determined using luciferase reporter assay, chromatin immunoprecipitation and DNA-affinity precipitation assays.Results: We found that lncRNA PVT1 and STAT5B enhance the expression of each other and promote the malignant phenotypes in BC, including cell viability and invasion. lncRNA PVT1 stabilizes STAT5B by decreasing ubiquitination, enhances STAT5B phosphorylation, and promotes the translocation to the nucleus of STAT5B to trigger further carcinogenesis activities. In the nucleus, STAT5B activates the transcription of lncRNA PVT1 by binding directly to its promoter region, leading to a positive feedback.Conclusions: We first identified the lncRNA PVT1/STAT5B positive feedback loop for bladder carcinogenesis, which may provide new molecular targets for interventions of BC.

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DEAD-box protein p68 is regulated by β-catenin/transcription factor 4 to maintain a positive feedback loop in control of breast cancer progression

Breast Cancer Research ◽

10.1186/s13058-014-0496-5 ◽

2014 ◽

Vol 16 (6) ◽

Cited By ~ 21

Author(s):

Kiran Kumar Naidu Guturi ◽

Moumita Sarkar ◽

Arijit Bhowmik ◽

Nilanjana Das ◽

Mrinal Kanti Ghosh

Keyword(s):

Breast Cancer ◽

Transcription Factor ◽

Cancer Progression ◽

Positive Feedback ◽

Feedback Loop ◽

Breast Cancer Progression ◽

Positive Feedback Loop ◽

Dead Box ◽

Transcription Factor 4

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ETS Transcription Factor ESE1/ELF3 Orchestrates a Positive Feedback Loop That Constitutively Activates NF-κB and Drives Prostate Cancer Progression

Cancer Research ◽

10.1158/0008-5472.can-12-4537 ◽

2013 ◽

Vol 73 (14) ◽

pp. 4533-4547 ◽

Cited By ~ 42

Author(s):

Nicole Longoni ◽

Manuela Sarti ◽

Domenico Albino ◽

Gianluca Civenni ◽

Anastasia Malek ◽

...

Keyword(s):

Prostate Cancer ◽

Transcription Factor ◽

Cancer Progression ◽

Positive Feedback ◽

Feedback Loop ◽

Prostate Cancer Progression ◽

Positive Feedback Loop ◽

Ets Transcription Factor

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A Positive Feedback Loop of lncRNA MIR31HG-miR-361-3p -YY1 Accelerates Colorectal Cancer Progression Through Modulating Proliferation, Angiogenesis, and Glycolysis

Frontiers in Oncology ◽

10.3389/fonc.2021.684984 ◽

2021 ◽

Vol 11 ◽

Author(s):

Tao Guo ◽

Defeng Liu ◽

Shihao Peng ◽

Meng Wang ◽

Yangyang Li

Keyword(s):

Colorectal Cancer ◽

Cancer Progression ◽

Positive Feedback ◽

Feedback Loop ◽

Luciferase Reporter ◽

Loss Of Function ◽

Positive Feedback Loop ◽

Related Proteins

BackgroundColorectal cancer (CRC) is a common malignant tumor with high metastatic and recurrent rates. This study probes the effect and mechanism of long non-coding RNA MIR31HG on the progression of CRC cells.Materials and MethodsQuantitative real-time PCR (qRT-PCR) was used to analyze the expression of MIR31HG and miR-361-3p in CRC tissues and normal tissues. Gain- or loss-of-function assays were conducted to examine the roles of MIR31HG, miR-361-3p and YY1 transcription factor (YY1) in the CRC progression. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and colony formation experiment were conducted to test CRC cell proliferation. CRC cell invasion was determined by Transwell assay. The glucose detection kit and lactic acid detection kit were utilized to monitor the levels of glucose and lactate in CRC cells. The glycolysis level in CRC cells was examined by the glycolytic stress experiment. Western blot was performed to compare the expression of glycolysis-related proteins (PKM2, GLUT1 and HK2) and angiogenesis-related proteins (including VEGFA, ANGPT1, HIF1A and TIMP1) in HUVECs. The binding relationships between MIR31HG and miR-361-3p, miR-361-3p and YY1 were evaluated by the dual-luciferase reporter assay and RNA immunoprecipitation (RIP).ResultsMIR31HG was up-regulated in CRC tissues and was associated with poorer prognosis of CRC patients. The in-vitro and in-vivo experiments confirmed that overexpressing MIR31HG heightened the proliferation, growth, invasion, glycolysis and lung metastasis of CRC cells as well as the angiogenesis of HUVECs. In addition, MIR3HG overexpression promoted YY1 mRNA and protein level, and forced overexpression of YY1 enhanced MIR31HG level. Overexpressing YY1 reversed the tumor-suppressive effect mediated by MIR31HG knockdown. miR-361-3p, which was inhibited by MIR31HG overexpression, repressed the malignant behaviors of CRC cells. miR-361-3p-mediated anti-tumor effects were mostly reversed by upregulating MIR31HG. Further mechanism studies illustrated that miR-361-3p targeted and negatively regulated the expression of YY1.ConclusionThis study reveals that MIR31HG functions as an oncogenic gene in CRC via forming a positive feedback loop of MIR31HG-miR-361-3p-YY1.

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The Establishment of CDK9/ RNA PolII/H3K4me3/DNA Methylation Feedback Promotes HOTAIR Expression by RNA Elongation Enhancement in Cancer

10.1101/812776 ◽

2019 ◽

Author(s):

Chi Hin Wong ◽

Chi Han Li ◽

Qifang He ◽

Joanna Hung Man Tong ◽

Ka-Fai To ◽

...

Keyword(s):

Dna Methylation ◽

Cancer Progression ◽

Positive Feedback ◽

Feedback Loop ◽

Transcription Elongation ◽

Underlying Mechanism ◽

Transcriptional Elongation ◽

Gene Body ◽

Gene Body Methylation ◽

Positive Feedback Loop

SUMMARYLong non-coding RNA HOX Transcript Antisense RNA (HOTAIR) is overexpressed in multiple cancers with diverse genetic profiles, which heavily contributed to cancer progression. However, the underlying mechanism leading to HOTAIR deregulation is largely unexplored. Here, we revealed that gene body methylation promoted HOTAIR expression through enhancing the transcription elongation process in cancer. We linked up the aberrant gene body histone and DNA methylation in promoting transcription elongation via phosphorylation of Polymerase II Ser 2 by CDK7-CDK9, and elucidated the mechanism of a positive feedback loop involving CDK7, MLL1 and DNMT3A in promoting gene body methylation and overexpressing HOTAIR. To our knowledge, this is the first time to demonstrate that a positive feedback loop that involved CDK9-mediated phosphorylation of PolII and histone and gene body methylation induced robust transcriptional elongation, which heavily contributed to the upregulation of oncogenic lncRNA in cancer.

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