Long noncoding RNA HEGBC promotes tumorigenesis and metastasis of gallbladder cancer via forming a positive feedback loop with IL-11/STAT3 signaling pathway

The long noncoding RNA (lncRNA) LINC00152, also known as CYTOR, displays aberrant expression in various cancers. However, its clinical value and functional mechanisms in breast cancer remain insufficiently understood. Our study found that LINC00152 is significantly upregulated in breast cancer, and that it acts as an indicator of poor survival prognosis. Further studies revealed that LINC00152 knockdown suppresses cell proliferation and tumorigenicity in vitro and in vivo. Mechanistic analyses demonstrated that LINC00152 directly binds to KLF5 protein and increases KLF5 stability. Moreover, LINC00152 is also a KLF5-responsive lncRNA, and KLF5 activates LINC00152 transcription by directly binding to its promoter. Our study suggests that LINC00152 promotes tumor progression by interacting with KLF5. LINC00152 may be a valuable prognostic predictor for breast cancer, and the positive feedback loop of LINC00152-KLF5 could be a therapeutic target in pharmacological strategies.

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Long noncoding RNA LINC01578 drives colon cancer metastasis through a positive feedback loop with the NF‐κB/YY1 axis

Molecular Oncology ◽

10.1002/1878-0261.12819 ◽

2020 ◽

Vol 14 (12) ◽

pp. 3211-3233 ◽

Cited By ~ 1

Author(s):

Jia Liu ◽

Yang Zhan ◽

Jiefu Wang ◽

Junfeng Wang ◽

Jiansheng Guo ◽

...

Keyword(s):

Colon Cancer ◽

Positive Feedback ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Feedback Loop ◽

Cancer Metastasis ◽

Positive Feedback Loop ◽

Colon Cancer Metastasis

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LGR6 activates the Wnt/β-catenin signaling pathway and forms a β-catenin/TCF7L2/LGR6 feedback loop in LGR6high cervical cancer stem cells

Oncogene ◽

10.1038/s41388-021-02002-1 ◽

2021 ◽

Author(s):

Qian Feng ◽

Shan Li ◽

Hong-Mei Ma ◽

Wen-Ting Yang ◽

Peng-Sheng Zheng

Keyword(s):

Cervical Cancer ◽

Stem Cells ◽

Cancer Stem Cells ◽

Wnt Signaling ◽

Signaling Pathway ◽

Western Blotting ◽

Positive Feedback ◽

Feedback Loop ◽

Stem Cell Marker ◽

Positive Feedback Loop

AbstractThe leucine-rich repeat-containing G-protein-coupled receptor 6 (LGR6) is considered to be a stem cell marker in many normal tissues and promotes tissue development, regeneration, and repair. LGR6 is also related to the initiation and progression of some malignant tumors. However, the role of LGR6 in cervical cancer has not been reported. Here, immunohistochemistry and western blotting showed that LGR6 was significantly upregulated in cervical cancer, compared with the normal cervix. By analyzing The Cancer Genome Atlas database, LGR6 was found to be correlated with a poor prognosis of cervical cancer. Then, a small population of LGR6high cells isolated by using the fluorescence-activated cell sorting exhibited enhanced properties of cancer stem cells including self-renewal, differentiation, and tumorigenicity. Moreover, RNA sequencing revealed that LGR6 was correlated with the Wnt signaling pathway and TOP/FOP, reverse transcription-PCR, and western blotting further proved that LGR6 could activate the Wnt/β-catenin signaling pathway. Interestingly, LGR6 upregulated the expression of TCF7L2 by activating the Wnt/β-catenin pathway. Then, TCF7L2 combining with β-catenin in the nucleus enhanced LGR6 transcription by binding the promoter of LGR6, which further activated the Wnt signaling to form a positive feedback loop. Thus, our study demonstrated that LGR6 activated a novel β-catenin/TCF7L2/LGR6-positive feedback loop in LGR6high cervical cancer stem cells (CSCs), which provided a new therapeutic strategy for targeting cervical CSCs to improve the prognosis of cervical cancer patients.

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Glycochenodeoxycholate promotes the metastasis of gallbladder cancer cells by inducing epithelial to mesenchymal transition via activation of SOCS3/JAK2/STAT3 signaling pathway

Journal of Cellular Physiology ◽

10.1002/jcp.29080 ◽

2019 ◽

Vol 235 (2) ◽

pp. 1615-1623

Author(s):

Hui Wang ◽

Ming Zhan ◽

Qiang Liu ◽

Jian Wang

Keyword(s):

Gallbladder Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Epithelial To Mesenchymal Transition ◽

Mesenchymal Transition ◽

Stat3 Signaling ◽

Stat3 Signaling Pathway

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Erratum for: Long Noncoding RNA HOST2 Promotes Epithelial- Mesenchymal Transition, Proliferation, Invasion and Migration of Hepatocellular Carcinoma Cells by Activating the JAK2-STAT3 Signaling Pathway

Cellular Physiology and Biochemistry ◽

10.33594/000000259 ◽

2020 ◽

Vol 54 (4) ◽

pp. 797-797

Keyword(s):

Hepatocellular Carcinoma ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Epithelial Mesenchymal Transition ◽

Carcinoma Cells ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

Stat3 Signaling ◽

Stat3 Signaling Pathway ◽

And Migration

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An HGF-dependent positive feedback loop between bladder cancer cells and fibroblasts mediates lymphangiogenesis and lymphatic metastasis

10.21203/rs.3.rs-1104668/v1 ◽

2021 ◽

Author(s):

Changhao Chen ◽

Yuting Li ◽

Yuming Luo ◽

Hanhao Zheng ◽

Yan Lin ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Cells ◽

Positive Feedback ◽

Noncoding Rna ◽

Feedback Loop ◽

Xenograft Model ◽

Positive Feedback Loop ◽

Reciprocal Interactions ◽

Orthotopic Xenograft Model ◽

Bladder Cancer Cells

Abstract Cancer-associated fibroblasts (CAFs) are essential etiologic actors in promoting tumor progression via extensive reciprocal interactions with cancer cells. Yet, the biological role and regulatory mechanism of CAFs phenotype underlying lymph node (LN) metastasis of bladder cancer (BCa) remain unclear. Here, we report that BCa cell-secreted extracellular vesicles (EVs) played an important role in the CAF-enriched microenvironment, which correlated with BCa lymphangiogenesis and LN metastasis. RNA sequencing identified an EV-associated long noncoding RNA, LINC00665, which acted as a crucial mediator of CAF infiltration in BCa. LINC00665 mediated EV release from BCa cells to endow fibroblasts with the CAF phenotype, which reciprocally induced LINC00665 upregulation to form a RAB27B-HGF-c-Myc positive feedback loop, facilitating BCa lymphangiogenesis and LN metastasis. Importantly, we demonstrate that Cabozantinib significantly suppressed LINC00665-mediated BCa LN metastasis in an orthotopic xenograft model. Our study highlights a molecular mechanism by which LINC00665 induces a RAB27B-HGF-c-Myc positive feedback loop between cancer cells and fibroblasts to sustain BCa LN metastasis, and represents LINC00665 as a potential therapeutic target in BCa LN metastasis.

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APP/PS1 Gene-Environment Noise Interaction Aggravates AD-like Neuropathology in Hippocampus Via Activation of the VDAC1 Positive Feedback Loop

Current Alzheimer Research ◽

10.2174/1567205018666210324114153 ◽

2021 ◽

Vol 18 (1) ◽

pp. 14-24

Author(s):

Huimin Chi ◽

Qingfeng Zhai ◽

Ming Zhang ◽

Donghong Su ◽

Wa Cao ◽

...

Keyword(s):

Signaling Pathway ◽

Positive Feedback ◽

Feedback Loop ◽

Noise Exposure ◽

Glycogen Synthase ◽

Amyloid Β ◽

Environmental Noise ◽

Voltage Dependent Anion Channel ◽

Positive Feedback Loop ◽

The Impact

Background: Environmental risk factors, including environmental noise stress, and genetic factors, have been associated with the occurrence and development of Alzheimer’s disease (AD). However, the exact role and mechanism of AD-like pathology induced by environment-gene interactions between environmental noise and APP/PS1 gene remain elusive. Methods: Herein, we investigated the impact of chronic noise exposure on AD-like neuropathology in APP/PS1 transgenic mice. The Morris water maze (MWM) task was conducted to evaluate AD-like changes. The hippocampal phosphorylated Tau, amyloid-β (Aβ), and neuroinflammation were assessed. We also assessed changes in positive feedback loop signaling of the voltage-dependent anion channel 1 (VDAC1) to explore the potential underlying mechanism linking AD-like neuropathology to noise-APP/PS1 interactions. Results: Long-term noise exposure significantly increased the escape latency and the number of platform crossings in the MWM task. The Aβ overproduction was induced in the hippocampus of APP/PS1 mice, along with the increase of Tau phosphorylation at Ser396 and Thr231 and the increase of the microglia and astrocytes markers expression. Moreover, the VDAC1-AKT (protein kinase B)-GSK3β (glycogen synthase kinase 3 beta)-VDAC1 signaling pathway was abnormally activated in the hippocampus of APP/PS1 mice after noise exposure. Conclusion: Chronic noise exposure and APP/PS1 overexpression may synergistically exacerbate cognitive impairment and neuropathological changes that occur in AD. This interaction may be mediated by the positive feedback loop of the VDAC1-AKT-GSK3β-VDAC1 signaling pathway.

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