Elastin-derived peptides stimulate trophoblast migration and invasion: a positive feedback loop to enhance spiral artery remodelling

AbstractEsophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in the digestive system with a high incidence and poor prognosis. Long non-coding RNAs (LncRNA) have been reported to be closely associated with the occurrence and development of various human cancers. Data from GSE89102 shows an increase of THAP9-AS1 expression in ESCC. However, its functions and mechanisms underlying ESCC progression remain to be investigated. In this study, we found that THAP9-AS1 was overexpressed in ESCC tissues and cells. High THAP9-AS1 expression was positively correlated with tumor size, TNM stage, lymph node metastasis, and worse prognosis. Functionally, depletion of THAP9-AS1 suppressed cell proliferation, migration, and invasion, while enhanced apoptosis in vitro. Consistently, knockdown of THAP9-AS1 inhibited xenograft tumor growth in vivo. Mechanistically, THAP9-AS1 could serve as a competing endogenous RNA (ceRNA) for miR-133b, resulting in the upregulation of SOX4. Reciprocally, SOX4 bound to the promoter region of THAP9-AS1 to activate its transcription. Moreover, the anti-tumor property induced by THAP9-AS1 knockdown was significantly impaired due to miR-133b downregulation or SOX4 overexpression. Taken together, our study reveals a positive feedback loop of THAP9-AS1/miR-133b/SOX4 to facilitate ESCC progression, providing a potential molecular target to fight against ESCC.

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A positive feedback loop between HER2 and ADAM12 in human head and neck cancer cells increases migration and invasion

Oncogene ◽

10.1038/onc.2011.460 ◽

2011 ◽

Vol 31 (23) ◽

pp. 2888-2898 ◽

Cited By ~ 27

Author(s):

V H Rao ◽

A Kandel ◽

D Lynch ◽

Z Pena ◽

N Marwaha ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Cancer Cells ◽

Neck Cancer ◽

Positive Feedback ◽

Feedback Loop ◽

Human Head ◽

Migration And Invasion ◽

Positive Feedback Loop

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The positive feedback loop of RNASEH1-AS1/has-miR-218-5p/NET1 mediated by POU2F1 contributes to the development and progression of human lung squamous carcinoma

10.21203/rs.3.rs-18125/v1 ◽

2020 ◽

Author(s):

Jing-hao Jia ◽

Jing Wang ◽

Jia-rui Yu ◽

Peng Gao ◽

Yan-kun Liu ◽

...

Keyword(s):

Positive Feedback ◽

Feedback Loop ◽

Human Lung ◽

Squamous Carcinoma ◽

Carcinoma Cells ◽

Human Lung Cancer ◽

Migration And Invasion ◽

Positive Feedback Loop ◽

Squamous Carcinoma Cells ◽

Lung Squamous Carcinoma

Abstract Background In molecular level, competing endogenous RNAs (ceRNAs) regulates other RNA transcripts through competing for shared microRNAs (miRNA). miRNA negatively regulate gene expression at the levels of mRNAs stability and translation suppression. Methods We tested the mRNA level of miR-218-5p and RNASEH1-AS1 in clinical lung squamous cell carcinoma tissues by qRT-PCR. In the exploring of the role of miR-218-5p and RNASEH1-AS1 in the malignant phenotype of NCI-H520 cells, colony formation and MTT assay were used to test the cell viability and proliferation capability, trans-well invasion and wound healing assay were performed to examine the cell migration and invasion. ChIP assay was conducted to confirm the direct interact of POU2F1 and RNASEH1-AS1 promoter. Results In this investigation, we found that LncRNA RNASEH1-AS1 is up-regulated in human lung cancer, and serves as a miRNA sponge for hsa-miR-218-5p in human lung squamous carcinoma cells. lncRNA RNASEH1-AS1 facilitates growth and motility of lung squamous carcinoma cells, while miR-218-5p does the opposite. NET1 and POU2F1 are validated as direct and functional targets of miR-218-5p. The downregulation of miR-218-5p releases the suppression of NET1 and POU2F1. POU2F1 binds directly to the lncRNA-RNASEH1-AS1 promoter and acts as transcription factor to enhance the promoter activity of RNASEH1-AS1. Conclusion Above all, the positive feedback loop of RNASEH1-AS1/ hsa-miR-218-5p/ NET1/ POU2F1 can help us to understand the regulatory mechanism behind genesis and progression of human lung squamous carcinoma, possibly providing new biomarkers for its diagnosis and treatment.

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Positive feedback loop of HMGB1 and tumor-associated macrophages plays a key role in osteosarcoma metastasis

10.21203/rs.3.rs-1185816/v1 ◽

2021 ◽

Author(s):

Changhe Hou ◽

Ming Lu ◽

Zixiong Lei ◽

Shuangwu Dai ◽

Wei Chen ◽

...

Keyword(s):

Positive Feedback ◽

Feedback Loop ◽

Macrophage Polarization ◽

Migration And Invasion ◽

M2 Macrophages ◽

Osteosarcoma Cells ◽

Invasion And Metastasis ◽

Tumor Associated Macrophages ◽

Positive Feedback Loop ◽

Hmgb1 Expression

Abstract Background Numerous studies have demonstrated the important roles of tumor-associated macrophages (TAMs) in osteosarcoma metastasis. In osteosarcoma, higher levels of HMGB1 correlate with osteosarcoma progression. However, whether HMGB1 is involved in the polarization of M2 macrophages into M1 macrophages in osteosarcoma still remains largely unknown. Methods HMGB1 and CD206 mRNA expression was measured by qRT-PCR in osteosarcoma tissues and cells. HMGB1 and RAGE protein expression was measured by western blotting. Osteosarcoma migration was measured using a Transwell and wound-healing assay. Osteosarcoma invasion was measured using a Transwell assay. Macrophage subtypes were detected using flow cytometry. Results HMGB1 is aberrantly overexpressed in osteosarcoma, and positively correlates with the TNM III & IV stages, lymph node metastasis, and distant metastasis. Silencing HMGB1 inhibits migration, invasion, and metastasis-related proteins in osteosarcoma cells. Furthermore, the reduced HMGB1 expression in the conditioned media derived from osteosarcoma cells also induces the polarization of M2 TAMs to M1 TAMs. In addition, silencing HMGB1 inhibits the liver and lung metastases of osteosarcoma and reduces the expression of HMGB1, CD163, and CD206 in vivo experiments. HMGB1 regulates macrophage polarization through RAGE. Interestingly, the polarized M2 macrophages could induce osteosarcoma migration and invasion, which in turn results in activation of HMGB1 expression in osteosarcoma cells to form a positive feedback loop. Conclusions HMGB1 and M2 macrophages enhance osteosarcoma migration, invasion, and metastasis capability through positive feedback regulation. These findings reveal the significance of tumor cell and TAM interaction in the metastatic microenvironment.

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A novel long non‑coding RNA TTN‑AS1/microRNA‑589‑5p/FOXP1 positive feedback loop increases the proliferation, migration and invasion of pancreatic cancer cell lines

Oncology Letters ◽

10.3892/ol.2021.13055 ◽

2021 ◽

Vol 22 (5) ◽

Author(s):

Jing Zhao ◽

Fang Wu ◽

Jun Yang

Keyword(s):

Pancreatic Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Positive Feedback ◽

Feedback Loop ◽

Pancreatic Cancer Cell ◽

Migration And Invasion ◽

Positive Feedback Loop ◽

Non Coding Rna ◽

Long Non Coding Rna

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ITGB1-DT Facilitates Lung Adenocarcinoma Progression via Forming a Positive Feedback Loop With ITGB1/Wnt/β-Catenin/MYC

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.631259 ◽

2021 ◽

Vol 9 ◽

Author(s):

Ruimin Chang ◽

Xiaoxiong Xiao ◽

Yao Fu ◽

Chunfang Zhang ◽

Xiaoyan Zhu ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Positive Feedback ◽

Feedback Loop ◽

Cellular Proliferation ◽

Disease Free Survival ◽

Migration And Invasion ◽

Poor Overall Survival ◽

Positive Feedback Loop ◽

Downstream Target

Lung adenocarcinoma (LUAD) is the main histological type of lung cancer, which is the leading cause of cancer-related deaths. Long non-coding RNAs (lncRNAs) were recently revealed to be involved in various cancers. However, the clinical relevance and potential biological roles of most lncRNAs in LUAD remain unclear. Here, we identified a prognosis-related lncRNA ITGB1-DT in LUAD. ITGB1-DT was upregulated in LUAD and high expression of ITGB1-DT was correlated with advanced clinical stages and poor overall survival and disease-free survival. Enhanced expression of ITGB1-DT facilitated LUAD cellular proliferation, migration, and invasion, and also lung metastasis in vivo. Knockdown of ITGB1-DT repressed LUAD cellular proliferation, migration, and invasion. ITGB1-DT interacted with EZH2, repressed the binding of EZH2 to ITGB1 promoter, reduced H3K27me3 levels at ITGB1 promoter region, and therefore activated ITGB1 expression. Through upregulating ITGB1, ITGB1-DT activated Wnt/β-catenin pathway and its downstream target MYC in LUAD. The expressions of ITGB1-DT, ITGB1, and MYC were positively correlated with each other in LUAD tissues. Intriguingly, ITGB1-DT was found as a transcriptional target of MYC. MYC directly transcriptionally activated ITGB1-DT expression. Thus, ITGB1-DT formed a positive feedback loop with ITGB1/Wnt/β-catenin/MYC. The oncogenic roles of ITGB1-DT were reversed by depletion of ITGB1 or inhibition of Wnt/β-catenin pathway. In summary, these findings revealed ITGB1-DT as a prognosis-related and oncogenic lncRNA in LUAD via activating the ITGB1-DT/ITGB1/Wnt/β-catenin/MYC positive feedback loop. These results implicated ITGB1-DT as a potential prognostic biomarker and therapeutic target for LUAD.

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Identification of a TGF-β/SMAD/lnc-UTGF positive feedback loop and its role in hepatoma metastasis

Signal Transduction and Targeted Therapy ◽

10.1038/s41392-021-00781-3 ◽

2021 ◽

Vol 6 (1) ◽

Author(s):

Meng-Zhi Wu ◽

Yi-chuan Yuan ◽

Bi-Yu Huang ◽

Jin-Xi Chen ◽

Bin-Kui Li ◽

...

Keyword(s):

Positive Feedback ◽

Feedback Loop ◽

Ectopic Expression ◽

Migration And Invasion ◽

Loss Of Function ◽

Positive Feedback Loop ◽

Free Survival ◽

Smad Signaling ◽

Smad Signaling Pathway

AbstractAberrant activation of the TGF-β/SMAD signaling pathway is often observed in hepatocellular carcinoma (HCC). Whether lncRNA regulates the TGF-β/SMAD signaling remains largely unknown. Here, we identified an oncogenic lncRNA that was upregulated in HCC and was transcriptionally induced by TGF-β (named lnc-UTGF, lncRNA upregulated by TGF-β). Upon TGF-β stimulation, SMAD2/3 bound to the lnc-UTGF promoter and activated lnc-UTGF expression. In turn, the TGF-β/SMAD signaling was augmented by overexpressing lnc-UTGF, but was inhibited by silencing lnc-UTGF. Mechanism investigations revealed that lnc-UTGF interacted with the mRNAs of SMAD2 and SMAD4 via complementary base-pairing, resulting in enhanced stability of SMAD2/4 mRNAs. These data suggest a novel TGF-β/SMAD/lnc-UTGF positive feedback circuitry. Subsequent gain- and loss-of-function analyses disclosed that lnc-UTGF promoted the migration and invasion of hepatoma cells, and this effect of lnc-UTGF was attenuated by repressing SMAD2/4 expression or by mutating the SMAD2/4-binding sites in lnc-UTGF. Studies using mouse models further confirmed that in vivo metastasis of hepatoma xenografts was inhibited by silencing lnc-UTGF, but was enhanced by ectopic expression of lnc-UTGF. The lnc-UTGF level was positively correlated with the SMAD2/4 levels in xenografts. Consistently, we detected an association of lnc-UTGF upregulation with increase of SMAD2, SMAD4, and their metastasis effector SNAIL1 in human HCC. And high lnc-UTGF level was also significantly associated with enhanced metastasis potential, advanced TNM stages, and worse recurrence-free survival. Conclusion: there exists a lnc-UTGF-mediated positive feedback loop of the TGF-β signaling and its deregulation promotes hepatoma metastasis. These findings may provide a new therapeutic target for HCC metastasis.

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