circPTCH1 promotes invasion and metastasis in renal cell carcinoma via regulating miR-485-5p/MMP14 axis

Liu, Huan; Hu, Guanghui; Wang, Zaoyu; Liu, Qunlong; Zhang, Jin; Chen, Yonghui; Huang, Yiran; Xue, Wei; Xu, Yunfei; Zhai, Wei

doi:10.7150/thno.47239

Cited by 64 publications

(37 citation statements)

References 52 publications

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“…Based on accumulating evidence, the most explored function of circRNAs is regulating gene expression through ´sponging´ other gene expression regulators, in particular miRNA 33 . For example, circPTCH1 could act as a sponge for miR-485-5p to promote invasion and metastasis in renal cell carcinoma 34 . Hsa_circ_0000326 interacted with miR-338-3p to facilitate lung adenocarcinoma progression 35 .…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circBCBM1 promotes breast cancer brain metastasis by modulating miR-125a/BRD4 axis

Fu¹,

Liu²,

Zhu³

et al. 2021

Int. J. Biol. Sci.

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Circular RNAs (circRNAs) play critical roles in tumorigenesis and the progression of various cancers. We previously identified a novel upregulated circRNA, circBCBM1 (hsa_circ_0001944), in the context of breast cancer brain metastasis. However, the potential biological function and molecular mechanism of circBCBM1 in breast cancer brain metastasis remain largely unknown. In this study, we confirmed that circBCBM1 was a stable and cytoplasmic circRNA. Functionally, circBCBM1 promoted the proliferation and migration of 231-BR cells in vitro and growth and brain metastasis in vivo . Mechanistically, circBCBM1 acted as an endogenous miR-125a sponge to inhibit miR-125a activity, resulting in the upregulation of BRD4 (bromodomain containing 4) and subsequent upregulation of MMP9 (matrix metallopeptidase 9) through Sonic hedgehog (SHH) signaling pathway. Importantly, circBCBM1 was markedly upregulated in the breast cancer brain metastasis cells and clinical tissue and plasma samples; besides, circBCBM1 overexpression in primary cancerous tissues was associated with shorter brain metastasis-free survival (BMFS) of breast cancer patients. These findings indicate that circBCBM1 is involved in breast cancer brain metastasis via circBCBM1/miR-125a/BRD4 axis. CircBCBM1 may serve as a novel diagnostic and prognostic biomarker and potential therapeutic target for breast cancer brain metastasis.

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Section: Discussionmentioning

confidence: 99%

Circular RNA circBCBM1 promotes breast cancer brain metastasis by modulating miR-125a/BRD4 axis

Fu¹,

Liu²,

Zhu³

et al. 2021

Int. J. Biol. Sci.

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“…It showed that AhR expression was abnormally increased in RCC. RCC was often accompanied by EMT conversion ( 16 ). We next detected the expression of E-cadherin, N-cadherin, and Vimentin related to EMT.…”

Section: Resultsmentioning

confidence: 99%

“…It showed that AhR expression was abnormally increased in RCC. RCC was often accompanied by EMT conversion (16). We next detected the 1C,D).…”

Section: High Expression Of Ahr In Rcc Tissuesmentioning

confidence: 93%

The Gut Microbiota Activates AhR Through the Tryptophan Metabolite Kyn to Mediate Renal Cell Carcinoma Metastasis

Dai

Chen

2021

Front. Nutr.

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Background: The incidence of renal cell carcinoma (RCC) is increasing year by year. It is difficult to have complete treatment so far. Studies have shown that tryptophan metabolite Kynurenine (Kyn) affects cell proliferation, migration, apoptosis, adhesion, and differentiation. Our aim is to explore whether Kyn activates aromatic hydrocarbon receptor (AhR) to mediate RCC metastasis.Methods: We collected RCC tissues and feces from RCC patients. 16S rRNA technology was performed to analyze the gut microbial composition of RCC patients. LC-MS/MS was used to analyze the gut microbial metabolites. The AhR was inhibited and treated with Kyn. Immunofluorescence was used to measure the degree of AhR activation. The migration and invasion ability of 786-O cells was tested by Transwell assay. Flow cytometry and cell cycle assay were utilized to observe the apoptosis and cycle of 786-O cells. CCK-8 assay was used to detect 786-O cells proliferation. qRT-PCR and Western blot were used to detect AhR and EMT-related genes expression level.Results: AhR expression was up-regulated in RCC tissues. RCC gut microbiota was disordered. The proportion of Kyn was increased in RCC. After being treated with Kyn, the migration, invasion, and proliferation ability of 786-O cells were decreased. Furthermore, the expression of EMT-related protein E-cadherin decreased, and the expression of N-cadherin and Vimentin increased. The proportion of 786-O cells in the S phase increased. The apoptosis rate of 786-O cells was inhibited.Conclusion: The tryptophan metabolite Kyn could activate AhR. Kyn could promote 786-O cells migration and invasion. Gut microbiota could activate AhR through its tryptophan metabolite Kyn to mediate RCC metastasis.

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“…Based on accumulating evidence, the most explored function of circRNAs is regulating gene expression through ´sponge´ other gene expression regulators, in particular miRNA [32]. For example, circPTCH1 could act as sponge for miR-485-5p to promote invasion and metastasis in renal cell carcinoma [33].…”

Section: Discussionmentioning

confidence: 99%

CircBCBM1 Promotes Breast Cancer Brain Metastasis via miR-125a/BRD4 Axis

Liu

et al. 2020

Preprint

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Background: Accumulating evidence indicates that circular RNAs (circRNAs) play critical roles in tumorigenesis and progression of various cancers. We previously identified a novel upregulated circRNA, circBCBM1 (hsa_circ_0001944), in the context of breast cancer brain metastasis. However, the potential biological function and molecular mechanism of circBCBM1 in breast cancer brain metastasis remain largely unknown.Methods: In this reserch, we validated the expression and characterization of circBCBM1 through RT-qPCR, Sanger sequencing, RNase R assay and fluorescence in situ hybridization (FISH). Functional experiments were performed to determine the effect of circBCBM1 on growth and metastasis of 231-BR cells both in vitro and in vivo. The regulatory mechanisms among circBCBM1, miR-125a (has-miR-125a-5p), and BRD4 (bromodomain containing 4) were investigated by RNA immunoprecipitation (RIP), RNA pull-down, luciferase reporter assay and western blot. Results: Our findings demonstrated that circBCBM1 is a stable and cytoplasmic circRNA. Functionally, silencing of circBCBM1 led to decreased proliferation and migration of 231-BR cells whereas elevated circBCBM1 expression showed reverse effects in vitro. These findings were confirmed in vivo in mouse models, as knockdown of circBCBM1 significantly decreased growth and brain metastases of 231-BR cells. Mechanistically, circBCBM1 functions as an endogenous miR-125a sponge to inhibit miR-125a activity, resulting in the upregulation of BRD4 expression and subsequent upregulation of MMP9 (matrix metallopeptidase 9) through Sonic hedgehog (SHH) signaling pathway. Importantly, circBCBM1 was markedly upregulated in the breast cancer brain metastasis cells and clinical tissue and plasma samples; besides, the overexpression of circBCBM1 in primary cancerous tissues was associated with shorter brain metastasis-free survival (BMFS) of breast cancer patients.Conclusions: These findings indicate that circBCBM1 is involved in breast cancer brain metastasis via circBCBM1/miR-125a/BRD4 axis, which sheds light on the pathogenic mechanism of circBCBM1 and provides translational evidence that circBCBM1 may serve as a novel diagnostic or prognostic biomarker and potential therapeutic target for breast cancer brain metastasis.

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circPTCH1 promotes invasion and metastasis in renal cell carcinoma via regulating miR-485-5p/MMP14 axis

Cited by 64 publications

References 52 publications

Circular RNA circBCBM1 promotes breast cancer brain metastasis by modulating miR-125a/BRD4 axis

Circular RNA circBCBM1 promotes breast cancer brain metastasis by modulating miR-125a/BRD4 axis

The Gut Microbiota Activates AhR Through the Tryptophan Metabolite Kyn to Mediate Renal Cell Carcinoma Metastasis

CircBCBM1 Promotes Breast Cancer Brain Metastasis via miR-125a/BRD4 Axis

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