Glutamate metabotropic receptor 4 (GRM4) inhibits cell proliferation, migration and invasion in breast cancer and is regulated by miR-328-3p and miR-370-3p

Xiao, Bin; Chen, Daxiang; Zhou, Quan; Hang, Jianfeng; Zhang, Weiyun; Kuang, Zhenzhan; Sun, Zhigang; Li, Linhai

doi:10.1186/s12885-019-6068-4

Cited by 38 publications

(34 citation statements)

References 23 publications

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“…EVs are a class of membranous vesicles, including microvesicles and exosomes that are essential for the intercellular communication in extensive pathological processes 8 . microRNAs (miRNAs) are abundant cargos in EVs, which may have relation to the migration ability and invasion ability of breast cancer 9,10 . Accumulating studies have expounded on the causal relationship between the expression of miR‐370‐3p and breast cancer.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐370‐3p shuttled by breast cancer cell‐derived extracellular vesicles induces fibroblast activation through the CYLD/Nf‐κB axis to promote breast cancer progression

Ren

Lv²,

et al. 2021

FASEB j.

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Breast cancer is a malignancy arising in the mammary epithelial tissues. Recent studies have indicated the abundance of microRNAs (miRNAs) in extracellular vesicles (EVs), and their interactions have been illustrated to exert crucial roles in the cell‐to‐cell communication. The present study focused on investigating whether EV‐delivered miR‐370‐3p affects breast cancer. Initially, the miR‐370‐3p expression pattern was examined in the cancer‐associated fibroblasts (CAFs), normal fibroblasts (NFs), and cancerous cells‐derived EVs. The relation of miR‐370‐3p to CYLD was assessed using luciferase activity assay. Afterwards, based on ectopic expression and depletion experiments in the MCF‐7 breast cancer cells, we evaluated stemness, migration, invasion, and sphere formation ability, and EMT, accompanied with measurement on the expression patterns of pro‐inflammatory factors and nuclear factor‐kappa B (NF‐κB) signaling‐related genes. Finally, tumorigenesis and proliferation were analyzed in vivo using a nude mouse xenograft model. The in vitro experiments revealed that breast cancer cell‐derived EVs promoted NF activation, while activated fibroblasts contributed to enhanced stemness, migration, invasion, as well as EMT of cancerous cells. In addition, EVs could transfer miR‐370‐3p from breast cancer cells to NFs, and EV‐encapsulated miR‐370‐3p was also found to facilitate fibroblast activation. Mechanistically, EV‐encapsulated miR‐370‐3p downregulated the expression of CYLD through binding to its 3′UTR and activated the NF‐κB signaling pathway, thereby promoting the cellular functions in vitro and in vivo in breast cancer. Taken together, EVs secreted by breast cancer cells could carry miR‐370‐3p to aggravate breast cancer through downregulating CYLD expression and activating the NF‐κB signaling pathway.

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Section: Introductionmentioning

confidence: 99%

MicroRNA‐370‐3p shuttled by breast cancer cell‐derived extracellular vesicles induces fibroblast activation through the CYLD/Nf‐κB axis to promote breast cancer progression

Ren

Lv²,

et al. 2021

FASEB j.

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“…It was reported that miR-328 could function as an anti-oncogene, repress cell migration in gastric cancer cells (28) and in osteosarcoma cells (29). On the contrary, in breast cancer cells, elevated miR-328-3p could decrease the abundances of glutamate metabotropic receptor 4 (GRM4) and counteract GRM4induced inhibition of breast cancer cell migration and invasion (30). Notably, recent studies showed that miR-328a-3p might even lead to different cellular behaviors in endothelial cells exposed to diverse culture conditions.…”

Section: Discussionmentioning

confidence: 99%

miR-328a-3p stimulates endothelial cell migration and angiogenesis

Chen

zhang

Cai

et al. 2021

Preprint

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Background Endothelial cells play important biological roles after peripheral nerve injury by forming blood vessels within the nerve gap after peripheral nerve injury and guiding Schwann cell migration. microRNAs (miRNAs) affect cellular behavior and regulate a wide variety of physiological and pathological activities, including peripheral nerve regeneration. Emerging studies identified the essential roles of miRNAs on the phenotype modulation of Schwann cells while the effects of miRNAs on endothelial cells were not well investigated. miR-328a-3p was differentially expressed in peripheral nerve stumps after nerve injury. This study aimed to identify the biological effects of miR-328a-3p on human umbilical vein endothelial cells (HUVECs). Methods Here, the biological functions of miR-328a-3p on endothelial cells were determined by transfecting cultured human umbilical vein endothelial cells (HUVECs) with miR-328a-3p mimic or inhibitor. Heatmaps of lncRNAs and mRNAs were generated using meV software according to previous obtained sequencing data of sciatic nerve stumps at 0, 1, 4, 7, and 14 days after nerve crush injury. Results Transfection with miR-328a-3p mimic led to slightly decreased HUVEC proliferation and robustly increased HUVEC migration and tubulogenesis while transfection with miR-328a-3p mimic led to opposite observations. Bioinformatic analysis further discovered potential regulators and effectors of miR-328a-3p and constructed a miR-328a-3p-centered competing endogenous RNA (ceRNA) network. Conclusions Collectively, our present study demonstrated that dysregulated miR-328a-3p after peripheral nerve injury might affect the migration and angiogenesis of endothelial cells and contribute to peripheral nerve regeneration. Trial registration: The rats were obtained from the Experimental Animal Center of Nantong University (Animal licenses No. SCXK [Su] 2014-0001 and SYXK [Su] 2012-0031).

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“… 22 Moreover, Hou’s research had already indicated that miR-519d could bind to Ki-67 and involved in liver cancer suppression which was consistent with our results conducted in breast cancer cells. 15 On the other hand, focused on miR-328-3p, it owned tumor-suppressive function in breast cancer 9 and osteosarcoma 23 via targeting different molecules. In this research, we found that in breast cancer cells, miR-519d and miR-328-3p directly targeted Ki-67 to reduce its expression to suppress proliferation and block cell cycle progression and the anti-cancer effects of miR-519d were weaker than miR-328-3p which filled the research blank.…”

Section: Discussionmentioning

confidence: 99%

“… 8 MiR-328-3p targets GRM4 and suppresses metastasis of breast cancer. 9 Therefore, more targets of miR-519d and miR-328-3p needed to be identified and whether they could target a common target in the mediation of breast cancer need to be studied.…”

Section: Introductionmentioning

confidence: 99%

<p>MiR-519d and miR-328-3p Combinatorially Suppress Breast Cancer Progression</p>

Ma¹,

Liu²,

Xu³

et al. 2020

OTT

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Background MiR-519d and miR-328-3p had tumor-regulatory properties in different cancers, but their combinatorial effects and potential common target in breast cancer had not been fully reported. This research targeted to study the underlying mechanism of how miR-519d and miR-328-3p cooperatively suppressed breast cancer. Methods MiR-519d and miR-328-3p expressions in breast cancer tissues and cells were assessed and Ki-67 expression was also checked. DLR assay was executed to verify whether Ki-67 was a common target of miR-519d and miR-328-3p. Western blot, flow cytometry, colony formation, wound healing and transwell assays were applied to examine the inhibitory roles of these two miRNAs on the malignant behaviors of breast cancer cells and the potential molecular mechanism. Results Impeded miR-519d and miR-328-3p expressions and enhanced Ki-67 expression were detected in breast cancer tissues and cells. Ki-67 was confirmed as a target of these two miRNAs. MiR-519d and miR-328-3p hampered cell proliferation and blocked cell cycle via binding to Ki-67 and they also suppressed migration and invasion. The combinatorial effects of two miRNAs were much stronger than a single miRNA. Conclusion Our findings proved that miR-519d and miR-328-3p played combinatorial anti-cancer roles in breast cancer by directly targeting a common target Ki-67. Our study suggested that these two miRNAs might own the potential to become novel therapeutic biomarkers involved in the diagnosis and therapy of breast cancer.

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Glutamate metabotropic receptor 4 (GRM4) inhibits cell proliferation, migration and invasion in breast cancer and is regulated by miR-328-3p and miR-370-3p

Cited by 38 publications

References 23 publications

MicroRNA‐370‐3p shuttled by breast cancer cell‐derived extracellular vesicles induces fibroblast activation through the CYLD/Nf‐κB axis to promote breast cancer progression

MicroRNA‐370‐3p shuttled by breast cancer cell‐derived extracellular vesicles induces fibroblast activation through the CYLD/Nf‐κB axis to promote breast cancer progression

miR-328a-3p stimulates endothelial cell migration and angiogenesis

<p>MiR-519d and miR-328-3p Combinatorially Suppress Breast Cancer Progression</p>

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