Gap Junctions Enhance the Antiproliferative Effect of MicroRNA‐124‐3p in Glioblastoma Cells

Zhang, Suzhi; Tao, Liang; Peng, Yuexia; Liu, Lucy; Hong, Xin; Zhang, Yuan; Wang, Qin

doi:10.1002/jcp.24982

Cited by 46 publications

(38 citation statements)

References 65 publications

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“…Mesenchymal stem cells were shown to transfer miR‐124 and miR‐145 mimics to cocultured glioma U87 cells through gap junctions, decreasing the migration and self‐renewal of glioma U87 cells . In our previous study, we also confirmed that in glioma U87 cells, gap junctions delivered miR‐124‐3p and augmented its antitumor effect . These findings suggest that gap junctions can transmit miRNA.…”

Section: Introductionsupporting

confidence: 73%

Pattern of cell‐to‐cell transfer of microRNA by gap junction and its effect on the proliferation of glioma cells

et al. 2019

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Micro RNA is expected to be a novel therapeutic tool for tumors. Gap junctions facilitate the transfer of micro RNA , which exerts biological effects on tumor cells. However, the length of micro RNA that can pass through certain gap junctions composed of specific connexin remains unknown. To address this question, the present study investigated the permeability of gap junctions composed of various connexins, including connexin 43, connexin 32 or connexin 37, to micro RNA s consisting of 18‐27 nucleotides in glioma cells and cervical cancer cells. Results indicated that all of the micro RNA s were able to be transferred from donor glioma cells to neighboring cells through the connexin 43 composed gap junction, but not the gap junctions composed of connexin 32 or connexin 37, in cervical cancer cells. Downregulation of the function of gap junctions comprising connexin 43 by pharmacological inhibition and sh RNA significantly decreased the transfer of these micro RNA s. In contrast, gap junction enhancers and overexpression of connexin 43 effectively increased these transfers. In glioma cells, cell proliferation was inhibited by micro RNA ‐34a. Additionally, these effects of micro RNA ‐34a were significantly enhanced by overexpression of connexin 43 in U251 cells, indicating that gap junctions play an important role in the antitumor effect of micro RNA by transfer of micro RNA to neighboring cells. Our data are the first to clarify the pattern of micro RNA transmission through gap junctions and provide novel insights to show that antitumor micro RNA s should be combined with connexin 43 or a connexin 43 enhancer, not connexin 32 or connexin 37, in order to improve the therapeutic effect.

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Section: Introductionsupporting

confidence: 73%

Pattern of cell‐to‐cell transfer of microRNA by gap junction and its effect on the proliferation of glioma cells

et al. 2019

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“…It also inhibits tumor progression by counteracting pro‐survival stress responses in GBM . The antitumor effect of miR‐124‐3p in GBM cells is enhanced through gap junctions by partly decreasing CDK6 expression . Furthermore, miR‐124‐3p is associated with malignant tumor progression and poor prognosis in glioma patients and is related to recurrent high‐grade gliomas in Mexican children, indicating that miR‐124‐3p is a potential biomarker for glioma.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐124‐3p regulates cell proliferation, invasion, apoptosis, and bioenergetics by targeting PIM1 in astrocytoma

Deng

Wang

Yao³

et al. 2016

Cancer Science

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The PIM1 protein is an important regulator of cell proliferation, the cell cycle, apoptosis, and metabolism in various human cancers. MicroRNAs (miRNAs) are powerful post‐transcriptional gene regulators that function through translational repression or transcript destabilization. Therefore, we aimed to identify whether a close relationship exists between PIM1 and miRNAs. PIM1 protein levels and mRNA levels were significantly upregulated in astrocytoma tissues, indicating the oncogenic role of PIM1 in astrocytoma. Further bioinformatics analysis indicated that miR‐124‐3p targeted the 3′‐UTR of PIM1. We also observed an inverse correlation between the miR‐124‐3p levels and PIM1 protein or mRNA levels in astrocytoma samples. Next, we experimentally confirmed that miR‐124‐3p directly recognizes the 3′‐UTR of the PIM1 transcript and regulates PIM1 expression at both the protein and mRNA levels. Furthermore, we examined the biological consequences of miR‐124‐3p targeting PIM1 in vitro. We showed that the repression of PIM1 in astrocytoma cancer cells by miR‐124‐3p suppressed proliferation, invasion, and aerobic glycolysis and promoted apoptosis. We observed that the restoration or inhibition of PIM1 activity resulted in effects that were similar to those induced by miR‐124‐3p inhibitors or mimics in cancer cells. Finally, overexpression of PIM1 rescued the inhibitory effects of miR‐124‐3p. In summary, these findings aid in understanding the tumor‐suppressive role of miR‐124‐3p in astrocytoma pathogenesis through the inhibition of PIM1 translation.

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“…More recently, miRNA transfer from glioma cells to astrocytes was shown to enhance the glioma pro-invasive potential 133 . In contrast, gap junction-mediated miRNA transfer between miR-124-3p transfected and non-transfected glioma cells had anti-proliferative effects, demonstrating a miRNA-mediated “bystander effect” 187 . Subsequently, several miRNAs associated with survival and chemotherapy-resistance were suggested to pass through gap junctions formed between astrocytes and lung tumour cells in vitro 188 .…”

Section: Reassessing Connexins In Cancermentioning

confidence: 89%

Gap junctions and cancer: communicating for 50 years

et al. 2016

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Fifty years ago, tumour cells were found to lack electrical coupling, leading to the hypothesis that loss of direct intercellular communication is commonly associated with cancer onset and progression. Subsequent studies linked this phenomenon to gap junctions composed of connexin proteins. While many studies support the notion that connexins are tumour suppressors, recent evidence suggests that, in some tumour types, they may facilitate specific stages of tumour progression through both junctional and non-junctional signalling pathways. This Timeline article highlights the milestones connecting gap junctions to cancer, and underscores important unanswered questions, controversies and therapeutic opportunities in the field.

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Gap Junctions Enhance the Antiproliferative Effect of MicroRNA‐124‐3p in Glioblastoma Cells

Cited by 46 publications

References 65 publications

Pattern of cell‐to‐cell transfer of microRNA by gap junction and its effect on the proliferation of glioma cells

Pattern of cell‐to‐cell transfer of microRNA by gap junction and its effect on the proliferation of glioma cells

MicroRNA‐124‐3p regulates cell proliferation, invasion, apoptosis, and bioenergetics by targeting PIM1 in astrocytoma

Gap junctions and cancer: communicating for 50 years

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