Exosomal microRNA miR-1246 induces cell motility and invasion through the regulation of DENND2D in oral squamous cell carcinoma

Sakha, Sujata; Muramatsu, Tomoki; Ueda, Koji; Inazawa, Johji

doi:10.1038/srep38750

Cited by 163 publications

(141 citation statements)

References 41 publications

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“…The expression changes of miRNAs passing through the immunoadsorption column shows the same tendency either using Immusorba or Selesorb. miR‐1246 has been implicated in oral squamous cell carcinoma, where its expression is upregulated in cancer cell‐derived exosomes . Additionally, miR‐1246 expression is reduced by activated B cells via AKT‐p53 signaling pathway in SLE.…”

Section: Discussionmentioning

confidence: 99%

Changes in the Expression of Circulating microRNAs in Systemic Lupus Erythematosus Patient Blood Plasma After Passing Through a Plasma Adsorption Membrane

et al. 2018

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MicroRNAs (miRNAs, miRs) are small non-coding RNAs that mainly function in the post-transcriptional regulation of genes. miRNA that is secreted outside of cells, and which circulates in the peripheral blood, is called circulating microRNA. Systemic lupus erythematosus (SLE) is a typical autoimmune connective tissue disease and is mainly treated with immunosuppressive drugs. Therapeutic apheresis is often used to eliminate autoantibodies and cytokines. We have previously shown that circulating miRNAs in the blood of patients with SLE can be separated and removed from the blood using a plasma separation membrane. In the present study, we further separated circulating miRNA from three SLE patient's blood plasma by passing it through a plasma adsorption membrane, and then measured changes in miRNA levels using miRNAs microarray chip. Although the levels of many miRNAs were unaffected after passage through the plasma adsorption membrane, expression of some miRNAs, including miR-1246, miR-4732-5p, and miR-6088 are declined.

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Section: Discussionmentioning

confidence: 99%

Changes in the Expression of Circulating microRNAs in Systemic Lupus Erythematosus Patient Blood Plasma After Passing Through a Plasma Adsorption Membrane

et al. 2018

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“…Additionally, exosomal microRNAs may endow recipient cells with resistance to chemotherapy. Among all miRNAs investigated, miR-1246 has drawn much attention and has been found to function as a proto-oncogene in lung and other cancers [4, 5]. Recently, it was reported that miR-1246 was strongly up-regulated in breast cancer [6].…”

Section: Introductionmentioning

confidence: 99%

Exosomal MicroRNA MiR-1246 Promotes Cell Proliferation, Invasion and Drug Resistance by Targeting CCNG2 in Breast Cancer

Zhao

Tang

et al. 2017

Cell Physiol Biochem

230

163

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Background/Aims: Treatment of breast cancer remains a clinical challenge. This study aims to validate exosomal microRNA-1246 (miR-1246) as a serum biomarker for breast cancer and understand the underlying mechanism in breast cancer progression. Methods: The expression levels of endogenous and exosomal miRNAs were examined by real time PCR, and the expression level of the target protein was detected by western blot. Scanning electron and confocal microscopy were used to characterize exosomes and to study their uptake and transfer. Luciferase reporter plasmids and its mutant were used to confirm direct targeting. Furthermore, the functional significance of exosomal miR-1246 was estimated by invasion assay and cell viability assay. Results: In this study, we demonstrate that exosomes carrying microRNA can be transferred among different cell lines through direct uptake. miR-1246 is highly expressed in metastatic breast cancer MDA-MB-231 cells compared to non-metastatic breast cancer cells or non-malignant breast cells. Moreover, miR-1246 can suppress the expression level of its target gene, Cyclin-G2 (CCNG2), indicating its functional significance. Finally, treatment with exosomes derived from MDA-MB-231 cells could enhance the viability, migration and chemotherapy resistance of non-malignant HMLE cells. Conclusions: Together, our results support an important role of exosomes and exosomal miRNAs in regulating breast tumor progression, which highlights their potential for applications in miRNA-based therapeutics.

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“…Bhagirath et al established that miR‐1246 may be a tumor repressor in aggressive prostate cancer that is released via sEV from tumor cells, causing its upregulated expression in body fluids . On the contrary, Sakha et al put forward an opposite view that sEV miR‐1246 stimulates cell motility as well as invasion through by regulating DENND2D in oral squamous cell carcinoma . Coincidentally, Yamada et al found that colorectal cancer cell‐derived microvesicles comprising microRNA‐1246 stimulate angiogenesis by stimulating Smad 1/5/8 signaling prompted by PML downregulation in endothelial cells .…”

Section: Introductionmentioning

confidence: 99%

Lack of miR‐1246 in small extracellular vesicle blunts tumorigenesis of laryngeal carcinoma cells by regulating Cyclin G2

et al. 2020

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Small extracellular vesicle (sEV) has precise impacts on tumor microenvironment and play vital functions in intercellular interaction. However, the functional role of sEV miRNA on laryngeal squamous cell carcinoma (LSCC) is largely unresolved. Here, the expression of miR‐1246 in LSCC tissues and plasma sEV was examined. The internalization ability of sEV was determined by uptake assay. Then, the source and purity of sEV were checked through RNase and/or pharmacological inhibitors application. The invasion, migration, proliferation, and cell cycle assays were used to determine the altered abilities of miR‐1246 in sEV in LSCC. Finally, target gene of miR‐1246, Cyclin G2 (CCNG2), was stained immunohistochemically. In addition, the relationship between CCNG2 and clinicopathological features of patients was analyzed. We found that miR‐1246 was higher in LSCC tissues and plasma sEV. MiR‐1246 was enriched in sEV rather than soluble form. SEV could be internalized into adjacent cells. Lack of miR‐1246 in sEV abrogated the tumorigenesis of LSCC. Furthermore, CCNG2 knockdown arrested the cell cycle and correlated to clinicopathological features and prognosis of LSCC patients. Taken together, we found that the function of sEV miR‐1246 by regulating CCNG2 is responsible for LSCC advancement with emphasis on the main source of miR‐1246 mainly root in sEV rather than in soluble form.

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Exosomal microRNA miR-1246 induces cell motility and invasion through the regulation of DENND2D in oral squamous cell carcinoma

Cited by 163 publications

References 41 publications

Changes in the Expression of Circulating microRNAs in Systemic Lupus Erythematosus Patient Blood Plasma After Passing Through a Plasma Adsorption Membrane

Changes in the Expression of Circulating microRNAs in Systemic Lupus Erythematosus Patient Blood Plasma After Passing Through a Plasma Adsorption Membrane

Exosomal MicroRNA MiR-1246 Promotes Cell Proliferation, Invasion and Drug Resistance by Targeting CCNG2 in Breast Cancer

Lack of miR‐1246 in small extracellular vesicle blunts tumorigenesis of laryngeal carcinoma cells by regulating Cyclin G2

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