miR‐188‐5p suppresses cellular proliferation and migration via IL6ST: A potential noninvasive diagnostic biomarker for breast cancer

Wang, Mei; Zhang, Huiling; Yang, Fang; Qiu, Rong; Zhao, Xinxin; Gong, Zheng; Yu, Wanjun; Zhou, Beixian; Shen, Bo; Zhu, Wei

doi:10.1002/jcp.29367

Cited by 37 publications

(28 citation statements)

References 44 publications

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“…MiR-373 was shown to enhance cell migration by suppressing ITGA2, the lack of which plays a relevant role in metastasis spread [85]; moreover, it was found hyper-expressed in TNBC [86]. Multiple roles were reported for miR-188, which negatively regulated cell proliferation and migration by targeting IL6ST [87] or enhanced apoptosis by suppressing the anti-apoptosis and pro-survival Rap2c [88].…”

Section: Discussionmentioning

confidence: 99%

Circulating MicroRNAs as Prognostic and Therapeutic Biomarkers in Breast Cancer Molecular Subtypes

Zelli

Compagnoni

Capelli

et al. 2020

JPM

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Breast cancer (BC) is a common and heterogeneous disease, of which six molecular subtypes, characterized by different biological features and clinical outcomes, were described. The identification of additional biomarkers able to further connote and distinguish the different BC subtypes is essential to improve the diagnostic, prognostic and therapeutic strategies in BC patients. MicroRNAs (miRNAs) are short non-coding RNA involved in several physiological and pathological processes, including cancer development and progression. In particular, circulating miRNAs, which can be found in an adequately stable structure in serum/plasma of cancer patients, are emerging as very promising non-invasive biomarkers. Several studies have analyzed the potential role of circulating miRNAs as prognostic and therapeutic markers in BC. In the present review we describe circulating miRNAs, identified as putative biomarker in BC, with special reference to different BC molecular subtypes.

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Section: Discussionmentioning

confidence: 99%

Circulating MicroRNAs as Prognostic and Therapeutic Biomarkers in Breast Cancer Molecular Subtypes

Zelli

Compagnoni

Capelli

et al. 2020

JPM

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“…It has been reported that miR-188-5p is involved in cell proliferation and tumor growth in a variety of cancers. 10,[14][15][16] The results of cell functional experiments showed that high expression of miR-188-5p promoted the viability, cell cycle progression, proliferation, and tumor growth, and inhibited apoptosis in APL cells. In contrast, the effect of miR-188-5p silencing on the proliferation, apoptosis, and tumor growth was opposite to that of the highly expressed miR-188-5p phenotype in APL cells.…”

Section: Discussionmentioning

confidence: 99%

“…32,33 It has been reported that miR-188-5p in Keloids inhibits cell proliferation and invasion via PI3K/ Akt/MMP-2/9 signaling 34 and in chronic myeloid leukemia-induced cell apoptosis by repressing the PI3K/AKT signaling. 16 The above results suggest that miR188-5p was involved in the activation of the PI3K/AKT/mTOR signaling pathway. CD2AP links actin to PI3K kinase activity to extend epithelial cell height and constrain cell area.…”

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confidence: 83%

“…14,15 MiR-188-5p, a suppressor gene, inhibits cell proliferation and metastasis in colon cancer and breast cancer. 16,17 However, miR188-5p was highly expressed in neutralizing cells of patients with chronic myeloid leukemia. 18 Overexpression of miRNA-188-5p significantly suppressed the proliferative ability and arrested cell cycle progression of osteosarcoma cells via targeting CCNT2.…”

Section: Introductionmentioning

confidence: 99%

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<p>miR-188-5p Promotes Tumor Growth by Targeting CD2AP Through PI3K/AKT/mTOR Signaling in Children with Acute Promyelocytic Leukemia</p>

Wang

Chen

Ding

et al. 2020

OTT

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Purpose: Pediatric acute promyelocytic leukemia (APL) accounts for 10% of pediatric acute myelogenous leukemia (AML) case and is accompanied by a tendency to hemorrhage. miR-188-5p plays an important role in adult AML. Therefore, the purpose of this study was to explore the effects of miR-188-5p on cell proliferation and apoptosis and tumor growth, and its mechanism in pediatric APL patients. Materials and Methods: Survival-associated miRNAs or mRNAs from TCGA database associated with AML were identified via using the "survival R" package in R language. CCK8, clone formation, flow cytometry, RT-PCR, immunohistochemistry and Western blot assays were used to detect the viability, proliferation, apoptosis, cell cycle, and related gene expression in APL cell lines. The prognostic value of miR-188-5p was evaluated using a ROC curve. The tumorigenic ability of APL cell lines was determined using a nude mouse transplantation tumor experiment. Tumor cell apoptosis was determined by TUNEL assay in vivo. The target genes of miR-188-5p were predicted using the miRDB, miRTarBase, and TargetScan databases. A PPI network was constructed using STRING database and the hub gene was identified using the MCODE plug-in of the Cytoscape software. The DAVID database was used to perform GO and KEGG pathway enrichment analyses. A luciferase reporter assay was used to demonstrate the binding of miR-188-5p to CD2AP. Results: miR-188-5p overexpression or CD2 associated protein (CD2AP) inhibition was significantly associated with poor survival in pediatric APL patients. Upregulation of miR-188-5p was identified in the blood of pediatric APL patients and cell lines. Increased expression of miR-188-5p also promoted the viability, proliferation, and cell cycle progression, and reduced the apoptosis of APL cells. Additionally, upregulation of miR-188-5p regulated the expressions of cyclinD1, p53, Bax, Bcl-2 and cleaved caspase-3. The area under the ROC curve (AUC) of miR-188-5p was 0.661. miR-188-5p overexpression increased the tumorigenic ability of APL and Ki67 expression, and reduced cell apoptosis in vivo. CD2AP was identified as the only overlapping gene from the list of miR-188-5p target genes and survival-related mRNAs of the TCGA database. It was mainly enriched in the "biological process (BP)" and "cellular component (CC)" terms, and was downregulated in the blood of pediatric APL patients and cell lines. The luciferase reporter, RT-PCR, and Western blot assays demonstrated that the binding of miR-188-5p to CD2AP. CD2AP inhibition promoted the proliferation and inhibited the apoptosis of APL cells. Rescue experiments showed that inhibition of miR-188-5p inhibited cell proliferation, activated the PI3K/AKT/mTOR signaling pathway, induced G0/G1 phase arrest, regulated gene expression, and promoted cell apoptosis, which were reversed by CD2AP inhibition.

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“…Wang et al reported that circulating miR-188-5p was upregulated in BC patients and associated with TNM of BC; interestingly, miR-188-5p was downregulated in BC MDA-MB-231 and MCF-7 cells. Moreover, using gain-of-and loss-of-function analyses of miR-188-5p in breast cancer cells the authors demonstrated that miR-188-5p inhibited the proliferation and invasion of BC MDA-MB-231 cells via targeting IL6ST (21). However, we demonstrated that the expression of miR-188-5p was drastically downregulated in BC tissue specimens, which was also decreased in BC cell lines, MDA-MB-231, BT549 and MCF-7, compared to normal breast epithelial cell line MCF-10A.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑188‑5p inhibits the progression of breast cancer by targeting zinc finger protein 91

et al. 2020

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Breast cancer (BC) is the most commonly diagnosed malignant cancer in women. BC is the main cause of cancer-related death in women and seriously threatens the life and health of women worldwide. MicroRNAs (miRNAs/miRs) have been reported to regulate the development and progression of different types of cancer. However, the regulatory functions of miR-188-5p in BC have not been thoroughly demonstrated. In this present research, we identified that miR-188-5p was downregulated in BC tissues and several BC cell lines. Downregulation of miR-188-5p was significantly associated with advanced TNM stage. Moreover, we identified that miR-188-5p mimics significantly inhibited proliferation using CCK-8 assay, colony formation and xenograft animal model, suppressed invasion and migration detected by Transwell invasion assay, and increased the cellular apoptosis of BC cells as determined by cell apoptosis assay. Moreover miR-188-5p mimics also reduced the expression of NF-κB p65(Rel). To further investigate its regulatory mechanism, transcription factor zinc finger protein 91 (ZFP91) was predicted as the targeted protein of miR-188-5p by bioinformatic method. We confirmed their specific binding by dual luciferase (DLR) assay. We demonstrated that the overexpression of miR-188-5p significantly inhibited the expression of ZFP91 in BC cell lines and reduced the expression of NF-κB p65(Rel). An inverse correlation was found between the expression of miR-188-5p and ZFP91 in BC tissues. Importantly, we demonstrated that the restoration of ZFP91 was able to block the effect of miR-188-5p on the progression of MDA-MB-231 cells. Therefore, our study showed that miR-188-5p may be one of the important indicators and could inhibit the progression of human BC via targeting the ZFP91/NF-κB p65(Rel) signaling pathway, suggesting that miR-188-5p may be a promising future target for BC treatment.

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miR‐188‐5p suppresses cellular proliferation and migration via IL6ST: A potential noninvasive diagnostic biomarker for breast cancer

Cited by 37 publications

References 44 publications

Circulating MicroRNAs as Prognostic and Therapeutic Biomarkers in Breast Cancer Molecular Subtypes

Circulating MicroRNAs as Prognostic and Therapeutic Biomarkers in Breast Cancer Molecular Subtypes

<p>miR-188-5p Promotes Tumor Growth by Targeting CD2AP Through PI3K/AKT/mTOR Signaling in Children with Acute Promyelocytic Leukemia</p>

MicroRNA‑188‑5p inhibits the progression of breast cancer by targeting zinc finger protein 91

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