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

ABSTRACT: 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??B 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??B 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??B p65(Rel) signaling pathway, suggesting that miR?188?5p may be a promising future target for BC treatment.

SUBMITTER: Yang Z

PROVIDER: S-EPMC7448417 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Yang Zhiguang Z Liu Zhaoyu Z Chang Zhihui Z Yan Guangxin G

Oncology reports 20200812 4

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 sev ...[more]

PMID: 32945499

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Project description:Studies performed in the last two decades have identified microRNA (miR)-1298-5p to display tumor-suppressive functions in several types of malignancy. In addition, the regulatory role of E2F transcription factor 1 (E2F1) has been reported in multiple types of cancer, including breast cancer (BC). However, whether miR-1298-5p participates in BC progression and whether a regulatory association exists between miR-1298-5p and E2F1 remains to be explored. The present study aimed to determine the role of miR-1298-5p and its interaction with E2F1 in BC. The expression of miR-1298-5p and E2F1 was examined by reverse transcription-quantitative PCR and western blot assays. The viability and proliferative capacity of BC cells were evaluated by Cell Counting Kit-8 and 5-bromo-2'-deoxyuridine assays, respectively. The apoptotic rate was assessed by the caspase-3 activity assay and flow cytometry; the protein expression levels of vimentin and E-cadherin were evaluated by western blotting. In addition, the adhesive and migratory abilities of BC cells were determined by conducting cell adhesion and wound healing assay, respectively. The target relationship between miR-1298-5p and E2F1 was validated by the luciferase reporter assay. The results of the present study revealed that the levels of miR-1298-5p were downregulated in BC tissues and cells compared with those in normal breast tissues and cells, respectively. In addition, miR-1298-5p was demonstrated to inhibit the proliferation, adhesion and migration of BC cells and to promote BC cell apoptosis. E2F1 was verified as a target gene of miR-1298-5p using the luciferase reporter assay. Additionally, E2F1 exhibited an opposite expression pattern compared with that of miR-1298-5p in BC tissues. Furthermore, the downregulation of miR-1298-5p in BC cells was reversed by silencing E2F1. Overall, the results of the present study suggested that miR-1298-5p repressed BC cell proliferation, adhesion and migration, and enhanced BC cell apoptosis by downregulating E2F1.

Project description:BackgroundAcute myeloid leukemia (AML) is a malignant clonal disease of hematopoietic stem- and progenitor-cell origin. AML features massive proliferation of abnormal blasts and leukemia cells in the bone marrow and the inhibition of normal hematopoiesis at onset. Exosomes containing proteins or nucleic acids are secreted by cells; they participate in intercellular communication and serve as key modulators of hematopoiesis. The purpose of this study was to investigate the effects of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) on the regulation of AML and the underlying mechanisms mediated by microRNA (miRNA).MethodsDysregulated miR-7-5p in AML patients was identified using qRT-PCR and its clinical significance was explored. Bioinformatic analysis revealed the target gene OSBPL11 that could be regulated by miR-7-5p. The findings were validated using a dual-luciferase reporter assay and western blotting. The functional genes of the PI3K/AKT/mTOR signaling pathway were identified, and the functional significance of miR-7-5p in AML cells was determined using a functional recovery assay. AML cells were co-cultured with exosomes originating from BMSCs overexpressing miR-7-5p to determine cell-cell regulation by Exo-miR-7-5p, as well as in vitro and in vivo functional validation via gain- and loss-of-function methods.ResultsExpression of miR-7-5p was decreased in AML patients and cells. Overexpression of miR-7-5p curbed cellular proliferation and promoted apoptosis. Overexpression of OSBPL11 reversed the tumorigenic properties of miR-7-5p in AML cells in vitro. Exo-miR-7-5p derived from BMSCs induced formation of AML cells prone to apoptosis and a low survival rate, with OSBPL11 expression inhibited through the PI3K/AKT/mTOR signaling pathway. Exo-miR-7-5p derived from BMSCs exhibited tumor homing effects in vitro and in vivo, and inhibited AML development.ConclusionsExo-miR-7-5p derived from BMSCs negatively regulates OSBPL11 by suppressing the phosphorylation of the PI3K/AKT/mTOR signaling pathway, thereby inhibiting AML proliferation and promoting apoptosis. The data will inform the development of AML therapies based on BMSC-derived exosomes.

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

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

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