MiR-591 functions as tumor suppressor in breast cancer by targeting TCF4 and inhibits Hippo-YAP/TAZ signaling pathway

Huang, Xiaohong; Tang, Fuchou; Weng, Zeping; Zhou, Mengyao; Zhang, Qing

doi:10.1186/s12935-019-0818-x

Cited by 29 publications

(16 citation statements)

References 17 publications

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“…Previous evidence has shown that YAP1 exerts an oncogenic function in several types of human cancer, such as breast and lung cancer ( 22 , 23 ). As the findings of the present study revealed that YAP1 is upregulated in CC, it was hypothesized that YAP1 may act as an oncogenic gene in CC.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA‑15a‑5p‑targeting oncogene YAP1 inhibits cell viability and induces cell apoptosis in cervical cancer cells

et al. 2020

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MicroRNAs (miRNAs) have been reported to have important regulatory roles in the progression of several types of cancer, including cervical cancer (CC). However, the biological roles and regulatory mechanisms of miRNAs in CC remain to be fully elucidated. The aim of the present study was to examine the functions of miRNAs in CC and the possible mechanisms. Using a microarray, it was identified that miRNA-15a-5p (miR-15a-5p) was one of the most down-regulated miRNAs in CC tissues compared with adjacent noncancerous tissues. The low expression of miR-15a-5p was observed in CC tumor tissues with distant metastasis and in CC cell lines. In addition, the effects of miR-15a-5p upregulation on cell viability, apoptosis, invasion and migration of CC cells were investigated using CCK-8, flow cytometry, Transwell and wound healing assays, respectively. It was demonstrated that upregulation of miR-15a-5p significantly suppressed the viability, migration and invasion, and promoted the apoptosis of SiHa and C-33A cells. Furthermore, yes-associated protein 1 (YAP1), a well-known oncogene, was confirmed to be directly targeted by miR-15a-5p and was found to be negatively regulated by miR-15a-5p. Further correlation analysis indicated that miR-15a-5p expression was negatively correlated with YAP1 expression in CC tissues. Notably, overexpression of YAP1 abrogated the tumor suppressive effects of miR-15a-5p in CC cells. Taken together, these present findings indicated that the miR-15a-5p/YAP1 axis may provide a novel strategy for the clinical treatment of CC.

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Section: Resultsmentioning

confidence: 99%

MicroRNA‑15a‑5p‑targeting oncogene YAP1 inhibits cell viability and induces cell apoptosis in cervical cancer cells

et al. 2020

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“…A previous study demonstrated that miR-495 can inhibit the progression of non-small cell lung cancer by targeting TCF4 (39). Previous research has confirmed that the inhibitory effects of miR-591 expression on breast cancer cell proliferation and invasion are mediated by TCF4 (40). Crucially, it has been found that the overexpression of miR-299-3p can inhibit CC cell growth and invasion.…”

Section: Discussionmentioning

confidence: 82%

miR-326 inhibits the cell proliferation and cancer stem cell-like property of cervical cancer in vitro and oncogenesis in vivo via targeting TCF4

Zhang¹,

He²,

Wang³

et al. 2020

Ann Transl Med

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Background: Cervical cancer ranks as one of the most prevalent female malignancies globally, and its treatment with new targets has been the focus of current research. The present study set out to investigate the function of microRNA-326 (miR-326) in vitro and in vivo and to verify the direct targeting of transcription factor 4 (TCF4) by miR-326. Methods: The detection of messenger RNA (mRNA) expressing miR-326 and TCF4 in cervical cancer cell lines and tumor samples was conducted using quantitative real-time polymerase chain (qRT-PCR). A dualluciferase reporter assay was carried out to detect the target relationship of miR-326 with TCF4. A Cell Counting Kit-8 (CCK-8) assay was employed to detect the effect of miR-326 on CasKi cell viability. Flow cytometry and western blotting were employed to examine the effects of miR-326 on cancer stem cell (CSC)like property. Tumor weight was measured in orthotopic xenograft mouse models. Immunohistochemistry was employed to analyze the protein expression levels of Ki-67, proliferating cell nuclear antigen (PCNA), CD44, and SRY-box 4 (SOX4). Result: Downregulation of the mRNA expression levels of miR-326 was observed in cervical cancer cell lines and tumor tissue, while the levels of TCF4 were upregulated. The dual-luciferase reporter assay revealed binding of miR-326 to the three prime untranslated region (3'-UTR) of TCF4. In vitro assays demonstrated that miR-326 inhibited CasKi cell proliferation through regulating TCF4. miR-326 also suppressed the CSC-like property of CasKi cells by targeting TCF4. Furthermore, the protein expression levels of cyclin D1, β-catenin, and c-Myc were decreased when miR-326 was added to TCF4-transfected cells. In vivo assays demonstrated that miR-326 inhibited tumor weight, growth, and the protein expression levels of Ki-67, PCNA, CD44, SOX4, and β-catenin.Conclusions: miR-326 acted in a tumor-suppressive manner through its regulation of TCF4, and has potential as a biomarker or therapeutic target for cervical cancer.

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“…Luo et al revealed that miR-212 was significantly downregulated in human osteosarcoma tissues, and ectopic miR-212 expression suppressed the proliferation and invasion of osteosarcoma cells [31], and this was subsequently validated by studies by Liu et al [32] and Li et al [33]. The miR-591 gene was initially identified as a tumor-suppressor gene due to its downregulation in breast cancer tissues, and low miR-591 expression was found to be involved in lymph node metastasis and advanced TNM stage in patients with breast cancer [34]. Further, Niu et al [35] found that miR-153 was downregulated in osteosarcoma tissues compared with normal controls, potentially acting as a tumor suppressor through negatively regulating TGF-b2 expression, which agrees with the results of Wang et al [36].…”

Section: Discussionmentioning

confidence: 88%

Identification and Validation of a Potent Multi-miRNA Signature for Prediction of Prognosis of Osteosarcoma Patients

et al. 2020

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Departmental sources Background: Osteosarcoma, the most common solid malignancy, has high incidence and mortality rates. We constructed a miRNA-based signature that can be used to assess the prognosis of osteosarcoma patients. Material/Methods: The miRNA profile was derived from the Gene Expression Omnibus (GEO) website, with matched clinical records. The miRNA-based overall survival (OS)-predicting signature was established by LASSO Cox regression analysis. Receiver operating characteristic (ROC) curve and Kaplan-Meier (K-M) analyses were performed to examine the stability and discriminatory ability of the OS-predicting signatures. Pathway enrichment analyses were performed to uncover potential mechanisms. Results: Three miRNAs (miR-153, miR-212, and miR-591) independently related to the OS were extracted to build a risk score formula. The ROC curve and K-M analyses revealed good discrimination ability of the OS signature for osteosarcoma patients in both the training cohort (P=0.00015, AUC=0.962) and the validation cohort (P=0.0065, AUC=0.793). As shown in multivariate analysis, the classifier showed favorable predictive accuracy similar to the recurrence status to be an independent risk factor for osteosarcoma. Furthermore, the nomogram showed a synergistic effect by combining the clinicopathological features with our classifier. Also, the enrichment analyses of the target genes may contribute to improved treatment of osteosarcoma. Conclusions: The 3-miRNA-based classifier serves as an effective prognosis-predicting signature for osteosarcoma patients.

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MiR-591 functions as tumor suppressor in breast cancer by targeting TCF4 and inhibits Hippo-YAP/TAZ signaling pathway

Cited by 29 publications

References 17 publications

MicroRNA‑15a‑5p‑targeting oncogene YAP1 inhibits cell viability and induces cell apoptosis in cervical cancer cells

MicroRNA‑15a‑5p‑targeting oncogene YAP1 inhibits cell viability and induces cell apoptosis in cervical cancer cells

miR-326 inhibits the cell proliferation and cancer stem cell-like property of cervical cancer in vitro and oncogenesis in vivo via targeting TCF4

Identification and Validation of a Potent Multi-miRNA Signature for Prediction of Prognosis of Osteosarcoma Patients

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