Expression, regulation and mechanism of action of the miR-17-92 cluster in tumor cells (Review)

Fang, Li-Li; Wang, Xinghui; Sun, Baofei; Zhang, Xiaodong; Zhu, Xuhui; Zhou, Yu; Luo, Heng

doi:10.3892/ijmm.2017.3164

Cited by 74 publications

(86 citation statements)

References 65 publications

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“…These polycistronic miRNA clusters are highly expressed in a wide range of tumor cells and cancers, such as lung, breast, pancreas, prostate, and thyroid cancer, as well as lymphomas 34 . Therefore, the majority of the previous studies aimed at studying their oncogenic ability to promote tumor cell proliferation, invasion, and metastases, and much fewer studies delineated antitumor properties of these clusters 35 …”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐93 targets WASF3 and functions as a metastasis suppressor in breast cancer

2020

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Cancer cells with cancer stem cell (CSC) properties initiate both primary tumor formation and metastases at distant sites. Acquisition of CSC properties is highly associated with epigenetic alterations, including those mediated by microRNAs (miRNAs). We have previously established the breast cancer patient‐derived tumor xenograft (PDX) mouse model in which CSC marker CD44+ cancer cells formed spontaneous microscopic metastases in the liver. In this PDX mouse, we found that the expression levels of 3 miRNAs (miR‐25, miR‐93, and miR‐106b) in the miR‐106b‐25 cluster were much lower in the CD44+ human cancer cells metastasized to the liver than those at the primary site. Constitutive overexpression of miR‐93 suppressed invasive ability and 3D‐organoid formation capacity of breast cancer cells in vitro and significantly suppressed their metastatic ability to the liver in vivo. Wiskott‐Aldrich syndrome protein family member 3 (WASF3), a regulator of both cytoskeleton remodeling and CSC properties, was identified as a functional target of miR‐93: overexpression of miR‐93 reduced the protein level of WASF3 in breast cancer cells and WASF3 rescued the miR‐93‐mediated suppression of breast cancer cell invasion. These findings suggest that miR‐93 functions as a metastasis suppressor by suppressing both invasion ability and CSC properties in breast cancers.

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Section: Discussionmentioning

confidence: 99%

MicroRNA‐93 targets WASF3 and functions as a metastasis suppressor in breast cancer

2020

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“…MiR-19b belongs to the miR-17-92 cluster, which is a typical highly conserved polycistronic miRNA cluster located on human chromosome 13 open reading frame 25. (34) Although its role in the regulation of tumor growth has been well characterized, (35)(36)(37) it was unclear whether it played a direct role in bone formation. Therefore, we sought to investigate its involvement in osteogenesis.…”

Section: Discussionmentioning

confidence: 99%

Circulating MicroRNA-19b Identified From Osteoporotic Vertebral Compression Fracture Patients Increases Bone Formation

Sun

Wang

et al. 2019

Journal of Bone and Mineral Research

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Circulating microRNAs (miRNAs) play important roles in regulating gene expression and have been reported to be involved in various metabolic diseases, including osteoporosis. Although the transcriptional regulation of osteoblast differentiation has been well characterized, the role of circulating miRNAs in this process is poorly understood. Here we discovered that the level of circulating miR-19b was significantly lower in osteoporotic patients with vertebral compression fractures than that of healthy controls. The expression level of miR-19b was increased during osteoblastic differentiation of human mesenchymal stem cells (hMSCs) and MC3T3-E1 cells, and transfection with synthetic miR-19b could promote osteoblastic differentiation of hMSCs and MC3T3-E1 cells. PTEN (phosphatase and tensin homolog deleted from chromosome 10) was found to be directly repressed by miR-19b, with a concomitant increase in Runx2 expression and increased phosphorylation of AKT (protein kinase B, PKB). The expression level of circulating miR-19b in aged ovariectomized mice was significantly lower than in young mice. Moreover, the osteoporotic bone phenotype in aged ovariectomized mice was alleviated by the injection of chemically modified miR-19b (agomiR-19b). Taken together, our results show that circulating miR-19b plays an important role in enhancing osteoblastogenesis, possibly through regulation of the PTEN/pAKT/Runx2 pathway, and may be a useful therapeutic target in bone loss disorders, such as osteoporosis.

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“…Therefore, it is important to identify whether | 1541 expressed in various tumor cells and types of cancer. [44][45][46][47] Previous studies have revealed that miR-19a triggers the EMT 48 and regulates the activity of CSCs. 46 Therefore, we proposed that PLGF promotes EMT and stemness through the c-MYC/miR-19a axis.…”

Section: Discussionmentioning

confidence: 99%

The PLGF/c‐MYC/miR‐19a axis promotes metastasis and stemness in gallbladder cancer

Jin

et al. 2018

Cancer Science

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Gallbladder cancer (GBC) is the most common malignant tumor of the biliary tract system. Epithelial–mesenchymal transition (EMT) plays a vital role in the process of tumor metastasis. Mesenchymal‐like cells can serve as a source of cancer stem cells, which can confer the EMT phenotype. Placental growth factor (PLGF) belongs to the vascular endothelial growth factor family and plays a vital role in cancer. However, the underlying molecular mechanisms about the influence of PLGF on EMT in GBC remain unknown. Here we show that PLGF expression levels were higher in GBC tissues than in normal adjacent tissues and were associated with poor prognosis in GBC patients. Exogenous PLGF enhanced the migration, invasion, and tumorsphere formation of GBC cells. Conversely, knockdown of PLGF decreased the aggressive phenotype of GBC cells. Mechanistically, exogenous PLGF upregulated microRNA‐19a (miR‐19a) expression through the activation of c‐MYC. Moreover, Spearman's correlation analysis showed a positive pairwise correlation among PLGF, c‐MYC, and miR‐19a expression in GBC tissues. Taken together, these results suggest that PLGF promotes EMT and tumorsphere formation through inducing miR‐19a expression by upregulating c‐MYC. Thus, PLGF could be a promising molecular therapeutic target for GBC.

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Expression, regulation and mechanism of action of the miR-17-92 cluster in tumor cells (Review)

Cited by 74 publications

References 65 publications

MicroRNA‐93 targets WASF3 and functions as a metastasis suppressor in breast cancer

MicroRNA‐93 targets WASF3 and functions as a metastasis suppressor in breast cancer

Circulating MicroRNA-19b Identified From Osteoporotic Vertebral Compression Fracture Patients Increases Bone Formation

The PLGF/c‐MYC/miR‐19a axis promotes metastasis and stemness in gallbladder cancer

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