MiR-31 promotes mammary stem cell expansion and breast tumorigenesis by suppressing Wnt signaling antagonists

Lv, Cong; Li, Fengyin; Li, Xiang; Tian, Ye; Zhang, Yue; Sheng, Xiaole; Song, Yongli; Meng, Qingyong; Yuan, Shukai; Luan, Liming; Andl, Thomas; Feng, Xu; Jiao, Baowei; Xu, Mingang; Plikus, Maksim V.; Dai, Xing; Lengner, Christopher J.; Cui, Wei; Ren, Fazheng; Shuai, Jianwei; Millar, Sarah E.; Yu, Zhengquan

doi:10.1038/s41467-017-01059-5

Cited by 150 publications

(116 citation statements)

References 71 publications

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“…Thus, miR‐600 inhibits CSC renewal, resulting in suppression of tumor‐seeding ability. By contrast, miR‐31 promotes the tumor‐seeding ability of breast cancer cells through activating WNT signaling …”

Section: Tumorigenicitymentioning

confidence: 99%

Development of miRNA‐based therapeutic approaches for cancer patients

Takahashi

Prieto‐Vila

Kohama³

et al. 2019

Cancer Science

102

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Over the past few decades, si RNA and mi RNA have attracted a great deal of attention from researchers and clinicians. These molecules have been extensively studied from the standpoint of developing biopharmaceuticals against various diseases, including heart disease, diabetes and cancers. si RNA suppresses only a single target, whereas each mi RNA regulates the expression of multiple target genes. More importantly, because mi RNA are also secreted from cancer cells, and their aberrant expression is associated with tumor development and progression, they represent not only therapeutic targets but also promising biomarkers for diagnosis and prognosis. Therefore, mi RNA may be more effective tools against cancers, in which multiple signal pathways are dysregulated. In this review, we summarize recent progress in the development of mi RNA therapeutics for the treatment of cancer patients, and describe delivery systems for oligonucleotide therapeutics.

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Section: Tumorigenicitymentioning

confidence: 99%

Development of miRNA‐based therapeutic approaches for cancer patients

Takahashi

Prieto‐Vila

Kohama³

et al. 2019

Cancer Science

102

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“…Our previous results also demonstrated that SATB2 improves the stemness capacity and osteogenic differentiation of aged human BMSCs (Zhou et al., 2016). In addition, miR‐31a‐5p has been reported to directly target bone relevant markers, such as RUNX2, OSX, and DKK1 (Baglio, Devescovi, Granchi, & Baldini, 2013; Deng, Wu et al., 2013; Gao et al., 2011; Lv et al., 2017). Furthermore, it has been reported that regulation of miR‐31a‐5p expression could be used to modulate senescence‐related pathological conditions such as cancer, and the aging process (Capri et al., 2017; Cho, Dimri, & Dimri, 2015), which highlights us the important role of miR‐31a‐5p in cellular senescence.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment

et al. 2018

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The alteration of age‐related molecules in the bone marrow microenvironment is one of the driving forces in osteoporosis. These molecules inhibit bone formation and promote bone resorption by regulating osteoblastic and osteoclastic activity, contributing to age‐related bone loss. Here, we observed that the level of microRNA‐31a‐5p (miR‐31a‐5p) was significantly increased in bone marrow stromal cells (BMSCs) from aged rats, and these BMSCs demonstrated increased adipogenesis and aging phenotypes as well as decreased osteogenesis and stemness. We used the gain‐of‐function and knockdown approach to delineate the roles of miR‐31a‐5p in osteogenic differentiation by assessing the decrease of special AT‐rich sequence‐binding protein 2 (SATB2) levels and the aging of BMSCs by regulating the decline of E2F2 and recruiting senescence‐associated heterochromatin foci (SAHF). Notably, expression of miR‐31a‐5p, which promotes osteoclastogenesis and bone resorption, was markedly higher in BMSCs‐derived exosomes from aged rats compared to those from young rats, and suppression of exosomal miR‐31a‐5p inhibited the differentiation and function of osteoclasts, as shown by elevated RhoA activity. Moreover, using antagomiR‐31a‐5p, we observed that, in the bone marrow microenvironment, inhibition of miR‐31a‐5p prevented bone loss and decreased the osteoclastic activity of aged rats. Collectively, our results reveal that miR‐31a‐5p acts as a key modulator in the age‐related bone marrow microenvironment by influencing osteoblastic and osteoclastic differentiation and that it may be a potential therapeutic target for age‐related osteoporosis.

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“…Functionly, miRNAs were paid high attention in diverse pathophysiological processes including the initiation and progression of human maliganancies (Hannafon & Ding, ). Accumulating evidence suggests that a wide range of dysregulated miRNAs could act as oncogenic and tumor‐suppressive genes (Liu et al, ; Liu et al, ; Lv et al, ; Si et al, ). Human miR‐142‐3p situates at chromosome 17q22, which was regarded as a BC susceptibility locus with risky polymorphisms by genome‐wide association studies (Ahmed et al, ; Turnbull et al, ).…”

Section: Introductionmentioning

confidence: 99%

MiR‐142‐3p functions as a tumor suppressor by targeting RAC1/PAK1 pathway in breast cancer

Pan

et al. 2019

Journal Cellular Physiology

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MicroRNA -142-3p (miR-142-3p) was previously investigated in various cancers, whereas, itʼs role in breast cancer (BC) remains far from understood. In this study, we found that miR-142-3p was markedly decreased both in cell lines and BC tumor tissues. Elevated miR-142-3p expression suppressed growth and metastasis of BC cell lines via gain-of-function assay in vitro and in vivo. Mechanistically, miR-142-3p could regulate the ras-related C3 botulinum toxin substrate 1 (RAC1) expression in protein level, which simultaneously suppressed the epithelial-to-mesenchymal transition related protein levels and the activity of PAK1 phosphorylation, respectively. In addition, rescue experiments revealed RAC1 overexpression could reverse tumorsuppressive role of miR-142-3p. Our results showed miR-142-3p could function as a tumor suppressor via targeting RAC1/PAK1 pathway in BC, suggesting a potent therapeutic target for BC treatment. K E Y W O R D Sbreast cancer, miR-142-3p, PAK1, RAC1

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MiR-31 promotes mammary stem cell expansion and breast tumorigenesis by suppressing Wnt signaling antagonists

Cited by 150 publications

References 71 publications

Development of miRNA‐based therapeutic approaches for cancer patients

Development of miRNA‐based therapeutic approaches for cancer patients

MicroRNA‐31a‐5p from aging BMSCs links bone formation and resorption in the aged bone marrow microenvironment

MiR‐142‐3p functions as a tumor suppressor by targeting RAC1/PAK1 pathway in breast cancer

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