GATA3-driven expression of miR-503 inhibits prostate cancer progression by repressing ZNF217 expression

Jiang, Xingkang; Chen, Yue; Du, Eugenie; Yang, Kuo; Zhang, Zhihong; Qi, Shiyong; Xu, Yong

doi:10.1016/j.cellsig.2016.06.002

Cited by 33 publications

(37 citation statements)

References 31 publications

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“…The luciferase activity and mRNA levels of miR-506-3p was significantly elevated in GATA3-transfected A549 cells, whereas silencing expression of GATA3 in HCC827 cells decreased the luciferase activity and mRNA expression of miR-506-3p (Figure 5C, P < 0.05; Supplementary Figure S3D–3E). A number of miRNAs were reported as direct targets of GATA3, such as miR-29b, miR-503 [27, 28]. As previous described, elevated GATA3 expression promotes miR-29b and miR-503 levels in A549 cells, while inhibition of GATA3 in HCC827 cells decreases miR-29b and miR-503 expression (Supplementary Figure S3D–3E).…”

Section: Resultsmentioning

confidence: 57%

“…In 2014, Chou and colleagues identified that GATA3 modulates miR-29b expression by binding to its core promoter [27]. In addition, Jiang et al and Wang et al demonstrated that GATA3 transcriptional actives the expression of miR-503 and miR-573 in prostate cancer [28, 29]. Nevertheless, we still have limited knowledge of aberrant expression and possible mechanisms of GATA3 in NSCLC patients.…”

Section: Discussionmentioning

confidence: 99%

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Genetic and epigenetic silencing of mircoRNA-506-3p enhances COTL1 oncogene expression to foster non-small lung cancer progression

et al. 2016

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Although previous studies suggested that microRNA-506-3p (miR-506-3p) was frequently downregulated, and functioned as a tumor suppressor in several cancers, the biological role and intrinsic regulatory mechanisms of miR-506-3p in non-small cell lung cancer (NSCLC) remain elusive. The present study found miR-506-3p expression was downregulated in advanced NSCLC tissues and cell lines. The expression of miR-506-3p in NSCLC was inversely correlated with larger tumor size, advanced TNM stage and lymph node metastasis. In addition, we also found patients with lower expression of miR-506-3p had a poor prognosis than those patients with higher expression of miR-506-3p. Function studies demonstrated that aberrant miR-506-3p expression modulates tumor cell growth, cell mobility, cell migration and invasion in vitro and in vivo. Mechanistic investigations manifested that coactosin-like protein 1 (COTL1) was a direct downstream target of miR-506-3p. Knockdown of COTL1 mimicked the tumor-suppressive effects of miR-506-3p overexpression in A549 cells, whereas COTL1 overexpression enhanced the tumorigenic function in HCC827 cells. Importantly, we also found GATA3 transcriptionally actives miR-506-3p expression, and the long non-coding RNA urothelial carcinoma-associated 1 (UCA1) exerts oncogenic function in NSCLC by competitively ‘sponging’ miRNA-506. Together, our combined results elucidated genetic and epigenetic silencing of miR-506-3p enhances COTL1 oncogene expression to foster NSCLC progression.

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Section: Resultsmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Genetic and epigenetic silencing of mircoRNA-506-3p enhances COTL1 oncogene expression to foster non-small lung cancer progression

et al. 2016

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“…Hyperplastic tissue remained epithelial in this system as evidenced by the maintenance of the epithelial markers E-cadherin, ZO-1, and Par complex components, suggesting that the role of Gata3 in prostate progenitor cells is different from the regulation of epithelial-mesenchymal transition reported in metastatic prostate cancer cells (Jiang et al., 2016, Wang et al., 2015). …”

Section: Discussionmentioning

confidence: 77%

Lineage Specification from Prostate Progenitor Cells Requires Gata3-Dependent Mitotic Spindle Orientation

et al. 2017

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SummaryDuring prostate development, basal and luminal cell lineages are generated through symmetric and asymmetric divisions of bipotent basal cells. However, the extent to which spindle orientation controls division symmetry or cell fate, and the upstream factors regulating this process, are still elusive. We report that GATA3 is expressed in both prostate basal progenitor and luminal cells and that loss of GATA3 leads to a mislocalization of PRKCZ, resulting in mitotic spindle randomization during progenitor cell division. Inherently proliferative intermediate progenitor cells accumulate, leading to an expansion of the luminal compartment. These defects ultimately result in a loss of tissue polarity and defective branching morphogenesis. We further show that disrupting the interaction between PRKCZ and PARD6B is sufficient to recapitulate the spindle and cell lineage phenotypes. Collectively, these results identify a critical role for GATA3 in prostate lineage specification, and further highlight the importance of regulating spindle orientation for hierarchical cell lineage organization.

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“…In support of this relationship, data from breast cancer patient cohorts show that high expression of ZNF217 is associated with worse survival (Gyorffy et al 2009;Frietze et al 2014), while high expression of miR-503 is associated with improved survival (Antonov 2011;Lyng et al 2012;Antonov et al 2013). Furthermore, while this manuscript was under review, another study was published demonstrating that the GATA3-driven expression of miR-503 represses ZNF217 in prostate cancer (Jiang et al 2016). Together, these observations point to the complexity of the estrogen-signaling network and further highlight the beneficial aspects of the estrogen response.…”

Section: Discussionmentioning

confidence: 73%

An integrative transcriptomics approach identifies miR-503 as a candidate master regulator of the estrogen response in MCF-7 breast cancer cells

Baran-Gale

Purvis

Sethupathy

2016

RNA

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Estrogen receptor α (ERα) is an important biomarker of breast cancer severity and a common therapeutic target. In response to estrogen, ERα stimulates a dynamic transcriptional program including both coding and noncoding RNAs. We generate a fine-scale map of expression dynamics by performing a temporal profiling of both messenger RNAs (mRNAs) and microRNAs (miRNAs) in MCF-7 cells (an ER+ model cell line for breast cancer) in response to estrogen stimulation. We identified three primary expression trends-transient, induced, and repressed-that were each enriched for genes with distinct cellular functions. Integrative analysis of mRNA and miRNA temporal expression profiles identified miR-503 as the strongest candidate master regulator of the estrogen response, in part through suppression of ZNF217-an oncogene that is frequently amplified in cancer. We confirmed experimentally that miR-503 directly targets ZNF217 and that overexpression of miR-503 suppresses MCF-7 cell proliferation. Moreover, the levels of ZNF217 and miR-503 are associated with opposite outcomes in breast cancer patient cohorts, with high expression of ZNF217 associated with poor survival and high expression of miR-503 associated with improved survival. Overall, these data indicate that miR-503 acts as a potent estrogen-induced candidate tumor suppressor miRNA that opposes cellular proliferation and has promise as a novel therapeutic for breast cancer. More generally, our work provides a systemslevel framework for identifying functional interactions that shape the temporal dynamics of gene expression.

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GATA3-driven expression of miR-503 inhibits prostate cancer progression by repressing ZNF217 expression

Cited by 33 publications

References 31 publications

Genetic and epigenetic silencing of mircoRNA-506-3p enhances COTL1 oncogene expression to foster non-small lung cancer progression

Genetic and epigenetic silencing of mircoRNA-506-3p enhances COTL1 oncogene expression to foster non-small lung cancer progression

Lineage Specification from Prostate Progenitor Cells Requires Gata3-Dependent Mitotic Spindle Orientation

An integrative transcriptomics approach identifies miR-503 as a candidate master regulator of the estrogen response in MCF-7 breast cancer cells

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