miRNA-203 Modulates Aldosterone Levels and Cell Proliferation by Targeting Wnt5a in Aldosterone-Producing Adenomas

Peng, Kang-Yung; Chang, Hao‐Yu; Lin, Yu‐Feng; Chan, Chieh‐Kai; Chang, Chia‐Hui; Chueh, Shih-Chieh; Yang, Shaoyu; Huang, Kuo‐How; Lin, Yen‐Hung; Wu, Vin‐Cent; Wu, Kwan‐Dun

doi:10.1210/jc.2018-00746

Cited by 28 publications

(29 citation statements)

References 48 publications

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“…CNO-treated mice were sis (54). Within the ZG, most cells are positive for both β-catenin and Cyp11b2 (52), and it has been suggested that Wnt/β-catenin signaling can control aldosterone production (57,61). Activating mutations in CTNNB1, the gene that encodes β-catenin, have also been described in a small subset of human aldosterone-producing adenomas (62)(63)(64)(65).…”

Section: Methodsmentioning

confidence: 99%

Chemogenetic activation of adrenocortical Gq signaling causes hyperaldosteronism and disrupts functional zonation

Taylor¹,

Ullenbruch²,

Frucci³

et al. 2019

Journal of Clinical Investigation

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recombinase inserted into the Cyp11b2 locus (1). Mice were bred to be heterozygous for AS-Cre (AS +/Cre hM3Dq), which allowed them to maintain Cyp11b2 expression (1). The presence and localization of hM3Dq were confirmed by HA tag immunofluorescence (IF) staining. Adrenal Cyp11b2 expression arises after birth, therefore, low levels of adrenal hM3Dq were present in these mice early in life, at 3 weeks of age (Supplemental Figure 2; supplemental material available online with this article;

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Section: Methodsmentioning

confidence: 99%

Chemogenetic activation of adrenocortical Gq signaling causes hyperaldosteronism and disrupts functional zonation

Taylor¹,

Ullenbruch²,

Frucci³

et al. 2019

Journal of Clinical Investigation

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“…Consistent with previous reports, our study also found that Wnt5a level was significantly increased in glioma cell lines and tissues. Up-regulation of Wnt5a can induce Wnt/β-catenin activation (Peng et al 2018;Bo et al 2013). The mechanism by which Wnt signaling pathway regulating tumorigenesis involves many aspects such as signal transduction, cell cycle, cell proliferation migration and apoptosis (He et al 2019).…”

Section: Discussionmentioning

confidence: 99%

circKIF4A promotes tumorogenesis of glioma by targeting miR-139-3p to activate Wnt5a signaling

Huo

Wang

Bai

et al. 2020

Mol Med

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Background: Glioma has the characteristics of high incidence and mortality, and is a common malignant tumor of the central nervous system. Circular RNAs (circRNAs) have been reported to play vital roles in progression of cancer including glioma, and circKIF4A is up-regulated in glioma tissues. However, its role and mechanisms in gliomas are unclear.Methods: circKIF4A and miR-139-3p were determined by qRT-PCR. Transwell assay, wound-healing assay, cell colony formation and flow cytometry were performed to measure cell invasion, migration, proliferation and apoptosis. Western blotting was used to evaluate Wnt/β-catenin pathway-related protein. Luciferase reporter assays confirmed the relationship among circKIF4A, miR-139-3p and Wnt5a. Sphere formation was performed to measure the ability of glioma-initiating cells (GICs) spheroid formation. A nude mouse xenograft model was established and immunohistochemical staining was used to detect Ki-67 and Wnt5a levels.Results: circKIF4A and Wnt5a were up-regulated and miR-139-3p was down-regulated in both glioma cells and tissues. circKIF4A promoted Wnt5a expression by sponging miR-139-3p. Knockdown of circKIF4A inhibited the colony formation ability, migration and invasion, and promoted the apoptosis of glioma cells by regulating miR-139-3p. Knockdown of circKIF4A inhibited Wnt/β-catenin signaling pathway and proliferation-related signal via miR-139-3p. Furthermore, knockdown of circKIF4A or overexpression of miR-139 suppressed the ability of sphere formation of GICs and inhibitd Wnt/β-catenin signaling pathway and proliferation-related signal in GICs. Additionally, depletion of circKIF4A decreased the expression level of Wnt5a and Ki-67, inhibited tumorigenesis in xenograft modes.Conclusion: circKIF4A was overexpressed in glioma, and knockdown of circKIF4A suppressed glioma progression via miR-139-3p/Wnt5a axis. The results indicated that circKIF4A may be a potential target for clinical treatment of glioma.

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“…In another study, miRNA-mediated activation of the Wnt/β-catenin pathway was shown in the pathogenesis of APAs [62]. It is well known, that the Wnt/β-catenin pathway is involved in the regulation of cell proliferation and steroid biosynthesis in human adrenocortical cells [63][64][65][66].…”

Section: Reviewmentioning

confidence: 99%

“…With a high-throughput miRNA-microarray method Peng et al have found two Wnt/β-catenin pathway-related miRNAs, hsa-miR-375 and hsa-miR-203 as the most significantly underexpressed miRNAs in APAs relative to adjacent normal adrenal tissues [62]. Moreover, expression of hsa-miR-203 has been negatively correlated with the plasma aldosterone level in APA patients [62]. In breast cancer cells, the epigenetical silencing of hsa-miR-203 via hypomethylation has led to the activation of the Wnt/β-catenin pathway [67].…”

Section: Reviewmentioning

confidence: 99%

MicroRNAs and Adrenocortical Tumors: Where do we Stand on Primary Aldosteronism?

et al. 2020

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MicroRNAs, the endogenous mediators of RNA interference, interact with the renin-angiotensin-aldosterone system, regulate aldosterone secretion and aldosterone effects. Some novel data show that the expression of some microRNAs is altered in primary aldosteronism, and some of these appear to have pathogenic relevance, as well. Differences in the circulating microRNA expression profiles between the two major forms of primary aldosteronism, unilateral aldosterone-producing adenoma and bilateral adrenal hyperplasia have also been shown. Here, we present a brief synopsis of these findings focusing on the potential relevance of microRNA in primary aldosteronism.

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miRNA-203 Modulates Aldosterone Levels and Cell Proliferation by Targeting Wnt5a in Aldosterone-Producing Adenomas

Abstract: We have demonstrated that attenuated miR-203 expression in APAs increases aldosterone production and the tumorigenesis of adrenal cells by activating the Wnt5a/β-catenin pathway.

Cited by 28 publications

References 48 publications

Chemogenetic activation of adrenocortical Gq signaling causes hyperaldosteronism and disrupts functional zonation

Chemogenetic activation of adrenocortical Gq signaling causes hyperaldosteronism and disrupts functional zonation

circKIF4A promotes tumorogenesis of glioma by targeting miR-139-3p to activate Wnt5a signaling

MicroRNAs and Adrenocortical Tumors: Where do we Stand on Primary Aldosteronism?

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