Downregulation of miR‐375 in aldosterone‐producing adenomas promotes tumour cell growth via <scp>MTDH</scp>

He, Jinzhi; Cao, Yanan; Su, Tingwei; Jiang, Yiran; Jiang, Lei; Zhou, Weiwei; Zhang, Cui; Wang, Weiqing; Ning, Guang

doi:10.1111/cen.12814

Cited by 34 publications

(35 citation statements)

References 39 publications

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“…Aldosterone‐producing adrenocortical adenoma and normal adrenal gland tissue have been demonstrated by miRNA microarray analysis to have different miRNA expression profiles (He et al . ). Nevertheless, few miRNAs have been demonstrated to play a role in the pathogenesis of APA.…”

Section: Discussionmentioning

confidence: 97%

“…However, the expression of miR‐140‐3p, miR‐193a‐3p and miR‐22‐3p in 15 paired samples of APA and adjacent normal adrenal gland tissue measured by qRT‐PCR in this study is not in accordance with those in previous studies; He et al . () showed by miRNA microarray analysis that miR‐140‐3p, miR‐193a‐3p and miR‐22‐3p are all upregulated in nine APA tissue compared with that in four normal human adrenal cortex tissue. This difference may be a result of the difference in methods used for miRNA detection, the difference in patients’ sample number and the difference references used to compare miRNA expression.…”

Section: Discussionmentioning

confidence: 98%

“…In addition, He et al . () assessed miRNA expression in APA, unilateral adrenal hyperplasia (UAH) and normal adrenal cortex tissue by microarray profiling and found that 31 miRNAs, including miR‐140‐3p, miR‐193a‐3p and miR‐22‐3p, were differentially expressed significantly in these three groups. Interestingly, these three miRNAs have binding sites in the 3ʹ‐UTR of CYP11B2 (Lewis et al .…”

mentioning

confidence: 99%

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MiR‐193a‐3p functions as a tumour suppressor in human aldosterone‐producing adrenocortical adenoma by down‐regulating CYP11B2

Zhang

Zou

Liu

et al. 2018

Int J Experimental Path

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The mechanism of aldosterone-producing adrenocortical adenoma (APA) pathogenesis and the role of microRNAs (miRNAs) in APA pathogenesis have not been completely clarified. We examined the expression and function of miR-140-3p, miR-193a-3p and miR-22-3p, which have binding sites in CYP11B2. Expression of miRNAs and CYP11B2 mRNA was measured by quantitative reverse transcription PCR (qRT-PCR). Cell proliferation was monitored by colorimetric analysis, and cell apoptosis and cell cycle progression were analysed by flow cytometry. ELISA was carried out to detect aldosterone levels in cell culture supernatants. Luciferase reporter assays, qRT-PCR and Western blotting were performed to identify CYP11B2 as a target of miR-193a-3p. Of the three miRNAs examined, miR-193a-3p exhibited a significant decrease and CYP11B2 mRNA exhibited a significant increase in expression in APA compared with adjacent normal adrenal gland tissue. Transfection of miR-193a-3p mimic into the human adrenocortical cell line H295R showed that elevated miR-193a-3p expression inhibits proliferation and aldosterone secretion, induces G1-phase arrest and promotes apoptosis in H295R cells. Furthermore, in luciferase reporter assays, overexpression of miR-193a-3p in H295R cells significantly reduced the luciferase activity of the wild-type CYP11B2 3'-UTR construct, which could be reversed by mutation of the miR-193a-3p-binding site. Moreover, miR-193a-3p overexpression downregulated CYP11B2 mRNA and protein expression. Finally, overexpression of CYP11B2 diminished the effects of miR-193a-3p on H295R cells. Taken together, our results suggest that CYP11B2 levels may be modulated by miR-193a-3p in APA, which could explain, at least partially, why downregulation of miR-193a-3p during APA formation may promote cell growth and suppress apoptosis.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

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MiR‐193a‐3p functions as a tumour suppressor in human aldosterone‐producing adrenocortical adenoma by down‐regulating CYP11B2

Zhang

Zou

Liu

et al. 2018

Int J Experimental Path

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“…He et al studied the miRNA expression of APAs, unilateral adrenal hyperplasia (UAH) and normal adrenal cortex tissues with high-throughput methods [49]. By miRNA-microarray profiling, 31 miRNAs were found to be significantly differentially expressed in the three studied groups.…”

Section: Pathogenic Relevance Of Mirnas In the Molecular Pathomechanimentioning

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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“…Somatic mutations occurring in KCNJ5, CACNA1D, ATP1A1, ATP2B3, and CTNNB1 genes give rise to sporadic APA [61]. In addition to the abovementioned mutations, regulatory RNAs such as miRNAs have also been shown to be important in modulating aldosterone levels and tumorigenesis [62][63][64]. On the other hand, adrenocortical cancers (ACC), some of which are hormone-producing, occur relatively rarely, and patients with ACC exhibit poor prognosis with a median survival of 5.5 years [65].…”

Section: Adrenocortical Cancermentioning

confidence: 99%

Investigating the Role of Mineralocorticoid Receptor Signaling in Cancer Biology in the Genomic Era

Konu¹,

Targen²

2019

Aldosterone-Mineralocorticoid Receptor - Cell Biology to Translational Medicine

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In the last decades, advances that take place in the next-generation sequencing and bioinformatics research have helped reveal tissue-and cancer-specific gene expression patterns and mutation landscapes. Indeed, such data are now easily accessible via online genome browsers and different types and levels of public data compendia. Appropriate use of these tools eventually can lead to better patient stratification for diagnosis, prognosis, and therapy of cancers. Mineralocorticoid receptor (MR), encoded by NR3C2 gene, has long been implicated in the development and progression of multiple cancers. Nevertheless, MR has remained relatively understudied at the genomic and transcriptomic levels. In this review, we present the current, literature-based state of knowledge on the role of MR primarily in epithelial cancers. At the same time, we summarize the gene expression, mutation, and copy number variation data on MR obtained from The Cancer Genome Atlas (TCGA). We also show that MR expression could be a promising prognostic marker in different cancers using online tools for survival data analysis. Accordingly, this review strongly demonstrates the emerging potential of studying MR using available tools from the genomics/transcriptomics field for improving cancer diagnosis and prognostication.

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Downregulation of miR‐375 in aldosterone‐producing adenomas promotes tumour cell growth via MTDH

Abstract: Our findings suggest that miR-375 exerts its tumour-suppressive function via targeting MTDH/Akt pathway and implicate a potential therapeutic target in PA.

Cited by 34 publications

References 39 publications

MiR‐193a‐3p functions as a tumour suppressor in human aldosterone‐producing adrenocortical adenoma by down‐regulating CYP11B2

MiR‐193a‐3p functions as a tumour suppressor in human aldosterone‐producing adrenocortical adenoma by down‐regulating CYP11B2

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

Investigating the Role of Mineralocorticoid Receptor Signaling in Cancer Biology in the Genomic Era

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