Complexity in the regulation of Dicer expression: Dicer variant proteins are differentially expressed in epithelial and mesenchymal breast cancer cells and decreased during EMT

Hinkal, George; Grelier, Gaël; Puisieux, Alain; Moyret‐Lalle, Caroline

doi:10.1038/sj.bjc.6606022

Cited by 18 publications

(26 citation statements)

References 5 publications

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“…Because of its role in microRNA processing from pre-miRs to mature microRNAs, DICER1 regulates cellular processes including cell differentiation, programmed cell death, senescence, DNA repair, and chromatin remodeling [52-56]. DICER1 expression was reported to be downregulated in breast cancer cells exhibiting mesenchymal phenotypes and in primary breast tumors of patients with lower disease free survival [57]. However, a larger study of primary breast tumors reported that DICER1 staining was associated with ER negativity, HER2+, high Ki67, and expression of basal-like biomarkers [58].…”

Section: Discussionmentioning

confidence: 99%

Tamoxifen differentially regulates miR-29b-1 and miR-29a expression depending on endocrine-sensitivity in breast cancer cells

et al. 2017

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Endocrine-resistance develops in ~ 40% of breast cancer patients after tamoxifen (TAM) therapy. Although microRNAs are dysregulated in breast cancer, their contribution to endocrine-resistance is not yet understood. Previous microarray analysis identified miR-29a and miR-29b-1 as repressed by TAM in MCF-7 endocrine-sensitive breast cancer cells but stimulated by TAM in LY2 endocrine-resistant breast cancer cells. Here we examined the mechanism for the differential regulation of these miRs by TAM in MCF-7 versus TAM-resistant LY2 and LCC9 breast cancer cells and the functional role of these microRNAs in these cells. Knockdown studies revealed that ERα is responsible for TAM regulation of miR-29b-1/a transcription. We also demonstrated that transient overexpression of miR-29b-1/a decreased MCF-7, LCC9, and LY2 proliferation and inhibited LY2 cell migration and colony formation but did not sensitize LCC9 or LY2 cells to TAM. Furthermore, TAM reduced DICER1 mRNA and protein in LY2 cells, a known target of miR-29. Supporting this observation, anti-miR-29b-1 or anti-miR-29a inhibited the suppression of DICER by 4-OHT. These results suggest miR-29b-1/a has tumor suppressor activity in TAM-resistant cells and does not appear to play a role in mediating TAM resistance.

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Section: Discussionmentioning

confidence: 99%

Tamoxifen differentially regulates miR-29b-1 and miR-29a expression depending on endocrine-sensitivity in breast cancer cells

et al. 2017

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“…In addition, numerous shorter alternative splicing products have been found. Some of these products encode proteins that retain only the functional RNase III domains of Dicer, and some variants do not encode any protein [19], [20].…”

Section: Introductionmentioning

confidence: 99%

“…The 3′-UTR is also involved in the regulation of Dicer gene expression. This region can be targeted by several miRNAs, for instance, miR-103/107 [20], [21] or let-7 miRNA [22]. Interestingly, target sequences for let-7 were also found in the coding region of Dicer mRNA [22].…”

Section: Introductionmentioning

confidence: 99%

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A New Short Oligonucleotide-Based Strategy for the Precursor-Specific Regulation of microRNA Processing by Dicer

et al. 2013

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The precise regulation of microRNA (miRNA) biogenesis seems to be critically important for the proper functioning of all eukaryotic organisms. Even small changes in the levels of specific miRNAs can initiate pathological processes, including carcinogenesis. Accordingly, there is a great need to develop effective methods for the regulation of miRNA biogenesis and activity. In this study, we focused on the final step of miRNA biogenesis; i.e., miRNA processing by Dicer. To test our hypothesis that RNA molecules can function not only as Dicer substrates but also as Dicer regulators, we previously identified by SELEX a pool of RNA oligomers that bind to human Dicer. We found that certain of these RNA oligomers could selectively inhibit the formation of specific miRNAs. Here, we show that these specific inhibitors can simultaneously bind both Dicer and pre-miRNAs. These bifunctional riboregulators interfere with miRNA maturation by affecting pre-miRNA structure and sequestering Dicer. Based on these observations, we designed a set of short oligomers (12 nucleotides long) that were capable of influencing pre-miRNA processing in vitro, both in reactions involving recombinant human Dicer and in cytosolic extracts. We propose that the same strategy may be used to develop effective and selective regulators to control the production of any miRNA. Overall, our findings indicate that the interactions between pre-miRNAs and other RNAs may form very complex regulatory networks that modulate miRNA biogenesis and consequently gene expression.

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“…Several studies suggested that estrogen induced changes in DICER expression may have global effects on miRNA levels by altering their processing rate [48–50]. In another study, decreased AGO1 and AGO2 expressions were detected in ER-positive tumors suggesting that the lower abundance of these argonaute proteins may limit the functional activity of the RNA Induced Silencing Complex (RISC) [51].…”

Section: Micrornas and Estrogen Receptor Signalingmentioning

confidence: 99%

miRNA clusters as therapeutic targets for hormone-resistant breast cancer

Leva

Cheung

Croce

2015

Expert Review of Endocrinology & Metabolism

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MicroRNAs are small non coding RNAs that typically inhibit the translation and stability of messenger RNAs, controlling genes involved in cellular processes such as inflammation, cell cycle regulation, stress response, differentiation, apoptosis, and migration. Not surprisingly, microRNAs are also aberrantly expressed in cancer and promote tumorigenesis by disrupting these vital cellular functions. In this review, we first broadly summarize the role of microRNAs in breast cancer and Estrogen Receptor alpha signaling. Then we focus on what is currently known about the role of microRNAs in anti-hormonal therapy or resistance to endocrine agents. Specifically, we will discuss key miRNAs involved in tamoxifen (miR-221/222, 181, 101, 519a, 301, 375, 342, 451, and the let-7 family), fulvestrant (miR-221/222, miR-200 family), and aromatase inhibitor (miR-128 and the let-7 family) resistance.

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Complexity in the regulation of Dicer expression: Dicer variant proteins are differentially expressed in epithelial and mesenchymal breast cancer cells and decreased during EMT

Cited by 18 publications

References 5 publications

Tamoxifen differentially regulates miR-29b-1 and miR-29a expression depending on endocrine-sensitivity in breast cancer cells

Tamoxifen differentially regulates miR-29b-1 and miR-29a expression depending on endocrine-sensitivity in breast cancer cells

A New Short Oligonucleotide-Based Strategy for the Precursor-Specific Regulation of microRNA Processing by Dicer

miRNA clusters as therapeutic targets for hormone-resistant breast cancer

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