Identification of targets of tumor suppressor microRNA-34a using a reporter library system

Ito, Yoshiaki; Inoue, Atsushi; Seers, Timothy; Hato, Yukari; Igarashi, Arisa; Toyama, Tatsuya; Taganov, Konstantin D.; Boldin, Mark; Asahara, Hiroshi

doi:10.1073/pnas.1620019114

Cited by 44 publications

(32 citation statements)

References 67 publications

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“…MicroRNA-34a has attracted interest recently because of its ability to modulate a myriad of oncogenic functions in different cancers [21][22][23][24][25][26][27]. Not only does it play a role in cancer metastasis [28,29] and drug resistance [30], it is now being evaluated as a diagnostic as well as a prognostic biomarker [31][32][33].…”

Section: Introductionmentioning

confidence: 99%

miR-34a regulates adipogenesis in porcine intramuscular adipocytes by targeting ACSL4

Wang

Ding

et al. 2020

BMC Genet

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Background: Intramuscular fat (IMF) content is an important factor in porcine meat quality. Previously, we showed that miR-34a was less abundant in liver tissue from pigs with higher backfat thickness, compared to pigs with lower backfat thickness. The purpose of this present study was to explore the role of miR-34a in adipogenesis. Result: Bioinformatics analysis identified Acyl-CoA synthetase long chain family member 4 (ACSL4) as a putative target of miR-34a. Using a luciferase reporter assay, we verified that miR-34a binds the ACSL4 mRNA at the 3'UTR. To examine the role of the miR-34a-ACSL4 interaction in IMF deposition in the pig, mRNA and protein expression of the ACSL4 gene was measured in primary intramuscular preadipocytes transfected with miR-34a mimic and inhibitor. Our results showed that ACSL4 is expressed throughout the entire differentiation process in pig preadipocytes, similar to the lipogenesis-associated genes PPARγ and aP2. Transfection with miR-34a mimic reduced lipid droplet formation during adipogenesis, while miR-34a inhibitor increased lipid droplet accumulation. Transfection with miR-34a mimic also reduced the mRNA and protein expression of ACSL4 and lipogenesis genes, including PPARγ, aP2, and SREBP-1C, but increased the expression of steatolysis genes such as ATGL and Sirt1. In contrast, the miR-34a inhibitor had the opposite effect on gene expression. Further, knockdown of ACSL4 decreased lipid droplet accumulation. Conclusions: Our results support the hypothesis that miR-34a regulates intramuscular fat deposition in porcine adipocytes by targeting ACSL4.

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Section: Introductionmentioning

confidence: 99%

miR-34a regulates adipogenesis in porcine intramuscular adipocytes by targeting ACSL4

Wang

Ding

et al. 2020

BMC Genet

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“…Specifically, miRNA induce transcript degradation or inhibition of protein translation through sequence‐specific binding with the 3′UTR of their target mRNA (Figure ). miRNA also inhibit the translation or facilitate the cleavage of their target mRNA by binding to their CDS . To date, multiple miRNA have been identified in various types of cancers, and these tumor‐associated miRNA can be classified into two groups: TS‐miRNA and onco‐miRNA …”

Section: Introductionmentioning

confidence: 99%

Development of miRNA‐based therapeutic approaches for cancer patients

Takahashi

Prieto‐Vila

Kohama³

et al. 2019

Cancer Science

108

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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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“…In addition, this miRNA is a direct target of TP53 and together they form a positive feed-forward regulatory loop. All these characters make miR-34a a promising candidate for therapeutic interventions using methods to restore its expression levels (Slabáková et al, 2017;Ito et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Synergistic effect of microRNA and albumin-bound nanoparticles for inhibition of glioblastoma cancer cell proliferation

Shariatnasery

Irani

Soleimani

et al. 2020

Braz. J. Pharm. Sci.

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The functional significance of upregulation miR-34a in combination with albumin-bound paclitaxel nanoparticles in U251 glioblastoma cell line has been evaluated. The MTT assay determined that miR-34a and albumin-bound paclitaxel nanoparticles can reduce cell viability, but the combination of both factors has a stronger effect on cell viability. The application of qRT-PCR has demonstrated that the transduction of miR-34a could lead to exogenous upregulation of miR-34a level and downregulation of SURVIVIN. Moreover, treatment of U251 cells with miR-34a and nanoparticles together considerably inhibit SURVIVIN expression compared to miR-34a and nanoparticles alone. Flow cytometry showed that upon miR-34a overexpression cell cycle arrested in G1 phase, while treatment with nanoparticles increased the cell population in G2 phase. Upregulation of miR-34a along with treatment with nanoparticles elevated the number of cells arrested in G1/ G2 phases of the cell cycle. Expression of miR-34a with albumin-bound paclitaxel nanoparticles reduced cell viability, downregulated SURVIVIN and enhanced cell cycle arrest in G1/G2 phases. Thus, the upregulation of miR-34a with these nanoparticles are potential candidates therapeutic for glioblastoma cancer.

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Identification of targets of tumor suppressor microRNA-34a using a reporter library system

Cited by 44 publications

References 67 publications

miR-34a regulates adipogenesis in porcine intramuscular adipocytes by targeting ACSL4

miR-34a regulates adipogenesis in porcine intramuscular adipocytes by targeting ACSL4

Development of miRNA‐based therapeutic approaches for cancer patients

Synergistic effect of microRNA and albumin-bound nanoparticles for inhibition of glioblastoma cancer cell proliferation

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