2.4 GHz Electromagnetic Field Influences the Response of the Circadian Oscillator in the Colorectal Cancer Cell Line DLD1 to miR-34a-Mediated Regulation

Olejárová, Soňa; Moravčík, Roman; Herichová, Iveta

doi:10.3390/ijms232113210

Cited by 6 publications

(11 citation statements)

References 140 publications

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“…miR-34a administration also inhibited the expression of the clock gene bmal1 and the clock-controlled gene rev-erbα, which agrees with the search performed in miRWalk [66] and previous research [63]. Surprisingly, we observed an elevated level of the clock mRNA concentration after miR-34a administration.…”

Section: Plos Onesupporting

confidence: 92%

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Effect of miR-34a on the expression of clock and clock-controlled genes in DLD1 and Lovo human cancer cells with different backgrounds with respect to p53 functionality and 17β-estradiol-mediated regulation

Moravčík,

Olejárová,

Zlacká

et al. 2023

PLoS ONE

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The small non-coding RNA miR-34a is a p53-regulated miRNA that acts as a tumour suppressor of colorectal cancer (CRC). Oncogenesis is also negatively influenced by deregulation of the circadian system in many types of tumours with various genetic backgrounds. As the clock gene per2 was recently recognized as one of the target genes of miR-34a, we focused on the miR-34a-mediated influence on the circadian oscillator in CRC cell lines DLD1 and LoVo, which differ in their p53 status. Previously, a sex-dependent association between the expression of per2 and that of miR-34a was demonstrated in CRC patients. Therefore, we also investigated the effect of 17β-estradiol (E2) on miR-34a oncostatic functions. miR-34a mimic caused a pronounced inhibition of per2 expression in both cell lines. Moreover, miR-34a mimic significantly inhibited bmal1 expression in LoVo and rev-erbα expression in DLD1 cells and induced clock gene expression in both cell lines. miR-34a mimic caused a pronounced decrease in sirt1 and cyclin D1 expression, which may be related to the inhibition of proliferation observed after mir-34a administration in DLD1 cells. E2 administration inhibited the migration and proliferation of DLD1 cells. E2 and miR-34a, when administered simultaneously, did not potentiate each other’s effects. To conclude, miR-34a strongly influences the expression of components of the circadian oscillator without respect to p53 status and exerts its oncostatic effects via inhibition of sirt1 and cyclin D1 mRNA expression. E2 administration inhibits the growth of DLD1 cells; however, this effect seems to be independent of miR-34a-mediated action. With respect to the possible use of miR-34a in cancer treatment, clock genes can be considered as off-target genes, as changes in their expression induced by miR-34a treatment do not contribute to the oncostatic functions of miR-34a. Possible ambiguous oncogenic characteristics should be taken into consideration in future clinical studies focused on miR-34a.

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Section: Plos Onesupporting

confidence: 92%

“…administration of mimic miR-34a together with an inhibitor caused an increase in per2 expression. The same effect has been observed without regard to whether mature miR-34a or pre-miRNA was administered to the DLD1 cell culture [63].…”

Section: Plos Onesupporting

confidence: 67%

Effect of miR-34a on the expression of clock and clock-controlled genes in DLD1 and Lovo human cancer cells with different backgrounds with respect to p53 functionality and 17β-estradiol-mediated regulation

Moravčík,

Olejárová,

Zlacká

et al. 2023

PLoS ONE

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“…Studies that indicated miR-34a as a tumour suppressor have been criticised for the use of supra-physiological levels of synthetic mimics [48], and the off-target activity of miR-34a has been demonstrated recently [37]. We have also observed the effect of a high-frequency electromagnetic field (RF-EMF) on the oncostatic functions of miR-34a [36].…”

Section: Functions Of Small Non-coding Rnas and Their Modulation By E...mentioning

confidence: 78%

“…An altered functionality of miR-34a in the colorectal cancer cell line DLD1 exposed to EMF with 2.4 GHz frequency (RF-EMF) was demonstrated by our group [36]. The exposure of DLD1 cells to RF-EMF potentiates the capacity of miR-34a to induce the expression of the clock gene cry1 that was not observed under control conditions.…”

Section: Interference Of An Electromagnetic Field On Mir-34-mediated ...mentioning

confidence: 85%

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Impact of Long-Lasting Environmental Factors on Regulation Mediated by the miR-34 Family

Štefánik,

Morová,

Herichová

2024

Biomedicines

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The present review focuses on the interactions of newly emerging environmental factors with miRNA-mediated regulation. In particular, we draw attention to the effects of phthalates, electromagnetic fields (EMFs) and a disrupted light/dark cycle. miRNAs are small non-coding RNA molecules with a tremendous regulatory impact, which is usually executed via gene expression inhibition. To address the capacity of environmental factors to influence miRNA-mediated regulation, the miR-34 family was selected for its well-described oncostatic and neuro-modulatory properties. The expression of miR-34 is in a tissue-dependent manner to some extent under the control of the circadian system. There is experimental evidence implicating that phthalates, EMFs and the circadian system interact with the miR-34 family, in both lines of its physiological functioning. The inhibition of miR-34 expression in response to phthalates, EMFs and light contamination has been described in cancer tissue and cell lines and was associated with a decline in oncostatic miR-34a signalling (decrease in p21 expression) and a promotion of tumorigenesis (increases in Noth1, cyclin D1 and cry1 expressions). The effects of miR-34 on neural functions have also been influenced by phthalates, EMFs and a disrupted light/dark cycle. Environmental factors shifted the effects of miR-34 from beneficial to the promotion of neurodegeneration and decreased cognition. Moreover, the apoptogenic capacity of miR-34 induced via phthalate administration in the testes has been shown to negatively influence germ cell proliferation. To conclude, as the oncostatic and positive neuromodulatory functions of the miR-34 family can be strongly influenced by environmental factors, their interactions should be taken into consideration in translational medicine.

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miRNA-mediated regulation of clock gene expression in men and women with colorectal cancer and possible consequences for disease management

Herichová

2024

Biomedical Journal

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2.4 GHz Electromagnetic Field Influences the Response of the Circadian Oscillator in the Colorectal Cancer Cell Line DLD1 to miR-34a-Mediated Regulation

Cited by 6 publications

References 140 publications

Effect of miR-34a on the expression of clock and clock-controlled genes in DLD1 and Lovo human cancer cells with different backgrounds with respect to p53 functionality and 17β-estradiol-mediated regulation

Effect of miR-34a on the expression of clock and clock-controlled genes in DLD1 and Lovo human cancer cells with different backgrounds with respect to p53 functionality and 17β-estradiol-mediated regulation

Impact of Long-Lasting Environmental Factors on Regulation Mediated by the miR-34 Family

miRNA-mediated regulation of clock gene expression in men and women with colorectal cancer and possible consequences for disease management

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