Role of regulatory miRNAs of the PI3K/AKT signaling pathway in the pathogenesis of breast cancer

Rahmani, Farzad; Ferns, Gordon A.; Talebian, Sahar; Nourbakhsh, Mahnaz; Avan, Amir

doi:10.1016/j.gene.2020.144459

Cited by 45 publications

(29 citation statements)

References 47 publications

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“…In particular, the alteration of the PI3K/AKT pathway is recognized as a hallmark of BC. Recent studies have highlighted how the modulation of some regulatory proteins in the PI3K/AKT pathway is mediated by various miRNAs [82,83]. In the same manner, several studies have demonstrated that the dysregulation of CCND1 is associated with cancer progression while the over-expression of EGFR and EGFR-ligands as well as the dysregulation of the RAS/RAF/ERK signaling pathway are associated with the acquisition of drug resistance associated with cancer progression [84][85][86].…”

Section: Discussionmentioning

confidence: 99%

Identification of Modulated MicroRNAs Associated with Breast Cancer, Diet, and Physical Activity

Falzone

Grimaldi

Celentano

et al. 2020

Cancers

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Background: Several studies have shown that healthy lifestyles prevent the risk of breast cancer (BC) and are associated with better prognosis. It was hypothesized that lifestyle strategies induce microRNA (miRNA) modulation that, in turn, may lead to important epigenetic modifications. The identification of miRNAs associated with BC, diet, and physical activity may give further insights into the role played by lifestyle interventions and their efficacy for BC patients. To predict which miRNAs may be modulated by diet and physical activity in BC patients, the analyses of different miRNA expression datasets were performed. Methods: The GEO DataSets database was used to select miRNA expression datasets related to BC patients, dietary interventions, and physical exercise. Further bioinformatic approaches were used to establish the value of selected miRNAs in BC development and prognosis. Results: The analysis of datasets allowed the selection of modulated miRNAs associated with BC development, diet, and physical exercise. Seven miRNAs were also associated with the overall survival of BC patients. Conclusions: The identified miRNAs may play a role in the development of BC and may have a prognostic value in patients treated with integrative interventions including diet and physical activity. Validation of such modulated miRNAs on BC patients undergoing lifestyle strategies will be mandatory.

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Section: Discussionmentioning

confidence: 99%

Identification of Modulated MicroRNAs Associated with Breast Cancer, Diet, and Physical Activity

Falzone

Grimaldi

Celentano

et al. 2020

Cancers

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“…The phosphatidylinositide-3-kinase (PI3K)/Akt signaling pathway regulates many biological processes including cancer cell growth and metastasis [ 18 , 19 ]. Consequently, aberrant activation of the PI3K/Akt signaling pathway is frequently associated with progressive BC, which could be resistant to anticancer therapies [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Tamoxifen and the PI3K Inhibitor: LY294002 Synergistically Induce Apoptosis and Cell Cycle Arrest in Breast Cancer MCF-7 Cells

et al. 2020

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Breast cancer is considered as one of the most aggressive types of cancer. Acquired therapeutic resistance is the major cause of chemotherapy failure in breast cancer patients. To overcome this resistance and to improve the efficacy of treatment, drug combination is employed as a promising approach for this purpose. The synergistic cytotoxic, apoptosis inducing, and cell cycle effects of the combination of LY294002 (LY), a phosphatidylinositide-3-kinase (PI3K) inhibitor, with the traditional cytotoxic anti-estrogen drug tamoxifen (TAM) in breast cancer cells (MCF-7) were investigated. LY and TAM exhibited potent cytotoxic effect on MCF-7 cells with IC50 values 0.87 µM and 1.02 µM. The combination of non-toxic concentration of LY and TAM showed highly significant synergistic interaction as observed from isobologram (IC50: 0.17 µM, combination index: 0.18, colony formation: 9.01%) compared to untreated control. The percentage of early/late apoptosis significantly increased after treatment of MCF-7 cells with LY and TAM combination: 40.3%/28.3% (p < 0.001), compared to LY single treatment (19.8%/11.4%) and TAM single treatment (32.4%/5.9%). In addition, LY and TAM combination induced the apoptotic genes Caspase-3, Caspase-7, and p53, as well as p21 as cell cycle promotor, and significantly downregulated the anti-apoptotic genes Bcl-2 and survivin. The cell cycle assay revealed that the combination induced apoptosis by increasing the pre-G1: 28.3% compared to 1.6% of control. pAKT and Cyclin D1 protein expressions were significantly more downregulated by the combination treatment compared to the single drug treatment. The results suggested that the synergistic cytotoxic effect of LY and TAM is achieved by the induction of apoptosis and cell cycle arrest through cyclin D1, pAKT, caspases, and Bcl-2 signaling pathways.

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“…The m-TOR complex is activated by AKT and regulates several cell growth functions, including protein synthesis, cell survival, and autophagy inhibition. Recent data show that PI3K signaling is frequently activated in several malignancies in humans, including breast cancer and prolonged activation of PI3K signaling is associated with poor prognosis and resistance to chemotherapy (21) .…”

Section: Role Of Pi3k Pathway On Apoptosismentioning

confidence: 99%

The Effect of Brown Seaweed (Sargassum sp.) Extract on Apoptosis Process in Breast Cancer – A Literature Review

Ismylatifa Devi,

Diah Purwaningsari,

Nita Pranitasari

et al. 2021

Indian Journal of Forensic Medicine & Toxicology

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Breast cancer was one of the most common types of cancer in women and the major cause of death. Chemotherapy in breast cancer caused toxicity to the normal cells, resistance to the drugs, and several other side effects. Seaweed had many functional compounds that could be used as adjuvant therapy in breast cancer because of its anti-cancer properties called the proapoptotic agent. These compounds were fucoidan, phloroglucinol, and fucoxanthin. Their proapoptotic mechanisms shown by the journal were through increasing proapoptotic protein expression, decreasing antiapoptotic protein expression, inducing oxidative stress production on the cancer cell, and inhibiting the PI3K pathway. This review concludes that the brown seaweed (Sargassum sp.), which contains fucoidan, phloroglucinol, and fucoxanthin, could increase breast cancer cells' apoptotic process.

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Role of regulatory miRNAs of the PI3K/AKT signaling pathway in the pathogenesis of breast cancer

Cited by 45 publications

References 47 publications

Identification of Modulated MicroRNAs Associated with Breast Cancer, Diet, and Physical Activity

Identification of Modulated MicroRNAs Associated with Breast Cancer, Diet, and Physical Activity

Tamoxifen and the PI3K Inhibitor: LY294002 Synergistically Induce Apoptosis and Cell Cycle Arrest in Breast Cancer MCF-7 Cells

The Effect of Brown Seaweed (Sargassum sp.) Extract on Apoptosis Process in Breast Cancer – A Literature Review

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