EZH2-Mediated microRNA-375 Upregulation Promotes Progression of Breast Cancer via the Inhibition of FOXO1 and the p53 Signaling Pathway

Guan, Xin; Shi, Aiping; Zou, Yabin; Sun, Meiyang; Zhan, Yue; Dong, Yi; Fan, Zhimin

doi:10.3389/fgene.2021.633756

Cited by 26 publications

(18 citation statements)

References 38 publications

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“…Also, the authors showed that this miRNA was associated with pathways related to proteoglycans in cancer and focal adhesion 116 . In a different study, the overexpression or miR‐375 through the activation of STAT3 by enhancer of zeste homologue 2 (EZH2) leads the downregulation forkhead box protein O1 and p53, an important antitumor proteins 117 . Interestingly, in a mouse model, Chiba et al 118 observed significantly increased serum levels of miR‐375‐3p after the exposition to radiation.…”

Section: Discussionmentioning

confidence: 99%

“…116 In a different study, the overexpression or miR-375 through the activation of STAT3 by enhancer of zeste homologue 2 (EZH2) leads the downregulation forkhead box protein O1 and p53, an important antitumor proteins. 117 Interestingly, in a mouse model, Chiba et al 118 observed significantly increased serum levels of miR-375-3p after the exposition to radiation. Moreover, miR-375 desensitizes gastric cancer cells to radiation by targeting p53.…”

Section: Discussionmentioning

confidence: 99%

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The cell cycle‐related genes RHAMM, AURKA, TPX2, PLK1, and PLK4 are associated with the poor prognosis of breast cancer patients

Kahl

Mense

Finke

et al. 2022

J of Cellular Biochemistry

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Breast cancer is the third most common type of cancer diagnosed. Cell cycle is a complex but highly organized and controlled process, in which normal cells sense mitogenic growth signals that instruct them to enter and progress through their cell cycle. This process culminates in cell division generating two daughter cells with identical amounts of genetic material. Uncontrolled proliferation is one of the hallmarks of cancer. In this study, we analyzed the expression of the cell cycle-related genes receptor for hyaluronan (HA)mediated motility (RHAMM), AURKA, TPX2, PLK1, and PLK4 and correlated them with the prognosis in a collective of 3952 breast cancer patients. A high messenger RNA expression of all studied genes correlated with a poor prognosis. Stratifying the patients according to the expression of hormonal receptors, we found that in patients with estrogen and progesterone receptorpositive and human epithelial growth factor receptor 2-negative tumors, and Luminal A and Luminal B tumors, the expression of the five analyzed genes correlates with worse survival. qPCR analysis of a panel of breast cancer cell lines representative of major molecular subtypes indicated a predominant expression in the luminal subtype. In vitro experiments showed that radiation influences the expression of the five analyzed genes both in luminal and triplenegative model cell lines. Functional analysis of MDA-MB-231 cells showed that small interfering RNA knockdown of PLK4 and TPX2 and pharmacological inhibition of PLK1 had an impact on the cell cycle and colony formation.Looking for a potential upstream regulation by microRNAs, we observed a differential expression of RHAMM, AURKA, TPX2, PLK1, and PLK4 after transfecting the MDA-MB-231 cells with three different microRNAs. Survival

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The cell cycle‐related genes RHAMM, AURKA, TPX2, PLK1, and PLK4 are associated with the poor prognosis of breast cancer patients

Kahl

Mense

Finke

et al. 2022

J of Cellular Biochemistry

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“…Experimental studies have shown that curcumin can inhibit EZH2 (enhancer of zest homolog-2), which is a histone methyltransferase that catalyzes the trimethylation of histone H3 in lys 27 (H3K27me3), is found in an increased amount in human cancer, has an oncogenic, metastatic role, and influences drug resistance. It was postulated that, on the EZH2, miR-375, FOXO1 and p53 axis, special processes with direct impact in the proliferation of the breast tumor could take place [86,87]. Gallardo et al showed, in a study on MCF-10F and MDA-MB-231 cell lines of human breast cancer, that curcumin can modulate the expression of miR-34a and Rho-A, which reduces cancer progression, metastasis, and increases the sensitivity of anti-cancer drugs [88].…”

Section: Breast Cancermentioning

confidence: 99%

Latest Innovations and Nanotechnologies with Curcumin as a Nature-Inspired Photosensitizer Applied in the Photodynamic Therapy of Cancer

Ailioaie

Litscher

2021

Pharmaceutics

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In the context of the high incidence of cancer worldwide, state-of-the-art photodynamic therapy (PDT) has entered as a usual protocol of attempting to eradicate cancer as a minimally invasive procedure, along with pharmacological resources and radiation therapy. The photosensitizer (PS) excited at certain wavelengths of the applied light source, in the presence of oxygen releases several free radicals and various oxidation products with high cytotoxic potential, which will lead to cell death in irradiated cancerous tissues. Current research focuses on the potential of natural products as a superior generation of photosensitizers, which through the latest nanotechnologies target tumors better, are less toxic to neighboring tissues, but at the same time, have improved light absorption for the more aggressive and widespread forms of cancer. Curcumin incorporated into nanotechnologies has a higher intracellular absorption, a higher targeting rate, increased toxicity to tumor cells, accelerates the activity of caspases and DNA cleavage, decreases the mitochondrial activity of cancer cells, decreases their viability and proliferation, decreases angiogenesis, and finally induces apoptosis. It reduces the size of the primary tumor, reverses multidrug resistance in chemotherapy and decreases resistance to radiation therapy in neoplasms. Current research has shown that the use of PDT and nanoformulations of curcumin has a modulating effect on ROS generation, so light or laser irradiation will lead to excessive ROS growth, while nanocurcumin will reduce the activation of ROS-producing enzymes or will determine the quick removal of ROS, seemingly opposite but synergistic phenomena by inducing neoplasm apoptosis, but at the same time, accelerating the repair of nearby tissue. The latest curcumin nanoformulations have a huge potential to optimize PDT, to overcome major side effects, resistance to chemotherapy, relapses and metastases. All the studies reviewed and presented revealed great potential for the applicability of nanoformulations of curcumin and PDT in cancer therapy.

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“…In recent times, miR-375 has been proved as a tumor-induced regulator in different cancers by activating important regulatory networks. For example, Xin et al demonstrated that overexpression of the miR-375 mediates phosphorylation and methylation of STAT3; also inhibits FOXO1 and p53 axis thereby stimulating the breast cancer progression (15) . Overexpression of circ-0072088 or miR-375 inhibitors promoted hepatocellular carcinoma proliferation, migration, invasion and reduced the cell death by activating JAK2/STAT3 network whereas circ-0072088 downregulation or miR-375 mimics explored opposite function (16) and also miR-375 activated JAK2/STAT3 signaling pathway to inhibit stemness of the breast cancer (17) .…”

Section: Introductionmentioning

confidence: 99%

“…Alam et al found that MiR-375 regulates cell growth, proliferation, cell migration, and apoptosis by modulating the CTGF-EGFR-PIK3CA-AKT signaling axis in human colorectal cancer cells (18) . Furthermore, several investigations were demonstrated that constitutive expression of miR-375 promotes oncogenicity in the breast (19)(20)(21)(22)(23) , prostate (24)(25)(26)(27) , and lung cancer (28) . In addition, few pieces of literature reported that miR-375 functions as a tumor suppressor (16,(29)(30)(31) .…”

Section: Introductionmentioning

confidence: 99%

Knockdown of microRNA-375 suppresses cell proliferation and promotes apoptosis in human breast cancer cells

Moorthy¹,

Srinivasan²,

Jayamohan³

et al. 2021

IJST

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Background:The purpose of the present investigation is to unravel the influence of the miR-375 inhibitor on cell survival descent and apoptosis stimulation, mediating PI3K/Akt/mTOR signaling network in human breast cancer cells. Methods: MCF-7 cells were transfected with miR-375 inhibitor for 72 h. Then, cell survival assay was measured by MTT. Cells were stained with EtBr/AO, DAPI, and DCFH-DA to assess the effect of the miR-375 inhibitor on cell death. A scratch experiment was performed to observe the cell migration ability. The expression of anti-apoptotic and apoptotic genes such as BCL-2, BAX, and PI3K/Akt/mTOR and miR-375 were evaluated in miR-375 inhibitor transfected cells by qRT-PCR. Findings: MiR-375 inhibitor sensitized tumor cells and influenced significant loss in the breast cancer cell proliferation with obvious cell death elevation. MiR-375 inhibitor effectively augmented ROS generation. Also, miR-375 inhibition hampered migratory ability. Furthermore, our qRT-PCR analysis showed that inhibition of the miR-375 was able to significantly reduce the constitutive expression of PI3K/Akt/mTOR mRNAs. Additionally, miR-375 suppression decreased the anti-apoptotic gene, Bcl-2 expression and enhanced pro-apoptotic gene, Bax expression along with potentially decreasing miR-375 level compared to control. Novelty and applications: Inhibition of the miR-375 has considerably attenuated cell proliferation and stimulated apoptotic cell death in the breast cancer cells. Thus, miR-375 represent a potential therapeutic target for the breast cancer.

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EZH2-Mediated microRNA-375 Upregulation Promotes Progression of Breast Cancer via the Inhibition of FOXO1 and the p53 Signaling Pathway

Cited by 26 publications

References 38 publications

The cell cycle‐related genes RHAMM, AURKA, TPX2, PLK1, and PLK4 are associated with the poor prognosis of breast cancer patients

The cell cycle‐related genes RHAMM, AURKA, TPX2, PLK1, and PLK4 are associated with the poor prognosis of breast cancer patients

Latest Innovations and Nanotechnologies with Curcumin as a Nature-Inspired Photosensitizer Applied in the Photodynamic Therapy of Cancer

Knockdown of microRNA-375 suppresses cell proliferation and promotes apoptosis in human breast cancer cells

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