Modulation of telomerase expression and function by miRNAs: Anti-cancer potential

Salamati, Aysan; Majidinia, Maryam; Asemi, Zatollah; Sadeghpour, Alireza; Oskoii, Meisagh Asanjani; Shanebandi, Dariush; Alemi, Forough; Mohammadi, Erfan; Karimian, Ansar; Targhazeh, Niloufar; Hoseini, Foroogh; Shirzad, Moein; Farsad-Akhtar, Nader; Safa, Amin; Yousefi, Bahman

doi:10.1016/j.lfs.2020.118387

Cited by 14 publications

(4 citation statements)

References 91 publications

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“…MiRNAs have been confirmed to participate in post-transcriptional gene expression regulation, acting as oncogenes or tumor suppressors [ 30 , 31 ]. In addition, the evidence demonstrated that tumor cells exhibit increased intrinsic ROS stress due to increased metabolic activity and mitochondrial malfunction [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Acidic Tumor Microenvironment Promotes Pancreatic Cancer through miR-451a/MEF2D Axis

Yao

et al. 2022

Journal of Oncology

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Pancreatic cancer (PC), as a highly malignant and aggressive solid tumor, is common in the digestive system. The acidic microenvironment is one of the critical markers of cancer. Nonetheless, there are few studies on how the acidic microenvironment affects the development of PC. This study focused on investigating the specific molecular mechanisms of the acidic microenvironment in PC. In our study, qRT-PCR was conducted for examining microRNA (miR)-451a and myocyte enhancer factor 2D (MEF2D) expressions in PANC-1 cells. Then, detailed functional effects of an acidic environment on miR-451a and MEF2D in PANC-1 cells were detected by CCK-8, colony formation, flow cytometry, wound healing, transwell, mitochondrial functionality measurement, JC-1 staining, DCFH-DA staining, and sphere formation assays. The relationship between miR-451a and MEF2D was confirmed by luciferase reporter analysis. Under acidic conditions, the increase of proliferation, migration, and invasion of PANC-1 cells was observed. Moreover, the mitochondrial oxidative respiration-related gene miR-451a was reduced in acidic conditions. In addition, we found that, in PANC-1 cells under an acidic environment, miR-451a overexpression enhanced oxygen consumption, mitochondrial membrane potential (MMP) loss, and ROS generation and inhibited proliferation, migration, invasion, and stemness via sponging MEF2D. In a word, our results revealed that the acidic microenvironment regulated PC progression by affecting the miR-451a/MEF2D axis, indicating a novel avenue for the future treatment of PC.

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Section: Discussionmentioning

confidence: 99%

Acidic Tumor Microenvironment Promotes Pancreatic Cancer through miR-451a/MEF2D Axis

Yao

et al. 2022

Journal of Oncology

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“…A growing body of evidence has demonstrated that miRNAs are important intracellular regulatory molecules that are becoming the focus of studies on various diseases, especially in the regulation of immune responses (41)(42)(43)(44). MiRNAs are differentially expressed in the cellular senescence and play important role in regulating of genes expression involved in features of ageing (45)(46)(47). Data from several studies suggest that the expression of miR-21 in the brain and heart of aged mice was significantly increased compared with adult mice (48,49).…”

Section: Discussionmentioning

confidence: 99%

hPMSCs-Derived Exosomal miRNA-21 Protects Against Aging-Related Oxidative Damage of CD4+ T Cells by Targeting the PTEN/PI3K-Nrf2 Axis

et al. 2021

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Mesenchymal stem cells (MSCs)-derived exosomes were considered a novel therapeutic approach in many aging-related diseases. This study aimed to clarify the protective effects of human placenta MSCs-derived exosomes (hPMSC-Exo) in aging-related CD4+ T cell senescence and identified the underlying mechanisms using a D-gal induced mouse aging model. Senescent T cells were detected SA-β-gal stain. The degree of DNA damage was evaluated by detecting the level of 8-OH-dG. The superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activities were measured. The expression of aging-related proteins and senescence-associated secretory phenotype (SASP) were detected by Western blot and RT-PCR. We found that hPMSC-Exo treatment markedly decreased oxidative stress damage (ROS and 8-OH-dG), SA-β-gal positive cell number, aging-related protein expression (p53 and γ-H2AX), and SASP expression (IL-6 and OPN) in senescent CD4+ T cells. Additionally, hPMSC-Exo containing miR-21 effectively downregulated the expression of PTEN, increased p-PI3K and p-AKT expression, and Nrf2 nuclear translocation and the expression of downstream target genes (NQO1 and HO-1) in senescent CD4+ T cells. Furthermore, in vitro studies uncovered that hPMSC-Exo attenuated CD4+ T cell senescence by improving the PTEN/PI3K-Nrf2 axis by using the PTEN inhibitor bpV (HOpic). We also validated that PTEN was a target of miR-21 by using a luciferase reporter assay. Collectively, the obtained results suggested that hPMSC-Exo attenuates CD4+ T cells senescence via carrying miRNA-21 and activating PTEN/PI3K-Nrf2 axis mediated exogenous antioxidant defenses.

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“…It appears that Aurora-B can attenuate apoptosis and enhance drug resistance in cancer cells by attenuating the p53-dependent DNA damage response [164]. ATRX plays a variety of roles in the cell, including maintaining the structural integrity of the telomere, replicating DNA, and repairing DNA [165][166][167]. A study of glioma cells showed that knocking out the ATRX gene using the CRISPR/Cas9 system could significantly enhance the apoptotic effects of TMZ.…”

Section: Application Of Crispr/cas9 System In Identification Of Drug-...mentioning

confidence: 99%

CRISPR/Cas9 gene editing: a new approach for overcoming drug resistance in cancer

et al. 2022

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The CRISPR/Cas9 system is an RNA-based adaptive immune system in bacteria and archaea. Various studies have shown that it is possible to target a wide range of human genes and treat some human diseases, including cancers, by the CRISPR/Cas9 system. In fact, CRISPR/Cas9 gene editing is one of the most efficient genome manipulation techniques. Studies have shown that CRISPR/Cas9 technology, in addition to having the potential to be used as a new therapeutic approach in the treatment of cancers, can also be used to enhance the effectiveness of existing treatments. Undoubtedly, the issue of drug resistance is one of the main obstacles in the treatment of cancers. Cancer cells resist anticancer drugs by a variety of mechanisms, such as enhancing anticancer drugs efflux, enhancing DNA repair, enhancing stemness, and attenuating apoptosis. Mutations in some proteins of different cellular signaling pathways are associated with these events and drug resistance. Recent studies have shown that the CRISPR/Cas9 technique can be used to target important genes involved in these mechanisms, thereby increasing the effectiveness of anticancer drugs. In this review article, studies related to the applications of this technique in overcoming drug resistance in cancer cells will be reviewed. In addition, we will give a brief overview of the limitations of the CRISP/Cas9 gene-editing technique.

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Modulation of telomerase expression and function by miRNAs: Anti-cancer potential

Cited by 14 publications

References 91 publications

Acidic Tumor Microenvironment Promotes Pancreatic Cancer through miR-451a/MEF2D Axis

Acidic Tumor Microenvironment Promotes Pancreatic Cancer through miR-451a/MEF2D Axis

hPMSCs-Derived Exosomal miRNA-21 Protects Against Aging-Related Oxidative Damage of CD4+ T Cells by Targeting the PTEN/PI3K-Nrf2 Axis

CRISPR/Cas9 gene editing: a new approach for overcoming drug resistance in cancer

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