MicroRNAs, Hypoxia and the Stem-Like State as Contributors to Cancer Aggressiveness

Macharia, Lucy Wanjiku; Muriithi, Wanjiru; Mureithi, Marianne; Pereira, Cláudia Maria; Ferrer, Valéria Pereira; Moura‐Neto, Vivaldo

doi:10.3389/fgene.2019.00125

Cited by 43 publications

(38 citation statements)

References 256 publications

(287 reference statements)

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“…In glioblastoma, miR-10b is upregulated in CSCs and its inhibition strongly reduces CSCs proliferation and metastasis. OncomiR-138 has also been identified as a prognostic biomarker of GSCs [180,182]. In ovarian cancer, miR-5703, miR-630, miR-1246 and miR-320b were significantly dysregulated in CSCs compared with primary cancer cells, whereas miR-424-5p level was lower and associated with distant metastasis [183].…”

Section: Secretome In Metastasismentioning

confidence: 99%

Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment

et al. 2020

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Cancer stem cells (CSCs) represent a tumor subpopulation responsible for tumor metastasis and resistance to chemo- and radiotherapy, ultimately leading to tumor relapse. As a consequence, the detection and eradication of this cell subpopulation represent a current challenge in oncology medicine. CSC phenotype is dependent on the tumor microenvironment (TME), which involves stem and differentiated tumor cells, as well as different cell types, such as mesenchymal stem cells, endothelial cells, fibroblasts and cells of the immune system, in addition to the extracellular matrix (ECM), different in composition to the ECM in healthy tissues. CSCs regulate multiple cancer hallmarks through the interaction with cells and ECM in their environment by secreting extracellular vesicles including exosomes, and soluble factors such as interleukins, cytokines, growth factors and other metabolites to the TME. Through these factors, CSCs generate and activate their own tumor niche by recruiting stromal cells and modulate angiogenesis, metastasis, resistance to antitumor treatments and their own maintenance by the secretion of different factors such as IL-6, VEGF and TGF-ß. Due to the strong influence of the CSC secretome on disease development, the new antitumor therapies focus on targeting these communication networks to eradicate the tumor and prevent metastasis, tumor relapse and drug resistance. This review summarizes for the first time the main components of the CSC secretome and how they mediate different tumor processes. Lastly, the relevance of the CSC secretome in the development of more precise and personalized antitumor therapies is discussed.

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Section: Secretome In Metastasismentioning

confidence: 99%

Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment

et al. 2020

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“…To identify candidate miRNAs of increased therapeutic importance, both upregulated and downregulated miRNAs in primary and metastatic brain cancers were compared. Based on the existing literature, differentially expressed miRNAs in GBM [117][118][119][120][121][122][123][124][125][126][127][128][129] and BrM [130][131][132][133][134][135][136][137] were grouped, which resulted in four different groups, including GBM upregulated, GBM downregulated, BrM upregulated, and BrM downregulated. Venn diagram-based comparison of miRNAs was then performed to identify the putative miRNAs of therapeutic importance ( Figure 2 and Table 1), and differentially expressed miRNAs in both GBM and BrM are discussed in detail below.…”

Section: Mirnas Differentially Regulated In Brain Cancermentioning

confidence: 99%

Therapeutically Significant MicroRNAs in Primary and Metastatic Brain Malignancies

Akilandeswari

Larcher

Chen

et al. 2020

Cancers

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Brain cancer is one among the rare cancers with high mortality rate that affects both children and adults. The most aggressive form of primary brain tumor is glioblastoma. Secondary brain tumors most commonly metastasize from primary cancers of lung, breast, or melanoma. The five-year survival of primary and secondary brain tumors is 34% and 2.4%, respectively. Owing to poor prognosis, tumor heterogeneity, increased tumor relapse, and resistance to therapies, brain cancers have high mortality and poor survival rates compared to other cancers. Early diagnosis, effective targeted treatments, and improved prognosis have the potential to increase the survival rate of patients with primary and secondary brain malignancies. MicroRNAs (miRNAs) are short noncoding RNAs of approximately 18–22 nucleotides that play a significant role in the regulation of multiple genes. With growing interest in the development of miRNA-based therapeutics, it is crucial to understand the differential role of these miRNAs in the given cancer scenario. This review focuses on the differential expression of ten miRNAs (miR-145, miR-31, miR-451, miR-19a, miR-143, miR-125b, miR-328, miR-210, miR-146a, and miR-126) in glioblastoma and brain metastasis. These miRNAs are highly dysregulated in both primary and metastatic brain tumors, which necessitates a better understanding of their role in these cancers. In the context of the tumor microenvironment and the expression of different genes, these miRNAs possess both oncogenic and/or tumor-suppressive roles within the same cancer.

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“…In the hypoxic microenvironment, miRNAs contribute to metabolic activities, to the maintenance of stemness in cancer cells and to therapy resistance. miRNAs, hypoxia and CSC are part of a complex signaling network that promotes tumor aggressiveness [170].…”

Section: The Role Of Mirnas In Cancer Stem Cells Metabolismmentioning

confidence: 99%

Metabolic Escape Routes of Cancer Stem Cells and Therapeutic Opportunities

Turdo

Porcelli

D'Accardo

et al. 2020

Cancers

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Although improvement in early diagnosis and treatment ameliorated life expectancy of cancer patients, metastatic disease still lacks effective therapeutic approaches. Resistance to anticancer therapies stems from the refractoriness of a subpopulation of cancer cells—termed cancer stem cells (CSCs)—which is endowed with tumor initiation and metastasis formation potential. CSCs are heterogeneous and diverge by phenotypic, functional and metabolic perspectives. Intrinsic as well as extrinsic stimuli dictated by the tumor microenvironment (TME)have critical roles in determining cell metabolic reprogramming from glycolytic toward an oxidative phenotype and vice versa, allowing cancer cells to thrive in adverse milieus. Crosstalk between cancer cells and the surrounding microenvironment occurs through the interchange of metabolites, miRNAs and exosomes that drive cancer cells metabolic adaptation. Herein, we identify the metabolic nodes of CSCs and discuss the latest advances in targeting metabolic demands of both CSCs and stromal cells with the scope of improving current therapies and preventing cancer progression.

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MicroRNAs, Hypoxia and the Stem-Like State as Contributors to Cancer Aggressiveness

Cited by 43 publications

References 256 publications

Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment

Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment

Therapeutically Significant MicroRNAs in Primary and Metastatic Brain Malignancies

Metabolic Escape Routes of Cancer Stem Cells and Therapeutic Opportunities

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