Contribution of microRNAs to radio- and chemoresistance of brain tumors and their therapeutic potential

Chistiakov, Dimitry A.; Chekhonin, V. P.

doi:10.1016/j.ejphar.2012.03.031

Cited by 54 publications

(28 citation statements)

References 141 publications

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“…Some up-regulated miRNAs in brain tumors are believed to play a pro-oncogenic role via supporting growth, proliferation, migration, and survival of cancer cells while expression of other miRNA having anti-tumor effects is suppressed in gliomas. These miRNAs harbor a therapeutic significance as therapeutic agents in anti-cancer therapy (Lawler and Chiocca, 2009; Godlewski et al, 2010b; Chistiakov and Chekhonin, 2012). Godlewski et al (2010a) illustrated glucose regulation of proliferation and migration of glioma cells: (i) low glucose ⇒ down-regulation of miR-451 and up-regulation of the AMPK complex ⇒ cell migration (ii) normal (high) glucose ⇒ up-regulation of miR-451 and down-regulation of AMPK complex ⇒ proliferation.…”

Section: Discussionmentioning

confidence: 99%

Regulation of Cell Proliferation and Migration in Glioblastoma: New Therapeutic Approach

Kim

2013

Front. Oncol.

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Glioblastoma is the most aggressive brain cancer with the poor survival rate. A microRNA, miR-451, and its downstream molecules, CAB39/LKB1/STRAD/AMPK, are known to play a critical role in regulating a biochemical balance between rapid proliferation and invasion in the presence of metabolic stress in microenvironment. We develop a novel multi-scale mathematical model where cell migration and proliferation are controlled through a core intracellular control system (miR-451-AMPK complex) in response to glucose availability and physical constraints in the microenvironment. Tumor cells are modeled individually and proliferation and migration of those cells are regulated by the intracellular dynamics and reaction-diffusion equations of concentrations of glucose, chemoattractant, extracellular matrix, and MMPs. The model predicts that invasion patterns and rapid growth of tumor cells after conventional surgery depend on biophysical properties of cells, dynamics of the core control system, and microenvironment as well as glucose injection methods. We developed a new type of therapeutic approach: effective injection of chemoattractant to bring invasive cells back to the surgical site after initial surgery, followed by glucose injection at the same location. The model suggests that a good combination of chemoattractant and glucose injection at appropriate time frames may lead to an effective therapeutic strategy of eradicating tumor cells.

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Section: Discussionmentioning

confidence: 99%

Regulation of Cell Proliferation and Migration in Glioblastoma: New Therapeutic Approach

Kim

2013

Front. Oncol.

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“…It has been shown that miRNAs such as miRNA-128 (Godlewski et al, 2008), miRNA-124 (Xia et al, 2012), miRNA-146a (Mei et al, 2011) and miRNA-34a (Guessous et al, 2010) regulate the stem cell phenotype in GSCs and may contribute to gliomagenesis (reviewed in (Zhang et al, 2012)). As GSCs are known to be involved in chemo- and radiotherapy, several reports have analyzed the effects of miRNAs on this process and found that, among others, miRNA-124 (Yang et al, 2012), miRNA-125b (Shi et al, 2012) and miR-9* (Jeon et al, 2011) contribute by regulating mostly known mediators of chemo- or radiotherapy resistance (reviewed in (Chistiakov and Chekhonin, 2012)). As it turns out in GSCs, epigenetic mechanisms such as DNA methylation (Asuthkar et al, 2012) and histone modifications (Katsushima et al, 2012) can also regulate miRNA expression, and in turn miRNAs can regulate epigenetic modifying genes such as Bmi1 (Godlewski et al, 2008), adding to the complexity of epigenetic regulation in GSCs.…”

Section: Epigenetic Regulation Of Gscsmentioning

confidence: 99%

Brain tumor stem cells: Molecular characteristics and their impact on therapy

Schonberg

Lubelski

Miller

et al. 2014

Molecular Aspects of Medicine

166

153

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Glioblastoma (GBM) is the most prevalent primary brain tumor and ranks among the most lethal of human cancers with conventional therapy offering only palliation. Great strides have been made in understanding brain cancer genetics and modeling these tumors with new targeted therapies being tested but these advances have not translated into substantially improved patient outcomes. Multiple chemotherapeutic agents, including temozolomide, the first-line treatment for glioblastoma, have been developed to kill cancer cells. However, the response to temozolomide in GBM is modest. Radiation is also moderately effective but this approach is plagued by limitations due to collateral radiation damage to healthy brain tissue and development of radioresistance. Therapeutic resistance is attributed at least in part to a cell population within the tumor that possesses stem-like characteristics and tumor propagating capabilities, referred to as cancer stem cells. Within GBM, the intratumoral heterogeneity is derived from a combination of regional genetic variance and a cellular hierarchy often regulated by distinct cancer stem cell niches, most notably perivascular and hypoxic regions. With the recent emergence as a key player in tumor biology, cancer stem cells have symbiotic relationships with the tumor microenvironment, oncogenic signaling pathways, and epigenetic modifications. The origins of cancer stem cells and their contributions to brain tumor growth and therapeutic resistance are under active investigation with novel anti-cancer stem cell therapies offering potential new hope for this lethal disease.

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“…Dysregulation of miRNAs plays critical roles in many human physiological and pathological processes such as proliferation, differentiation, morphogenesis and tumourigenesis [14]. Many reports have exhibited a role for miRNAs in the pathogenesis and aetiology of cancer, including chemoresistance, EMT and cancer stem cells [15][16][17]. To further explore chemoresistant mechanisms and provide theoretical support for chemoresistant reversal by chemotherapeutic agents, docetaxelresistant human LAD cell lines (SPC-A1/DTX and H1299/DTX) were previously established, and we identified a distinctive miRNA expression pattern between docetaxel-resistant LAD cell lines and parental LAD cell lines [18].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-451 induces epithelial–mesenchymal transition in docetaxel-resistant lung adenocarcinoma cells by targeting proto-oncogene c-Myc

Chen¹,

Huang²,

Zhang³

et al. 2014

European Journal of Cancer

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Contribution of microRNAs to radio- and chemoresistance of brain tumors and their therapeutic potential

Cited by 54 publications

References 141 publications

Regulation of Cell Proliferation and Migration in Glioblastoma: New Therapeutic Approach

Regulation of Cell Proliferation and Migration in Glioblastoma: New Therapeutic Approach

Brain tumor stem cells: Molecular characteristics and their impact on therapy

MicroRNA-451 induces epithelial–mesenchymal transition in docetaxel-resistant lung adenocarcinoma cells by targeting proto-oncogene c-Myc

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