Is Mda‐7/IL‐24 a Potential Target and Biomarker for Enhancing Drug Sensitivity in Human Glioma U87 Cell Line?

Wang, Qin; Zhu, Yu; Yang, Ping

doi:10.1002/ar.22723

Cited by 6 publications

(5 citation statements)

References 18 publications

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“…Several secreted factors, including tumor-associated inflammatory cytokines were shown to regulate autocrine/paracrine signaling in mediating the malignant transformation of tumor cells including chemoresistance [26–28]. To explore the potential targets involving in MSI1-driven tumor-resistance in malignant glioma, we sought to in silico analyze the global gene expression profile to explore the impact of MSI1 overexpression in GBM cells.…”

Section: Resultsmentioning

confidence: 99%

Musashi-1 regulates AKT-derived IL-6 autocrinal/paracrinal malignancy and chemoresistance in glioblastoma

et al. 2016

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Glioblastoma multiform (GBM) is one of the most lethal human malignant brain tumors with high risks of recurrence and poor treatment outcomes. The RNA-binding protein Musashi-1 (MSI1) is a marker of neural stem/progenitor cells. Recent study showed that high expression level of MSI1 positively correlates with advanced grade of GBM, where MSI1 increases the growth of GBM. Herein, we explore the roles of MSI1 as well as the underlying mechanisms in the regulation of drug resistance and tumorigenesis of GBM cells. Our results demonstrated that overexpression of MSI1 effectively protected GBM cells from drug-induced apoptosis through down-regulating pro-apoptotic genes; whereas inhibition of AKT withdrew the MSI1-induced anti-apoptosis and cell survival. We further showed that MSI1 robustly promoted the secretion of the pro-inflammatory cytokine IL-6, which was governed by AKT activity. Autonomously, the secreted IL-6 enhanced AKT activity in an autocrine/paracrine manner, forming a positive feedback regulatory loop with the MSI1-AKT pathway. Our results conclusively demonstrated a novel drug resistance mechanism in GBM cells that MSI1 inhibits drug-induced apoptosis through AKT/IL6 regulatory circuit. MSI1 regulates both cellular signaling and tumor-microenvironmental cytokine secretion to create an intra- and intercellular niche for GBM to survive from chemo-drug attack.

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Section: Resultsmentioning

confidence: 99%

Musashi-1 regulates AKT-derived IL-6 autocrinal/paracrinal malignancy and chemoresistance in glioblastoma

et al. 2016

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“…Survivin is not always expressed in normal adult human tissues, but is expressed in many human cancers. It has been shown that survivin expression is closely associated with the degree of malignancy and prognosis of patients with cancers [ 38 , 39 ]. Our research showed that survivin expression levels were significantly decreased in mda-7/IL-24 over expressing cells, indicating that MDA-7/IL-24 is a negative regulator of survivin.…”

Section: Discussionmentioning

confidence: 99%

“…Our research showed that survivin expression levels were significantly decreased in mda-7/IL-24 over expressing cells, indicating that MDA-7/IL-24 is a negative regulator of survivin. Down regulation of Survivin increases the expression of caspases in cells, thus promoting apoptosis [ 38 ]. Activation of the family of caspases was known as a crucial mechanism for the induction of death signals to start apoptosis [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Interleukin-24-mediated antitumor effects against human glioblastoma via upregulation of P38 MAPK and endogenous TRAIL-induced apoptosis and LC3-II activation-dependent autophagy

et al. 2023

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Background Melanoma differentiation-associated gene 7 (Mda-7) encodes IL-24, which can induce apoptosis in cancer cells. A novel gene therapy approach to treat deadly brain tumors, recombinant mda-7 adenovirus (Ad/mda-7) efficiently kills glioma cells. In this study, we investigated the factors affecting cell survival and apoptosis and autophagy mechanisms that destroy glioma cells by Ad/IL-24. Methods Human glioblastoma U87 cell line was exposed to a multiplicity of infections of Ad/IL-24. Antitumor activities of Ad/IL-24 were assessed by cell proliferation (MTT) and lactate dehydrogenase (LDH) release analysis. Using flow cytometry, cell cycle arrest and apoptosis were investigated. Using the ELISA method, the tumor necrosis factor (TNF-α) level was determined as an apoptosis-promoting factor and Survivin level as an anti-apoptotic factor. The expression levels of TNF-related apoptosis inducing ligand(TRAIL) and P38 MAPK genes were assessed by the Reverse transcription-quantitative polymerase chain reaction(RT‑qPCR) method. The expression levels of caspase-3 and protein light chain 3-II (LC3-II) proteins were analyzed by flow cytometry as intervening factors in the processes of apoptosis and autophagy in the cell death signaling pathway, respectively. Results The present findings demonstrated that transduction of IL-24 inhibited cell proliferation and induced cell cycle arrest and cell apoptosis in glioblastoma. Compared with cells of the control groups, Ad/IL24-infected U87 cells exhibited significantly increased elevated caspase-3, and TNF-α levels, while the survivin expression was decreased. TRAIL was shown to be upregulated in tumor cells after Ad/IL-24 infection and studies of the apoptotic cascade regulators indicate that Ad/IL-24 could further enhance the activation of apoptosis through the TNF family of death receptors. In the current study, we demonstrate that P38 MAPK is significantly activated by IL-24 expression. In addition, the overexpression of mda-7/IL-24 in GBM cells induced autophagy, which was triggered by the upregulation of LC3-II. Conclusions Our study demonstrates the antitumor effect of IL-24 on glioblastoma and may be a promising therapeutic approach for GBM cancer gene therapy.

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“…In addition, interleukin-24 (IL-24) in glioma cells affects the sensitivity of gliomas to cisplatin by regulating the expression levels of P-gp and Bcl-2. IL-24 may be a biomarker predicting the sensitivity of gliomas to chemotherapy [ 69 ]. Peroxisome proliferator-activated receptor-γ (PPAR-γ) also plays an important role in regulating the sensitivity of glioma cells to cisplatin.…”

Section: Discussionmentioning

confidence: 99%

The Mechanisms of Current Platinum Anticancer Drug Resistance in the Glioma

Gareev

Yuan

et al. 2022

CPD

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Gliomas are the most common and malignant primary tumors of the central nervous system (CNS). Glioblastomas are the most malignant and aggressive form of primary brain tumors and account for the majority of brain tumor-related deaths. The current standard treatment for gliomas is surgical resection supplemented by postoperative chemotherapy. Platinum drugs are a class of chemotherapeutic drugs that affect the cell cycle, and the main site of action is the DNA of cells, which are common chemotherapeutic drugs in clinical practice. Chemotherapy with platinum drugs such as cisplatin, carboplatin, oxaliplatin, or a combination thereof is used to treat a variety of tumors. However, the results of gliomas chemotherapy are unsatisfactory, and resistance to platinum drugs is one of the important reasons. The resistance of gliomas to platinum drugs is the result of a combination of influencing factors. Decreased intracellular drug concentration, enhanced function of cell processing active products, enhanced repair ability of cellular DNA damage and blockage of related apoptosis pathways play an important role in it. It’s known that the pathogenic properties of glioma cells and the response of glioma towards platinum-based drugs are strongly influenced by non-coding RNAs, particularly, by microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). miRNAs and lncRNAs control drug sensitivity and the development of tumor resistance towards platinum drugs. This mini-review summarizes the resistance mechanisms of gliomas to platinum drugs, as well as molecules and therapies that can improve the sensitivity of gliomas to platinum drugs.

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Is Mda‐7/IL‐24 a Potential Target and Biomarker for Enhancing Drug Sensitivity in Human Glioma U87 Cell Line?

Cited by 6 publications

References 18 publications

Musashi-1 regulates AKT-derived IL-6 autocrinal/paracrinal malignancy and chemoresistance in glioblastoma

Musashi-1 regulates AKT-derived IL-6 autocrinal/paracrinal malignancy and chemoresistance in glioblastoma

Interleukin-24-mediated antitumor effects against human glioblastoma via upregulation of P38 MAPK and endogenous TRAIL-induced apoptosis and LC3-II activation-dependent autophagy

The Mechanisms of Current Platinum Anticancer Drug Resistance in the Glioma

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