The Role of microRNAs in Multidrug Resistance of Glioblastoma

Mahinfar, Parvaneh; Mansoori, Behnaz; Rostamzadeh, Davoud; Baradaran, Behzad; Cho, William C.; Mansoori, Behzad

doi:10.3390/cancers14133217

Cited by 16 publications

(9 citation statements)

References 184 publications

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“…In another study, BDMC was used to reverse MDR in cisplatin-resistant non-small cell lung cancer by inhibition of CA916798 mRNA and protein and PI3K/AKT activities [ 61 ]. Despite advances and new strategies for treating GBM, MDR is a significant cause of failure for commonly used chemotherapeutic agents, including temozolomide (TMZ) [ 62 , 63 ]. Other causes include innate tumor cell resistance, inadequate drug concentration due to the blood–brain–tumor barrier, molecular heterogeneity, and clinical trials of new drugs in small groups [ 64 ].…”

Section: Resultsmentioning

confidence: 99%

Natural Compounds in Liposomal Nanoformulations of Potential Clinical Application in Glioblastoma

Piwowarczyk

Mlynarczyk

Krajka‐Kuźniak

et al. 2022

Cancers

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Glioblastoma (GBM) is the most common malignant neoplasm in adults among all CNS gliomas, with the 5-year survival rate being as low as 5%. Among nanocarriers, liposomal nanoformulations are considered as a promising tool for precise drug delivery. The herein presented study demonstrates the possibility of encapsulating four selected natural compounds (curcumin, bisdemethoxycurcumin, acteoside, and orientin) and their mixtures in cationic liposomal nanoformulation composed of two lipid types (DOTAP:POPC). In order to determine the physicochemical properties of the new drug carriers, specific measurements, including particle size, Zeta Potential, and PDI index, were applied. In addition, NMR and EPR studies were carried out for a more in-depth characterization of nanoparticles. Within biological research, the prepared formulations were evaluated on T98G and U-138 MG glioblastoma cell lines in vitro, as well as on a non-cancerous human lung fibroblast cell line (MRC-5) using the MTT test to determine their potential as anticancer agents. The highest activity was exhibited by liposome-entrapped acteoside towards the T98G cell line with IC50 equal 2.9 ± 0.9 µM after 24 hours of incubation. Noteworthy, curcumin and orientin mixture in liposomal formulation exhibited a synergistic effect against GBM. Moreover, the impact on the expression of apoptosis-associated proteins (p53 and Caspase-3) of acteoside as well as curcumin and orientin mixture, as the most potent agents, was assessed, showing nearly 40% increase as compared to control U-138 MG and T98G cells. It should be emphasized that a new and alternative method of extrusion of the studied liposomes was developed.

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Section: Resultsmentioning

confidence: 99%

Natural Compounds in Liposomal Nanoformulations of Potential Clinical Application in Glioblastoma

Piwowarczyk

Mlynarczyk

Krajka‐Kuźniak

et al. 2022

Cancers

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“…For instance, miR-33b was lowly expressed in BC tissues and suppressed the EMT progress and invasion of BC despite targeting HMGA2, spalt-like transcription factor 4 (SALL4), and twist family bHLH transcription factor 1 (TWIST1) (94). Furthermore, acting as a negative regulatory factor, miR-143-5p could decrease VIM and CDH2 protein expression and increase CDH1 protein expression by directly targeting HMGA2 (95). Research that focused on the effects of modifications on miRNA has demonstrated that N6-methyladenosine modification of RNAs is crucial for cancer progression (96).…”

Section: Breast Cancermentioning

confidence: 99%

HMGA2 promotes cancer metastasis by regulating epithelial–mesenchymal transition

Ma,

Ye,

Liu

et al. 2024

Front. Oncol.

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Epithelial–mesenchymal transition (EMT) is a complex physiological process that transforms polarized epithelial cells into moving mesenchymal cells. Dysfunction of EMT promotes the invasion and metastasis of cancer. The architectural transcription factor high mobility group AT-hook 2 (HMGA2) is highly overexpressed in various types of cancer (e.g., colorectal cancer, liver cancer, breast cancer, uterine leiomyomas) and significantly correlated with poor survival rates. Evidence indicated that HMGA2 overexpression markedly decreased the expression of epithelial marker E-cadherin (CDH1) and increased that of vimentin (VIM), Snail, N-cadherin (CDH2), and zinc finger E-box binding homeobox 1 (ZEB1) by targeting the transforming growth factor beta/SMAD (TGFβ/SMAD), mitogen-activated protein kinase (MAPK), and WNT/beta-catenin (WNT/β-catenin) signaling pathways. Furthermore, a new class of non-coding RNAs (miRNAs, circular RNAs, and long non-coding RNAs) plays an essential role in the process of HMGA2-induced metastasis and invasion of cancer by accelerating the EMT process. In this review, we discuss alterations in the expression of HMGA2 in various types of cancer. Furthermore, we highlight the role of HMGA2-induced EMT in promoting tumor growth, migration, and invasion. More importantly, we discuss extensively the mechanism through which HMGA2 regulates the EMT process and invasion in most cancers, including signaling pathways and the interacting RNA signaling axis. Thus, the elucidation of molecular mechanisms that underlie the effects of HMGA2 on cancer invasion and patient survival by mediating EMT may offer new therapeutic methods for preventing cancer progression.

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“…Based on the level of individual miRNAs, the miRNAs with the highest prognostic value for GBM were selected [ 72 ], indicating that that the diagnosis of GBM is also possible on the basis of the analysis of miRNA from the blood and cerebrospinal fluid of patients [ 73 , 74 , 75 ]. Functional analysis of individual GBM-specific miRNAs indicates that they can act as both oncogenes and tumor suppressors, are responsible for developing resistance to chemotherapy and radiotherapy, stimulate neo-angiogenesis and cell proliferation, and regulate the cell cycle and apoptosis [ 76 , 77 , 78 , 79 , 80 ] ( Table 2 ).…”

Section: Mirnas Expression In Gbmmentioning

confidence: 99%

microRNAs (miRNAs) in Glioblastoma Multiforme (GBM)—Recent Literature Review

Makowska

Smolarz

Romanowicz

2023

IJMS

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Glioblastoma multiforme (GBM) is the most common, malignant, poorly promising primary brain tumor. GBM is characterized by an infiltrating growth nature, abundant vascularization, and a rapid and aggressive clinical course. For many years, the standard treatment of gliomas has invariably been surgical treatment supported by radio- and chemotherapy. Due to the location and significant resistance of gliomas to conventional therapies, the prognosis of glioblastoma patients is very poor and the cure rate is low. The search for new therapy targets and effective therapeutic tools for cancer treatment is a current challenge for medicine and science. microRNAs (miRNAs) play a key role in many cellular processes, such as growth, differentiation, cell division, apoptosis, and cell signaling. Their discovery was a breakthrough in the diagnosis and prognosis of many diseases. Understanding the structure of miRNAs may contribute to the understanding of the mechanisms of cellular regulation dependent on miRNA and the pathogenesis of diseases underlying these short non-coding RNAs, including glial brain tumors. This paper provides a detailed review of the latest reports on the relationship between changes in the expression of individual microRNAs and the formation and development of gliomas. The use of miRNAs in the treatment of this cancer is also discussed.

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The Role of microRNAs in Multidrug Resistance of Glioblastoma

Cited by 16 publications

References 184 publications

Natural Compounds in Liposomal Nanoformulations of Potential Clinical Application in Glioblastoma

Natural Compounds in Liposomal Nanoformulations of Potential Clinical Application in Glioblastoma

HMGA2 promotes cancer metastasis by regulating epithelial–mesenchymal transition

microRNAs (miRNAs) in Glioblastoma Multiforme (GBM)—Recent Literature Review

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