miR-1268a regulates ABCC1 expression to mediate temozolomide resistance in glioblastoma

Li, Yaomin; Liu, Yawei; Ren, Jing; Deng, Shengze; Yi, Guozhong; Guo, Manlan; Shu, Songren; Zhao, Liang; Peng, Yu‐Ping; Qi, Songtao

doi:10.1007/s11060-018-2835-3

Cited by 55 publications

(24 citation statements)

References 36 publications

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“…Splicing events with a p -value< 0.01 in the log-rank test were regarded as prognostic. The same strategy was performed in additional studies, including survival analysis for splicing subgroups and splicing factors, as described in our former study [17–19].…”

Section: Methodsmentioning

confidence: 99%

Classification of glioma based on prognostic alternative splicing

Ren

Peng

et al. 2019

BMC Med Genomics

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BackgroundPreviously developed classifications of glioma have provided enormous advantages for the diagnosis and treatment of glioma. Although the role of alternative splicing (AS) in cancer, especially in glioma, has been validated, a comprehensive analysis of AS in glioma has not yet been conducted. In this study, we aimed at classifying glioma based on prognostic AS.MethodsUsing the TCGA glioblastoma (GBM) and low-grade glioma (LGG) datasets, we analyzed prognostic splicing events. Consensus clustering analysis was conducted to classified glioma samples and correlation analysis was conducted to characterize regulatory network of splicing factors and splicing events.ResultsWe analyzed prognostic splicing events and proposed novel splicing classifications across pan-glioma samples (labeled pST1–7) and across GBM samples (labeled ST1–3). Distinct splicing profiles between GBM and LGG were observed, and the primary discriminator for the pan-glioma splicing classification was tumor grade. Subtype-specific splicing events were identified; one example is AS of zinc finger proteins, which is involved in glioma prognosis. Furthermore, correlation analysis of splicing factors and splicing events identified SNRPB and CELF2 as hub splicing factors that upregulated and downregulated oncogenic AS, respectively.ConclusionA comprehensive analysis of AS in glioma was conducted in this study, shedding new light on glioma heterogeneity and providing new insights into glioma diagnosis and treatment.

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Section: Methodsmentioning

confidence: 99%

Classification of glioma based on prognostic alternative splicing

Ren

Peng

et al. 2019

BMC Med Genomics

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“…Over-expression of miR-595 can either decrease or increase the efficacy of methotrexate or cisplatin, respectively [30,31] miR-1268a ABCC1 Glioblastoma Over-expression of miR-1268a augments temozolomide sensitivity [24] Cells 2020, 9, 29 6 of 32…”

Section: Acute Lymphoblastic Leukemia Ovarian Cancermentioning

confidence: 99%

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Seo

Moeng

Sim³

et al. 2019

Cells

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The susceptibility of cancer cells to different types of treatments can be restricted by intrinsic and acquired therapeutic resistance, leading to the failure of cancer regression and remission. To overcome this problem, a combination therapy has been proposed as a fundamental strategy to improve therapeutic responses; however, resistance is still unavoidable. MicroRNA (miRNAs) are associated with cancer therapeutic resistance. The modulation of dysregulated miRNA levels through miRNA-based therapy comprising a replacement or inhibition approach has been proposed to sensitize cancer cells to other anti-cancer therapies. The combination of miRNA-based therapy with other anti-cancer therapies (miRNA-based combinatorial cancer therapy) is attractive, due to the ability of miRNAs to target multiple genes associated with the signaling pathways controlling therapeutic resistance. In this article, we present an overview of recent findings on the role of therapeutic resistance-related miRNAs in different types of cancer. We review the feasibility of utilizing dysregulated miRNAs in cancer cells and extracellular vesicles as potential candidates for miRNA-based combinatorial cancer therapy. We also discuss innate properties of miRNAs that need to be considered for more effective combinatorial cancer therapy.Cells 2020, 9, 29 2 of 32 to confer the ability to acquire CSC properties onto cancer cells, thereby contributing to therapeutic resistance [7]. Moreover, cell-to-cell communication via extracellular vesicles among different types of cells within the cancer microenvironment could affect the efficacy of cancer therapies by delivering miRNAs that regulate various signaling pathways connected to therapeutic resistance [8,9].Combination therapies have been proposed to overcome therapeutic resistance via the combined inhibition of different mechanisms. For example, the combination of cobimetinib and pictilisib was reported to be beneficial for the treatment of colorectal cancer cells. However, resistance is unavoidable even after the combination treatment [10]. Similarly, the simultaneous inhibition of phosphoinositide 3-kinase (PI3K) and a mechanistic target of rapamycin kinase (mTOR) was reported to activate extracellular signal-regulated kinase (ERK), a pro-survival factor, in acute myeloid leukemia [11]. Therefore, it is still necessary to explore new combination strategies to defeat therapeutic resistance. An improved understanding of the cellular basis of cancer therapeutic resistance can further provide promising opportunities to design and develop novel cancer treatment strategies to manage cancers.MicroRNAs (miRNAs) are widely recognized, small, regulatory RNAs modulating numerous intracellular signaling pathways in several diseases, including cancers. Based on the expression levels and intracellular functions of miRNAs, they could act as tumor-suppressive or oncogenic factors in cancer cells [12][13][14]. The abnormal expression of miRNAs is associated with therapeutic resistance in cancer, and the modulation of m...

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“…However, these results warrant further investigation addressing the specific functions of these two rarely characterized miRNAs. Interestingly, unlike the miRNAs identified in the total plasma, which are mostly tumor suppressors, many miRNAs contained in the sEVs have previously shown oncogenic functions (miR-1268a, miR-4258, miR-1246, miR-660, miR373) [61][62][63][64][65][66]. Among the multiple strategies developed by cancer cells to gain a survival advantage, sEVs are, indeed, one of the most concealed.…”

Section: Discussionmentioning

confidence: 99%

Circulating miRNAs in Small Extracellular Vesicles Secreted by a Human Melanoma Xenograft in Mouse Brains

Guglielmi

Nardella

Musa

et al. 2020

Cancers

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The identification of liquid biomarkers remains a major challenge to improve the diagnosis of melanoma patients with brain metastases. Circulating miRNAs packaged into tumor-secreted small extracellular vesicles (sEVs) contribute to tumor progression. To investigate the release of tumor-secreted miRNAs by brain metastasis, we developed a xenograft model where human metastatic melanoma cells were injected intracranially in nude mice. The comprehensive profiles of both free miRNAs and those packaged in sEVs secreted by the melanoma cells in the plasma demonstrated that most (80%) of the sEV-associated miRNAs were also present in serum EVs from a cohort of metastatic melanomas, included in a publicly available dataset. Remarkably, among them, we found three miRNAs (miR-224-5p, miR-130a-3p and miR-21-5p) in sEVs showing a trend of upregulation during melanoma progression. Our model is proven to be valuable for identifying miRNAs in EVs that are unequivocally secreted by melanoma cells in the brain and could be associated to disease progression.

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miR-1268a regulates ABCC1 expression to mediate temozolomide resistance in glioblastoma

Abstract: Through RNA-seq analysis, we discovered miR-1268a and elucidated its role in modulating TMZ-resistance of GBM cells by targeting ABCC1.

Cited by 55 publications

References 36 publications

Classification of glioma based on prognostic alternative splicing

Classification of glioma based on prognostic alternative splicing

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Circulating miRNAs in Small Extracellular Vesicles Secreted by a Human Melanoma Xenograft in Mouse Brains

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