Exosomal transfer of miR-501 confers doxorubicin resistance and tumorigenesis via targeting of BLID in gastric cancer

Liu, Xu; Lü, Ying; Yu, Xu; Hou, Sizhu; Huang, Jiehong; Wang, Bo; Zhao, Jie; Xia, Shilin; Fan, Shujun; Yu, Xiaotang; Du, Ye; Hou, Li; Li, Zhiyue; Ding, Zijie; An, Shuo; Huang, Bo; Li, Lianhong; Tang, Jianwu; Ju, Jingfang; Guan, Hongwei; Song, Bo

doi:10.1016/j.canlet.2019.05.035

Cited by 84 publications

(58 citation statements)

References 64 publications

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“…Exosomes containing miR-222-3p are transferred to other cancer cells, where miR-222-3p directly regulates SOCS3 and develops malignant phenotypes of lung cancer cells along with gemcitabine resistance [183]. In addition, the therapeutic resistance to imatinib could be triggered by exosomal miR-365, which targets Bcl-2 associated X (BAX) in CML cells [184] (Figure 3 Consistent with the above observations, other studies found that exosomal miRNAs, miR-432a-5p, miR-486-3p, and miR-501-5p, could be derived from drug-resistant cancer cells, and these miRNAs develop the resistance in surrounding cells [185][186][187]. Exosomal miR-432a-5p transmits palbociclib resistance to other cancer cells via down-regulating SMAD4 and subsequently inducing CDK6 expression in breast cancer cells [185].…”

Section: Mir-222-3p and Mir-365supporting

confidence: 54%

“…The delivery of miR-486-3p into surrounding cancer cells causes a down-regulation of PTEN and a development of resistance toward tyrosine kinase inhibitors [186]. Also, by targeting the BH3-like motif containing an inducer of cell death (BLID), exosomal miR-501-5p activates Akt signaling and represses caspase activation in recipient cells, eventually contributing to doxorubicin resistance in gastric cancer cells [187] (Figure 3). Overall, these results clearly indicate that knockdown of extracellular vesicle miRNAs has a therapeutic benefit in several cancer types.…”

Section: Mir-222-3p and Mir-365mentioning

confidence: 99%

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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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Section: Mir-222-3p and Mir-365supporting

confidence: 54%

Section: Mir-222-3p and Mir-365mentioning

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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“…Additionally, miR-501 was also identified in SGC7901/ADR cells-secreted exosomes (ADR Exo) with a relatively high level. Exosome transferred miR-501 could promote tumorigenesis and ADR resistance through down-regulating BLID expression, and subsequently, inactivating phosphorylation of AKT and caspase-9/-3 [59]. MiR-20a was also proved to enhance gastric cancer resistance to ADR via inhibiting expression of early growth response 2 (EGR2), a member of a multi-gene family which encoding C2H2type zinc-finger proteins [60].…”

Section: Mirnas and Adr Resistancementioning

confidence: 99%

Noncoding RNAs in gastric cancer: implications for drug resistance

et al. 2020

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Gastric cancer is the fourth most common malignancy and the third leading cause of cancer-related deaths worldwide. Advanced gastric cancer patients can notably benefit from chemotherapy including adriamycin, platinum drugs, 5-fluorouracil, vincristine, and paclitaxel as well as targeted therapy drugs. Nevertheless, primary drug resistance or acquisition drug resistance eventually lead to treatment failure and poor outcomes of the gastric cancer patients. The detailed mechanisms involved in gastric cancer drug resistance have been revealed. Interestingly, different noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), are critically involved in gastric cancer development. Multiple lines of evidences demonstrated that ncRNAs play a vital role in gastric cancer resistance to chemotherapy reagents and targeted therapy drugs. In this review, we systematically summarized the emerging role and detailed molecular mechanisms of ncRNAs impact drug resistance of gastric cancer. Additionally, we propose the potential clinical implications of ncRNAs as novel therapeutic targets and prognostic biomarkers for gastric cancer.

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“…Lobb et al 4 demonstrated that mesenchymal nonsmall cell lung cancer (NSCLC) cells changed the chemotherapy tolerance of recipient cells with increased expressed exosomal ZEB1 mRNA (Table 1). Liu et al 5 observed overexpressed exosomal miR-501 in doxorubicin-tolerant gastric cancer (GC) cell and proposed that miR-501 suppressed BLID and inhibited caspase-9/caspase-3 and phosphorylation of Akt (Table 1), offering an exploitable target miR-501 for drug-resistant GC availably. Tumor-related stroma cells can also release exosomes to activate antiviral/NOTCH3 pathways which contribute to breast cancer therapy resistance.…”

Section: Therapy Resistancementioning

confidence: 99%

The cancer exosomes: Clinical implications, applications and challenges

Tang

Hou

et al. 2019

Intl Journal of Cancer

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The exosome is a small functional vesicle enriched in selected proteins, lipids and nucleic acids, displaying distinct molecular heterogeneity. Exosomes released can transform the extracellular matrix microenvironments, transmit signals and molecules to recipient cells and trigger changes in their pathophysiological functions. Tumor‐derived exosomes mediate the interactions of tumor cells and microenvironment significantly, and they stimulate tumor growth and development through specific signaling pathways related to metastasis, therapeutic resistance and immunosuppression. Exosome biogenesis from tumors often represents abundant biological information, and novel and efficient isolation and detection methods of exosomes provide a promising approach for tumor diagnosis and prognosis estimation. Moreover, exosome can even be developed as therapeutic agents for multiple disease models based on effective material transport characteristics and biofilm specificity. This review reports the clinical implications and challenges of exosomes in cancer progression, therapy resistance, metastasis and immune escape, and underlying cancerogenic pathological phenotypes including fibrosis and viral infection.

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Exosomal transfer of miR-501 confers doxorubicin resistance and tumorigenesis via targeting of BLID in gastric cancer

Cited by 84 publications

References 64 publications

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

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

Noncoding RNAs in gastric cancer: implications for drug resistance

The cancer exosomes: Clinical implications, applications and challenges

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