Transfer of Extracellular Vesicle-Associated-RNAs Induces Drug Resistance in ALK-Translocated Lung Adenocarcinoma

Kwok, Hoi‐Hin; Ning, Ziyu; Chong, Peony W C; Wan, T. S. K.; Ng, Margaret H.L.; Ho, Gloria Y.F.; Ip, Mary Sau-Man; Lam, David Chi‐Leung

doi:10.3390/cancers11010104

Cited by 23 publications

(19 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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: 53%

“…In lung adenocarcinoma, one of the differentially expressed miRNAs in EVs released from drug-resistant cells is miR-486-3p. 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).…”

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

confidence: 99%

See 1 more Smart Citation

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

Seo

Moeng

Sim³

et al. 2019

Cells

View full text Add to dashboard Cite

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...

show abstract

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

confidence: 53%

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

View full text Add to dashboard Cite

show abstract

“…In contrast to the previous section, studies also exist which describe the role of miRNA-486 in chemo-resistance. Extracellular vesicles (EVs) produced by ALK-translocated lung adenocarcinoma cell lines, which were rendered resistant to the ALK-TKIs crizotinib or ceretinib, were found to contain elevated levels of miRNA-486 amongst other non-coding RNAs [86]. When applied to drug-sensitive cell lines, the miRNA-486-containing EVs conferred resistance to both TKIs.…”

Section: Increased Mirna-486 Levels Promote Resistance To Treatment Imentioning

confidence: 99%

MiRNAs as Novel Adipokines: Obesity-Related Circulating MiRNAs Influence Chemosensitivity in Cancer Patients

Withers

Dewhurst

Hammond

et al. 2020

ncRNA

View full text Add to dashboard Cite

Adipose tissue is an endocrine organ, capable of regulating distant physiological processes in other tissues via the release of adipokines into the bloodstream. Recently, circulating adipose-derived microRNAs (miRNAs) have been proposed as a novel class of adipokine, due to their capacity to regulate gene expression in tissues other than fat. Circulating levels of adipokines are known to be altered in obese individuals compared with typical weight individuals and are linked to poorer health outcomes. For example, obese individuals are known to be more prone to the development of some cancers, and less likely to achieve event-free survival following chemotherapy. The purpose of this review was twofold; first to identify circulating miRNAs which are reproducibly altered in obesity, and secondly to identify mechanisms by which these obesity-linked miRNAs might influence the sensitivity of tumors to treatment. We identified 8 candidate circulating miRNAs with altered levels in obese individuals (6 increased, 2 decreased). A second literature review was then performed to investigate if these candidates might have a role in mediating resistance to cancer treatment. All of the circulating miRNAs identified were capable of mediating responses to cancer treatment at the cellular level, and so this review provides novel insights which can be used by future studies which aim to improve obese patient outcomes.

show abstract

“…This combination, however, is not always successful. EVs from various origins operate in chemotherapy drug resistance by participating in various processes, such as expression of glutathione S-transferase or other enzymes; sequestration of cytotoxic drugs; capture of monoclonal antibodies by their binding to membrane proteins; and release to the cancer cell cytoplasm of specific proteins together with various coding and non-coding RNAs (see, among others, [ [72,73]]). These effects are at least potentially critical because, together with the cross-talk of cancer cells with stromal cells, they play substantial roles in the establishment of cancer.…”

Section: Diagnosis and Therapymentioning

confidence: 99%

Extracellular vesicles, news about their role in immune cells: physiology, pathology and diseases

Meldolesi

2019

Clinical and Experimental Immunology

View full text Add to dashboard Cite

Two types of extracellular vesicles (EVs), exosomes and ectosomes, are generated and released by all cells, including immune cells. The two EVs appear different in many properties: size, mechanism and site of assembly, composition of their membranes and luminal cargoes, sites and processes of release. In functional terms, however, these differences are minor. Moreover, their binding to and effects on target cells appear similar, thus the two types are considered distinct only in a few cases, otherwise they are presented together as EVs. The EV physiology of the various immune cells differs as expected from their differential properties. Some properties, however, are common: EV release, taking place already at rest, is greatly increased upon cell stimulation; extracellular navigation occurs adjacent and at distance from the releasing cells; binding to and uptake by target cells are specific. EVs received from other immune or distinct cells govern many functions in target cells. Immune diseases in which EVs play multiple, often opposite (aggression and protection) effects, are numerous; inflammatory diseases; pathologies of various tissues; and brain diseases, such as multiple sclerosis. EVs also have effects on interactive immune and cancer cells. These effects are often distinct, promoting cytotoxicity or proliferation, the latter together with metastasis and angiogenesis. Diagnoses depend on the identification of EV biomarkers; therapies on various mechanisms such as (1) removal of aggression-inducing EVs; (2) EV manipulations specific for single targets, with insertion of surface peptides or luminal miRNAs; and (3) removal or re-expression of molecules from target cells.

show abstract

Transfer of Extracellular Vesicle-Associated-RNAs Induces Drug Resistance in ALK-Translocated Lung Adenocarcinoma

Cited by 23 publications

References 42 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

MiRNAs as Novel Adipokines: Obesity-Related Circulating MiRNAs Influence Chemosensitivity in Cancer Patients

Extracellular vesicles, news about their role in immune cells: physiology, pathology and diseases

Contact Info

Product

Resources

About