MicroRNA-17 inhibition overcomes chemoresistance and suppresses epithelial-mesenchymal transition through a DEDD-dependent mechanism in gastric cancer

Wu, Dongmei; Hong, Xi; Wang, Lingling; Cui, Xia-Feng; Lü, Jun; Chen, Guiquan; Zheng, Yuxin

doi:10.1016/j.biocel.2018.06.007

Cited by 27 publications

(14 citation statements)

References 34 publications

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“…Death-effector domain-containing DNA-binding protein (DEDD) inversely controls the process of EMT by attenuating the expression of EMT-promoting elements, such as SNAI1 and Twist family BHLH transcription factors (Twist) [171]. In gastric cancer cells, a reduction in miR-17-5p interrupts the EMT process by up-regulating its target, DEDD, thereby affecting the therapeutic resistance of gastric cancer cells [161] (Table 5).…”

Section: Mirnas Indirectly Regulating Emt-related Transcription Factorsmentioning

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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Section: Mirnas Indirectly Regulating Emt-related Transcription Factorsmentioning

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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“…EMT‐expressing cancer cells showed decreased expression of epithelial cell markers such as E‐cadherin and ZO‐1, while expression of mesenchymal cell markers such as vimentin and N‐cadherin increased. Although there is increasing evidence that EMT is closely related to the development of drug resistance in gastric cancer cells, its underlying mechanisms have not yet been fully elucidated …”

Section: Introductionmentioning

confidence: 99%

“…Although there is increasing evidence that EMT is closely related to the development of drug resistance in gastric cancer cells, its underlying mechanisms have not yet been fully elucidated. [14][15][16] To date, many studies have investigated the role of oestrogen receptor (ER) in gastric cancer, and the possible mechanisms of these effects and the clinical relevance of dysregulated ER in GC.…”

Section: Introductionmentioning

confidence: 99%

Cisplatin resistance in gastric cancer cells is involved with GPR30‐mediated epithelial‐mesenchymal transition

Wang

Sun

et al. 2020

J Cellular Molecular Medi

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Cisplatin is the major chemotherapeutic drug in gastric cancer, particularly in treating advanced gastric cancer. Tumour cells often develop resistance to chemotherapeutic drugs, which seriously affects the efficacy of chemotherapy. GPR30 is a novel oestrogen receptor that is involved in the invasion, metastasis and drug resistance of many tumours. Targeting GPR30 has been shown to increase the drug sensitivity of breast cancer cells. However, few studies have investigated the role of GPR30 in gastric cancer. Epithelial‐mesenchymal transition (EMT) has been shown to be associated with the development of chemotherapeutic drug resistance. In this study, we demonstrated that GPR30 is involved in cisplatin resistance by promoting EMT in gastric cancer. GPR30 knockdown resulted in increased sensitivity of different gastric cancer (GC) cells to cisplatin and alterations in the epithelial/mesenchymal markers. Furthermore, G15 significantly enhanced the cisplatin sensitivity of GC cells while G1 inhibited this phenomenon. In addition, EMT occurred when AGS and BGC‐823 were treated with cisplatin. Down‐regulation of GPR30 with G15 inhibited this transformation, while G1 promoted it. Taken together, these results revealed the role of GPR30 in the formation of cisplatin resistance, suggesting that targeting GPR30 signalling may be a potential strategy for improving the efficacy of chemotherapy in gastric cancer.

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“…Similarly, miR-193-3p and miR-147 could promote 5-FU resistance of gastric cancer cells via directly suppressing their target gene PTEN [127,128]. Oncogenic miR-17 has been found to reduce 5-FU sensitivity of gastric cancer cells through silencing expression of DEDD [129].…”

Section: Mirnas and Resistance To Platinum Drugsmentioning

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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MicroRNA-17 inhibition overcomes chemoresistance and suppresses epithelial-mesenchymal transition through a DEDD-dependent mechanism in gastric cancer

Cited by 27 publications

References 34 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

Cisplatin resistance in gastric cancer cells is involved with GPR30‐mediated epithelial‐mesenchymal transition

Noncoding RNAs in gastric cancer: implications for drug resistance

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