MiR-199a-3p enhances cisplatin sensitivity of cholangiocarcinoma cells by inhibiting mTOR signaling pathway and expression of MDR1

Li, Qiang; Xia, Xuefeng; Ji, Jie; Ma, Jianghui; Tao, Liang; Mo, Linjun; Chen, Wei

doi:10.18632/oncotarget.16834

Cited by 28 publications

(24 citation statements)

References 38 publications

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“…The overall survival prediction of muscle‐invasive bladder cancer patients after radical cystectomy could be improved by miR‐199a‐3p . In cholangiocarcinoma cells, miR‐199a‐3p enhances cisplatin sensitivity by inhibiting mTOR signalling pathway and expression of MDR1 . miR‐199a‐3p also suppresses proliferation and invasion of prostate cancer cells by targeting Smad1 .…”

Section: Discussionmentioning

confidence: 99%

Gambogic Acid Inhibits Melanoma through Regulation of miR‐199a‐3p/ZEB1 Signalling

Liang

Zhang

Qin

et al. 2018

Basic Clin Pharma Tox

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Malignant melanoma is an aggressive form of cancer which is highly resistant to chemotherapy. We have previously found that gambogic acid (GA), a kind of polyprenylated xanthone, exhibits an antitumour role in melanoma. The study was designed to investigate novel mechanisms of the antitumour effect of GA in melanoma cells and implanted nude mice. Gambogic acid significantly decreased cell viability, increased apoptosis and reduced migration and invasion in A375 cells. In addition, cisplatin-induced cytotoxicity in both A375 and A375/CDDP cells was increased by GA. The expression of miR-199a-3p was increased by GA in A375 cells and implanted tumours, and inhibition of miR-199a-3p significantly prevented GA-induced effect on cell viability, apoptosis, migration, invasion and cisplatin sensitivity in A375 cells. miR-199a-3p mimics reduced tumour weight and volume in vivo and decreased cell viability, increased apoptosis and reduced migration and invasion in vitro. miR-199a-3p expression was decreased in melanoma tissues and cells, as compared with their controls. miR-199a-3p possessed a potential binding site in the 3'-UTR of zinc finger E-box binding homeobox (ZEB1). ZEB1 expression was increased in melanoma tissues and cells, as compared with their controls. ZEB1 and miR-199a-3p expression was negatively correlated in melanoma tissues. The expression of ZEB1 was decreased by GA in A375 cells and implanted tumours, and up-regulation of ZEB1 significantly prevented GA-induced effect on cell viability, apoptosis, migration, invasion and cisplatin sensitivity. Down-regulation of ZEB1 reduced tumour weight and volume in vivo and decreased cell viability, increased apoptosis and reduced migration and invasion in vitro. We identified the important roles of miR-199a-3p and ZEB1 in melanoma and elucidated the tumour suppressor function of miR-199a-3p through inhibition of ZEB1. The results highlight the importance of miR-199a-3p-ZEB1 signalling in antitumour effect of GA in malignant melanoma and provide novel targets for the chemotherapy of melanoma.

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Section: Discussionmentioning

confidence: 99%

Gambogic Acid Inhibits Melanoma through Regulation of miR‐199a‐3p/ZEB1 Signalling

Liang

Zhang

Qin

et al. 2018

Basic Clin Pharma Tox

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“…On the other hand, Yang et al reported that the inhibition of miR-199a-3p reduced cisplatin-induced cell apoptosis and inhibited caspase-3 activity [40]. mTOR is the target gene of miR-199a [76], regulating cell survival, proliferation, migration, and apoptosis. In addition, miR-199a-3p increased TGF-β1-induced renal fibrosis via silencing of SOCS7 and STAT3 [41].…”

Section: Versatile Msc-evs-derived Mirnas Modulate Renal Injury and Hmentioning

confidence: 99%

Immunomodulatory and Regenerative Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Renal Diseases

Tsuji

Kitamura

Wada

2020

IJMS

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Mesenchymal stem cells (MSCs) have immunomodulatory and regenerative effects in many organs, including the kidney. Emerging evidence has shown that the trophic effects from MSCs are mainly mediated by the paracrine mechanism rather than the direct differentiation of MSCs into injured tissues. These secretomes from MSCs include cytokines, growth factors, chemokines and extracellular vesicles (EVs) containing microRNAs, mRNAs, and proteins. Many research studies have revealed that secretomes from MSCs have potential to ameliorate renal injury in renal disease models, including acute kidney injury and chronic kidney disease through a variety of mechanisms. These trophic mechanisms include immunomodulatory and regenerative effects. In addition, accumulating evidence has uncovered the specific factors and therapeutic mechanisms in MSC-derived EVs. In this article, we summarize the recent advances of immunomodulatory and regenerative effects of EVs from MSCs, especially focusing on the microRNAs.

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“…Breast cancer Over-expression of these miRNAs re-sensitizes the drug-resistant cells to doxorubicin [45] miR-199a-3p MTOR Cholangiocarcinoma Reconstitution of miR-199a-3p increases growth inhibition rate and apoptosis induced by cisplatin [39] miR-210-3p ABCC5 Pancreatic cancer Elevated miR-210-3p levels improve the overall cytotoxicity of gemcitabine [26] miR-218-5p PRKCE Gallbladder cancer Elevated miR-218-5p levels potentiate gemcitabine-mediated cell death and growth inhibition [38] miR-223-3p ABCB1 Hepatocellular carcinoma Down-regulation of miR-223-3p confers resistance to doxorubicin [18] miR-326 ABCC1 Hepatocellular carcinoma Over-expression of miR-326 leads to elevated cytotoxicity of doxorubicin [23] miR-328-3p ABCG2 Breast cancer Over-expression of miR-328-3p augments the sensitivity of drug-resistant cells to mitoxantrone [29] miR-491-3p ABCB1, SP3 Hepatocellular carcinoma Down-regulation of miR-491-3p decreases the sensitivity to doxorubicin and vinblastin [19] miR-495-3p ABCB1, UBE2C Ovarian cancer, Gastric cancer, Lung cancer…”

Section: Spin1mentioning

confidence: 99%

“…There is another possibility that miR-506-3p regulates ABCB1 expression by targeting the enhancer of zeste homolog 2 (EZH2), which is a possible transcription regulator of ABCB1 [36,37]. In addition, a decrease in ABCB1 expression can be mediated by miR-199a-3p and miR-218-5p via regulating mTOR and protein kinase C epsilon (PRKCE, also known as PKCε), respectively [38,39]. Since both mTOR and PKCε activate the signal transducer and activator of transcription 3 (STAT3), a transcription factor of ABCB1 [40][41][42], it is feasible that miR-199a-3p and miR-218-5p could downregulate ABCB1 levels through a common mediator.…”

Section: Introductionmentioning

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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MiR-199a-3p enhances cisplatin sensitivity of cholangiocarcinoma cells by inhibiting mTOR signaling pathway and expression of MDR1

Cited by 28 publications

References 38 publications

Gambogic Acid Inhibits Melanoma through Regulation of miR‐199a‐3p/ZEB1 Signalling

Gambogic Acid Inhibits Melanoma through Regulation of miR‐199a‐3p/ZEB1 Signalling

Immunomodulatory and Regenerative Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Renal Diseases

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

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