MiR-205 and miR-218 expression is associated with carboplatin chemoresistance and regulation of apoptosis via Mcl-1 and Survivin in lung cancer cells

Zarogoulidis, Paul; Petanidis, Savvas; Kioseoglou, Efrosini; Domvri, Kalliopi; Anestakis, Doxakis; Zarogoulidis, Konstantinos

doi:10.1016/j.cellsig.2015.04.009

Cited by 66 publications

(48 citation statements)

References 49 publications

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“…49 miR-205 also enhances cisplatin toxicity in castration-resistant prostate cancer cells by targeting RAB27A and LAMP3, 50 whereas in lung cancer, miR-205 overexpression is associated with carboplatin insensitivity by altering the expression of apoptosis-related genes. 51 However, the effect of miR-205 in breast cancer chemoresistance is still poorly understood. Here, using chemoresistant breast cancer cell models, we show that miR-205 targets VEGFA as well as FGF2 mRNA 3′-UTR and represses their expression, leading to impaired PI3K/AKT signaling and increased apoptosis both in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 99%

miRNA-205 targets VEGFA and FGF2 and regulates resistance to chemotherapeutics in breast cancer

et al. 2016

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MicroRNAs (miRNAs) have critical roles in regulating cancer cell survival, proliferation and sensitivity to chemotherapy. The potential application of using miRNAs to predict chemotherapeutic response to cancer treatment is highly promising. However, the underlying mechanisms of chemotherapy response control by miRNAs remain to be fully identified and their prognostic value has not been fully evaluated. Here we show a strong correlation between miR-205 expression and chemosensitivtiy to TAC (docetaxol, doxorubicin plus cyclophosphamide), a widely-used neoadjuvant chemotherapy (NAC) regimen, for breast cancer patients. High level of miR-205 predicted better response to TAC regimen NAC in breast cancer patients. We found miR-205 downregulated in both MCF-7/A02 and CALDOX cells, two drug-resistant derivatives of MCF-7 and Cal51 cells, and its ectopic expression led to an increase in apoptosis resensitization of both drug-resistant cell lines to doxorubicin and taxol. We further show that miR-205 directly binds VEGFA and FGF2 mRNA 3′-UTRs and confirm that miR-205 levels are negatively correlated with VEGFA and FGF2 mRNA expression in breast cancer patients. Adding VEGFA and FGF2 exogenously to chemosensitive breast cancer cells and chemoresistant cells with miR-205 overexpression led to drug resistance. Consistently, low VEGFA and FGF2 expression correlated with better response to NAC in breast cancer patients. In addition, inhibition of tumor growth and resensitization to doxorubicin were also observed in mouse tumor xenografts from cells overexpressing miR-205. Taken together, our data suggest that miR-205 enhances chemosensitivity of breast cancer cells to TAC chemotherapy by suppressing both VEGFA and FGF2, leading to evasion of apoptosis. MiR-205 may serve as a predictive biomarker and a potential therapeutic target in breast cancer treatment.

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Section: Discussionmentioning

confidence: 99%

miRNA-205 targets VEGFA and FGF2 and regulates resistance to chemotherapeutics in breast cancer

et al. 2016

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“…MiR-218 functions as a tumour suppressor by targeting BMI-1, survivin or HMGB1 in different types of cancers. Moreover, miR-218 has been found to regulate chemosensitivity in lung cancer[30] , pancreatic cancer[26] and overexpression of miR-218 could induce apoptosis and increase sensitivity to chemotherapeutics in breast cancer by targeting surviving [32]. In our previous study, we found that miR-218 was significantly down-regulated in bladder cancer tissues and that miR-218 could inhibit bladder cancer cell proliferation, migration and invasion by targeting BMI-1 [14].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1

Yang

Cheng

Zhang

et al. 2017

Cell Physiol Biochem

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Background/Aims: MicroRNA-218 (miR-218) is down-regulated in many malignancies that have been implicated in the regulation of diverse processes in cancer cells. However, the involvement of miR-218 in chemo-sensitivity to cisplatin and the precise mechanism of this action remained unknown in bladder cancer. Methods: qRT-PCR was used to detect miR-218 and its target Glut1 expression in bladder cancer cell lines T24 and EJ. CCK-8 method was utilized to measure the cell viability. IC 50 was calculated via a probit regression model. Glut1 was detected by western blotting for analysis of potential mechanism. Luciferase reporter assay was utilized to validate Glut1 as a direct target gene of miR-218. The intracellular level of GSH and ROS were determined using a commercial colorimetric assay kit and 2’, 7’-dichlorodihydro-fluorescein diacetate, respectively. Results: Over-expression of miR-218 significantly reduced the rate of glucose uptake and total level of GSH and enhanced the chemo-sensitivity of bladder cancer to cisplatin. Mechanistically, Glut1 was found to be a direct and functional target of miR-218. Up-regulation of Glut1 could restore chemo-resistance in T24 and EJ cells. On the contrary, knockdown of Glut1 could generate a similar effect as up-regulating the expression of miR-218. Conclusions: MiR-218 increases the sensitivity of bladder cancer to cisplatin by targeting Glut1. Restoration of miR-218 and repression of glut1 may provide a potential strategy to restore chemo-sensitivity in bladder cancer.

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“…In BC, it acts as a risk factor in ductal carcinoma in situ (DCIS) (205). In association with platinum compounds, miR-218 and miR-205 inhibit tumorigenesis and overcome chemoresistance in lung cancer (206). In prostate cancer, miR-218 up-regulation inhibited tumor growth and increased chemo-sensitivity to cisplatin, by negatively regulating BCAT1 (207).…”

Section: A Network Analysis: the Most Central Ncrnas In Chemoresistancementioning

confidence: 99%

“…In our review, the role of miR-205, which regulates EMT (351), emerged as one of such cases. It is apparent that miR-205 upregulation causes inhibition of chemoresistance to gemcitabine in pancreatic cancer (352), but Zarogoulidis et al demonstrated that miR-205 and miR-218 were associated with carboplatin resistance in lung cancer (206). miR-181b over-expression increased gemcitabine resistance (353), whereas miR-181b was involved in temozolomide sensitivity in glioma by targeting MEK1 (354).…”

Section: Drugs/non-coding Rnas Subnetworkmentioning

confidence: 99%

The Network of Non-coding RNAs in Cancer Drug Resistance

et al. 2018

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Non-coding RNAs (ncRNAs) have been implicated in most cellular functions. The disruption of their function through somatic mutations, genomic imprinting, transcriptional and post-transcriptional regulation, plays an ever-increasing role in cancer development. ncRNAs, including notorious microRNAs, have been thus proposed to function as tumor suppressors or oncogenes, often in a context-dependent fashion. In parallel, ncRNAs with altered expression in cancer have been reported to exert a key role in determining drug sensitivity or restoring drug responsiveness in resistant cells. Acquisition of resistance to anti-cancer drugs is a major hindrance to effective chemotherapy and is one of the most important causes of relapse and mortality in cancer patients. For these reasons, non-coding RNAs have become recent focuses as prognostic agents and modifiers of chemo-sensitivity. This review starts with a brief outline of the role of most studied non-coding RNAs in cancer and then highlights the modulation of cancer drug resistance via known ncRNAs based mechanisms. We identified from literature 388 ncRNA-drugs interactions and analyzed them using an unsupervised approach. Essentially, we performed a network analysis of the non-coding RNAs with direct relations with cancer drugs. Within such a machine-learning framework we detected the most representative ncRNAs-drug associations and groups. We finally discussed the higher integration of the drug-ncRNA clusters with the goal of disentangling effectors from downstream effects and further clarify the involvement of ncRNAs in the cellular mechanisms underlying resistance to cancer treatments.

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MiR-205 and miR-218 expression is associated with carboplatin chemoresistance and regulation of apoptosis via Mcl-1 and Survivin in lung cancer cells

Cited by 66 publications

References 49 publications

miRNA-205 targets VEGFA and FGF2 and regulates resistance to chemotherapeutics in breast cancer

miRNA-205 targets VEGFA and FGF2 and regulates resistance to chemotherapeutics in breast cancer

MicroRNA-218 Increases the Sensitivity of Bladder Cancer to Cisplatin by Targeting Glut1

The Network of Non-coding RNAs in Cancer Drug Resistance

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