scholarly journals MicroRNA-221 promotes cisplatin resistance in osteosarcoma cells by targeting PPP2R2A

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Wen-chao Yu ◽  
Hui-hao Chen ◽  
Yan-yan Qu ◽  
Chun-wei Xu ◽  
Chen Yang ◽  
...  
Keyword(s):  
Cisplatin Resistance ◽  
Small Noncoding Rnas ◽  
Osteoblast Cell Line ◽  
Dismal Prognosis ◽  
Cisplatin Sensitivity ◽  
Multi Agent ◽  
Children And Young Adults ◽  
Normal Osteoblast ◽  
Chemotherapy Patients ◽  
Subunit B

Abstract Osteosarcoma (OS), the most common malignant bone tumor, is the main cause of cancer-related deaths in children and young adults. Despite the combination of surgery and multi-agent chemotherapy, patients with OS who develop resistance to chemotherapy or experience recurrence have a dismal prognosis. MicroRNAs (miRNAs) are a class of small noncoding RNAs that repress their targets by binding to the 3′-UTR and/or coding sequences, leading to the inhibition of gene expression. miR-221 is found to be up-regulated in tumors when compared with their matched normal osteoblast tissues. We also observed significant miR-221 up-regulation in the OS cell lines, MG-63, SaoS-2, and U2OS, when compared with the normal osteoblast cell line, HOb. Overexpression of miR-221 promoted OS cell invasion, migration, proliferation, and cisplatin resistance. MG-63 and SaoS-2 cells transfected with miR-221 mimics were more resistant to cisplatin. The IC50 of MG-63 cells transfected with control mimics was 1.24 μM. However, the IC50 of MG-63 cells overexpressing miR-221 increased to 7.65 μM. Similar results were found in SaoS-2 cells, where the IC50 for cisplatin increased from 3.65 to 8.73 μM. Thus, we report that miR-221 directly targets PP2A subunit B (PPP2R2A) in OS by binding to the 3′-UTR of the PPP2R2A mRNA. Restoration of PPP2R2A in miR-221-overexpressing OS cells recovers the cisplatin sensitivity of OS cells. Therefore, the present study suggests a new therapeutic approach by inhibiting miR-221 for anti-chemoresistance in OS.

scholarly journals Midazolam increases cisplatin-sensitivity in non-small cell lung cancer (NSCLC) via the miR-194-5p/HOOK3 axis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tingting Sun ◽  
Jing Chen ◽  
Xuechao Sun ◽  
Guonian Wang
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cell Apoptosis ◽  
Cisplatin Resistance ◽  
Small Cell ◽  
Luciferase Reporter ◽  
Small Cell Lung ◽  
Cisplatin Sensitivity

Abstract Backgrounds As previously reported, midazolam anesthesia exerts tumor-suppressing effects in non-small cell lung cancer (NSCLC), but the regulating effects of this drug on cisplatin-resistance in NSCLC have not been studied. Thus, we designed this study to investigate this issue and preliminarily delineate the potential molecular mechanisms. Methods We performed MTT assay and trypan blue staining assay to measure cell proliferation and viability. Cell apoptosis was examined by FCM. qRT-PCR and immunoblotting were performed to determine the expression levels of genes. The targeting sites between genes were predicted by bioinformatics analysis and were validated by dual-luciferase reporter gene system assay. Mice tumor-bearing models were established and the tumorigenesis was evaluated by measuring tumor weight and volume. Immunohistochemistry (IHC) was used to examine the pro-proliferative Ki67 protein expressions in mice tumor tissues. Results The cisplatin-resistant NSCLC (CR-NSCLC) cells were treated with high-dose cisplatin (50 μg/ml) and low-dose midazolam (10 μg/ml), and the results showed that midazolam suppressed cell proliferation and viability, and promoted cell apoptosis in cisplatin-treated CR-NSCLC cells. In addition, midazolam enhanced cisplatin-sensitivity in CR-NSCLC cell via modulating the miR-194-5p/hook microtubule-tethering protein 3 (HOOK3) axis. Specifically, midazolam upregulated miR-194-5p, but downregulated HOOK3 in the CR-NSCLC cells, and further results validated that miR-194-5p bound to the 3’ untranslated region (3’UTR) of HOOK3 mRNA for its inhibition. Also, midazolam downregulated HOOK3 in CR-NSCLC cells by upregulating miR-194-5p. Functional experiments validated that both miR-194-5p downregulation and HOOK3 upregulation abrogated the promoting effects of midazolam on cisplatin-sensitivity in CR-NSCLC cells. Conclusions Taken together, this study found that midazolam anesthesia reduced cisplatin-resistance in CR-NSCLC cells by regulating the miR-194-5p/HOOK3 axis, implying that midazolam could be used as adjuvant drug for NSCLC treatment in clinical practices.

scholarly journals Alternative redox forms of ASNA-1 separate insulin signaling from tail-anchored protein targeting and cisplatin resistance in C. elegans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Dorota Raj ◽  
Ola Billing ◽  
Agnieszka Podraza-Farhanieh ◽  
Bashar Kraish ◽  
Oskar Hemmingsson ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Insulin Secretion ◽  
Protein Targeting ◽  
Cisplatin Resistance ◽  
Acquired Resistance ◽  
Endoplasmic Reticulum Membrane ◽  
C Elegans ◽  
Cisplatin Sensitivity ◽  
Tumor Environment ◽  
The One

AbstractCisplatin is a frontline cancer therapeutic, but intrinsic or acquired resistance is common. We previously showed that cisplatin sensitivity can be achieved by inactivation of ASNA-1/TRC40 in mammalian cancer cells and in Caenorhabditis elegans. ASNA-1 has two more conserved functions: in promoting tail-anchored protein (TAP) targeting to the endoplasmic reticulum membrane and in promoting insulin secretion. However, the relation between its different functions has remained unknown. Here, we show that ASNA-1 exists in two redox states that promote TAP-targeting and insulin secretion separately. The reduced state is the one required for cisplatin resistance: an ASNA-1 point mutant, in which the protein preferentially was found in the oxidized state, was sensitive to cisplatin and defective for TAP targeting but had no insulin secretion defect. The same was true for mutants in wrb-1, which we identify as the C. elegans homolog of WRB, the ASNA1/TRC40 receptor. Finally, we uncover a previously unknown action of cisplatin induced reactive oxygen species: cisplatin induced ROS drives ASNA-1 into the oxidized form, and selectively prevents an ASNA-1-dependent TAP substrate from reaching the endoplasmic reticulum. Our work suggests that ASNA-1 acts as a redox-sensitive target for cisplatin cytotoxicity and that cisplatin resistance is likely mediated by ASNA-1-dependent TAP substrates. Treatments that promote an oxidizing tumor environment should be explored as possible means to combat cisplatin resistance.

scholarly journals CircDOCK1 promotes the tumorigenesis and cisplatin resistance of osteogenic sarcoma via the miR-339-3p/IGF1R axis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Shenglong Li ◽  
Fei Liu ◽  
Ke Zheng ◽  
Wei Wang ◽  
Enduo Qiu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cisplatin Resistance ◽  
Osteogenic Sarcoma ◽  
Mg63 Cell ◽  
Circular Rnas ◽  
Rna Immunoprecipitation ◽  
Cisplatin Sensitivity ◽  
Regulatory Effects

Abstract Background Circular RNAs (circRNAs), a class of noncoding RNAs (ncRNAs), may modulate gene expression by binding to miRNAs. Additionally, recent studies show that circRNAs participate in some pathological processes. However, there is a large gap in the knowledge about circDOCK1 expression and its biological functions in osteogenic sarcoma (OS). Methods Differentially expressed circRNAs in OS cell lines and tissues were identified by circRNA microarray analysis and quantitative real-time PCR (qRT–PCR). To explore the actions of circDOCK1 in vivo and in vitro, circDOCK1 was knocked down or overexpressed. To assess the binding and regulatory associations among miR-339-3p, circDOCK1 and IGF1R, we performed rescue experiments, RNA immunoprecipitation (RIP), RNA pulldown assays and dual-luciferase assays. Moreover, we performed apoptosis assays to reveal the regulatory effects of the circDOCK1/miR-339-3p/IGF1R axis on cisplatin sensitivity. Results CircDOCK1 expression remained stable in the cytoplasm and was higher in OS tissues and cells than in the corresponding controls. Overexpression of circDOCK1 increased oncogenicity in vivo and malignant transformation in vitro. In the U2OS and MG63 cell lines, circDOCK1 modulated tumor progression by regulating IGF1R through sponging of miR-339-3p. Additionally, in the U2OS/DDP and MG63/DDP cell lines, cisplatin sensitivity was regulated by circDOCK1 via the miR-339-3p/IGF1R axis. Conclusions CircDOCK1 can promote progression and regulate cisplatin sensitivity in OS via the miR-339-3p/IGF1R axis. Thus, the circDOCK1/miR-339-3p/IGF1R axis may be a key mechanism and therapeutic target in OS.

scholarly journals The M1 aminopeptidase NPEPPS is a novel regulator of cisplatin sensitivity

2021 ◽  
Author(s):  
Robert T. Jones ◽  
Andrew Goodspeed ◽  
Maryam C. Akbarzadeh ◽  
Mathijs Scholtes ◽  
Hedvig Vekony ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cisplatin Resistance ◽  
Treatment Resistance ◽  
Anion Channel ◽  
List Type ◽  
Cancer Models ◽  
Cisplatin Sensitivity ◽  
Cancer Types

ABSTRACTDespite routine use of platinum-based chemotherapeutics across diverse cancer types, there remains a need to improve efficacy and patient selection for treatment. A multi-omic assessment of five human bladder cancer cell lines and their chemotherapy resistant derivatives, coupled with whole-genome CRISPR screens were used to identify puromycin- sensitive aminopeptidase, NPEPPS, as a novel functional driver of treatment resistance to cisplatin. Depletion of NPEPPS resulted in enhanced cellular cisplatin import, sensitization of resistant cancer cells to cisplatin in vitro and in vivo. Pharmacologic inhibition of NPEPPS with tosedostat in cells and in chemoresistant, patient-derived tumor organoids improved response to cisplatin. Depletion of LRRC8A and LRRC8D, two subunits of the volume regulated anion channel (VRAC), a known importer of intracellular cisplatin, enhanced resistance to cisplatin. Linking NPEPPS function to VRAC cisplatin import supports NPEPPS as a driver of cisplatin resistance and by virtue of clinically available inhibitors, the potential for rapid clinical translation.HIGHLIGHTS∙CRISPR screens with multi-omics identify NPEPPS as a driver of cisplatin resistance∙NPEPPS depletion in multiple bladder cancer models enhances cisplatin sensitivity∙LRRC8A and LRRC8D loss increase resistance to cisplatin in CRISPR screens∙Unique resource of functional and multi-omic data is provided to the community

scholarly journals CircRNA-DOPEY2 enhances the chemosensitivity of esophageal cancer cells by inhibiting CPEB4-mediated Mcl-1 translation

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Zhenchuan Liu ◽  
Shaorui Gu ◽  
Kaiqin Wu ◽  
Lei Li ◽  
Chenglai Dong ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Cisplatin Resistance ◽  
Critical Role ◽  
Circular Rnas ◽  
Major Barrier ◽  
Downstream Target ◽  
Cisplatin Sensitivity

Abstract Background Cisplatin-based chemotherapy is a mainstay systematic therapy for advanced esophageal squamous cell carcinoma (ESCC), and cisplatin resistance, which is not uncommon, is the major barrier to improving patient outcomes. Circular RNAs (circRNAs) are novel noncoding RNAs that are implicated in cancer progression, but their involvement in modulating cisplatin responsiveness in ESCC remains unknown. Methods Bioinformatics analysis was used to profile and identify the circRNAs involved in cisplatin responsiveness in ESCC. The chemosensitive role of cDOPEY2 was confirmed both in vitro and in vivo. The molecular mechanism of cDOPEY2 was investigated by mass spectrometry, immunoprecipitation, and ubiquitination analyses. Results We report that a novel circRNA (cDOPYE2, hsa_circ_0008078) was markedly downregulated in cisplatin-resistant ESCC cells (ESCC-CR) compared with parental chemosensitive cells. Re-expression of cDOPEY2 substantially enhanced the cell-killing ability of cisplatin by augmenting the apoptotic process in ESCC-CR cells, which was achieved by decreasing the abundance of the antiapoptotic protein Mcl-1. Mechanistically, we showed that cDOPEY2 acted as a protein scaffold to enhance the interaction between the cytoplasmic polyadenylation element binding protein (CPEB4) and the E3 ligase TRIM25, which in turn facilitated the ubiquitination and degradation of CPEB4. The increased Mcl-1 expression in ESCC-CR cells was dependent on the binding of CPEB4 to its untranslated mRNA, and depletion of CPEB4 mediated by cDOPEY2 reversed this effect. Rescue experiments confirmed that the critical role of cDOPEY2 in maintaining cisplatin sensitivity was dependent on the depletion of CEPB4 and its downstream target Mcl-1. Clinical and in vivo data further corroborated the significant relevance of cDOPEY2 to cisplatin responsiveness in ESCC. Conclusions We provide evidence that cDOPEY2 inhibits CPEB4-mediated Mcl-1 translation by promoting the ubiquitination and degradation of CPEB4 to alleviate cisplatin resistance, indicating that cDOPEY2 may serve as a valuable biomarker and potential therapeutic target in ESCC.

scholarly journals Low GAS5 expression may predict poor survival and cisplatin resistance in cervical cancer

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Xingyu Fang ◽  
Guanglei Zhong ◽  
Yuhan Wang ◽  
Zhongqiu Lin ◽  
Rongchun Lin ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Animal Studies ◽  
Cisplatin Resistance ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Luciferase Reporter ◽  
Poor Overall Survival ◽  
Cisplatin Sensitivity

Abstract Cisplatin resistance is a major challenge in cervical cancer (CC) chemotherapy. Growth arrest‐specific 5 (GAS5) has been reported to be a tumour suppressor gene in CC. However, the mechanism of GAS5 in chemoresistance remains undetermined. Our research evaluated GAS5 expression in normal and CC tissues by qPCR and in situ hybridization (ISH). Statistical analysis was conducted to analyse the association of GAS5 expression with survival. Biochemical methods were used to screen upstream and downstream regulators of GAS5. Then, interactions were confirmed by ChIP, RNA pull-down, RNA immunoprecipitation (RIP), dual-luciferase reporter and real-time PCR assays. The cisplatin sensitivity of GAS5-overexpressing CC cells was demonstrated in vitro and in vivo. The results showed that low GAS5 expression was correlated with poor overall survival. Mechanistically, GAS5 was transcriptionally modulated by P-STAT3 and served as a competing endogenous RNA (ceRNA) of miR-21 to indirectly affect cisplatin sensitivity through PDCD4 regulation in CC cells. Animal studies confirmed that GAS5 enhanced cisplatin sensitivity and promoted PDCD4 expression in vivo. GAS5 was regulated by P-STAT3 and affected the sensitivity of CC to cisplatin-based chemotherapy through the miR-21/PDCD4 axis. This result may provide new insight into cisplatin-based therapy.

scholarly journals Expression of the chrXq27.3 miRNA cluster in recurrent ovarian clear cell carcinoma and its impact on cisplatin resistance

Oncogene ◽  
2021 ◽  
Author(s):  
Kosuke Yoshida ◽  
Akira Yokoi ◽  
Mai Sugiyama ◽  
Shingo Oda ◽  
Kazuhisa Kitami ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Cisplatin Resistance ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Critical Role ◽  
Molecular Characteristics ◽  
Mirna Cluster ◽  
Ovarian Clear Cell Carcinoma ◽  
Dismal Prognosis ◽  
Cancer Tissues

AbstractOvarian clear cell carcinoma (OCCC) is a histological subtype of epithelial ovarian cancer and exhibits dismal prognosis due to chemoresistance. Moreover, only few effective therapeutic options exist for patients with recurrent OCCC, and an understanding of its molecular characteristics is essential for the development of novel therapeutic approaches. In the present study, we investigated unique MicroRNAs (miRNA) profiles in recurrent/metastatic OCCC and the role of miRNAs in cisplatin resistance. Comprehensive miRNA sequencing revealed that expression of several miRNAs, including miR-508-3p, miR-509-3p, miR-509-3-5p, and miR-514a-3p was remarkably less in recurrent cancer tissues when compared with that in paired primary cancer tissues. These miRNAs are located in the chrXq27.3 region on the genome. Moreover, its expression was negative in omental metastases in two patients with advanced OCCC. In vitro analyses revealed that overexpression of miR-509-3p and miR-509-3-5p reversed cisplatin resistance and yes-associated protein 1 (YAP1) was partially responsible for the resistance. Immunohistochemistry revealed that YAP1 expression was inversely correlated with the chrXq27.3 miRNA cluster expression. In conclusion, these findings suggest that alteration of the chrXq27.3 miRNA cluster could play a critical role in chemoresistance and miRNAs in the cluster and their target genes can be potential therapeutic targets.

scholarly journals Deregulation of Exo70 Facilitates Innate and Acquired Cisplatin Resistance in Epithelial Ovarian Cancer by Promoting Cisplatin Efflux

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3467
Author(s):  
Yujie Zhao ◽  
Xiaoting Hong ◽  
Xiong Chen ◽  
Chun Hu ◽  
Weihong Lu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cisplatin Resistance ◽  
Progression Free Survival ◽  
Platinum Resistance ◽  
Lysosomal Degradation ◽  
Free Survival ◽  
Cisplatin Sensitivity

Whilst researches elucidating a diversity of intracellular mechanisms, platinum-resistant epithelial ovarian cancer (EOC) remains a major challenge in the treatment of ovarian cancer. Here we report that Exo70, a key subunit of the exocyst complex, contributes to both innate and acquired cisplatin resistance of EOC. Upregulation of Exo70 is observed in EOC tissues and is related to platinum resistance and progression-free survival of EOC patients. Exo70 suppressed the cisplatin sensitivity of EOC cells through promoting exocytosis-mediated efflux of cisplatin. Moreover, cisplatin-induced autophagy-lysosomal degradation of Exo70 protein by modulating phosphorylation of AMPK and mTOR, thereby reducing the cellular resistance. However, the function was hampered during prolonged cisplatin treatment, which in turn stabilized Exo70 to facilitate the acquired cisplatin resistance of EOC cells. Knockdown of Exo70, or inhibiting exocytosis by Exo70 inhibitor Endosidin2, reversed the cisplatin resistance of EOC cells both in vitro and in vivo. Our results suggest that Exo70 overexpression and excessive stability contribute to innate and acquired cisplatin resistance through the increase in cisplatin efflux, and targeting Exo70 might be an approach to overcome cisplatin resistance in EOC treatment.

scholarly journals New Synthetic Lethality Re-Sensitizing Platinum-Refractory Cancer Cells to Cisplatin In Vitro: The Rationale to Co-Use PARP and ATM Inhibitors

2021 ◽  
Vol 22 (24) ◽  
pp. 13324
Author(s):  
Watson P. Folk ◽  
Alpana Kumari ◽  
Tetsushi Iwasaki ◽  
Erica K. Cassimere ◽  
Slovénie Pyndiah ◽  
...  
Keyword(s):  
Tumor Suppressor ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Synthetic Lethality ◽  
Lethal Effect ◽  
Parp Inhibition ◽  
Synthetic Lethal ◽  
Cisplatin Sensitivity ◽  
Platinum Refractory

The pro-apoptotic tumor suppressor BIN1 inhibits the activities of the neoplastic transcription factor MYC, poly (ADP-ribose) polymerase-1 (PARP1), and ATM Ser/Thr kinase (ATM) by separate mechanisms. Although BIN1 deficits increase cancer-cell resistance to DNA-damaging chemotherapeutics, such as cisplatin, it is not fully understood when BIN1 deficiency occurs and how it provokes cisplatin resistance. Here, we report that the coordinated actions of MYC, PARP1, and ATM assist cancer cells in acquiring cisplatin resistance by BIN1 deficits. Forced BIN1 depletion compromised cisplatin sensitivity irrespective of Ser15-phosphorylated, pro-apoptotic TP53 tumor suppressor. The BIN1 deficit facilitated ATM to phosphorylate the DNA-damage-response (DDR) effectors, including MDC1. Consequently, another DDR protein, RNF8, bound to ATM-phosphorylated MDC1 and protected MDC1 from caspase-3-dependent proteolytic cleavage to hinder cisplatin sensitivity. Of note, long-term and repeated exposure to cisplatin naturally recapitulated the BIN1 loss and accompanying RNF8-dependent cisplatin resistance. Simultaneously, endogenous MYC was remarkably activated by PARP1, thereby repressing the BIN1 promoter, whereas PARP inhibition abolished the hyperactivated MYC-dependent BIN1 suppression and restored cisplatin sensitivity. Since the BIN1 gene rarely mutates in human cancers, our results suggest that simultaneous inhibition of PARP1 and ATM provokes a new BRCAness-independent synthetic lethal effect and ultimately re-establishes cisplatin sensitivity even in platinum-refractory cancer cells.

scholarly journals MiR-34c Downregulation Leads to SOX4 Overexpression and Cisplatin Resistance in Nasopharyngeal Carcinoma

2020 ◽  
Author(s):  
Pierre-Antoine Bissey ◽  
Mona Teng ◽  
Jacqueline H Law ◽  
Wei Shi ◽  
Jeff P Bruce ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Epithelial To Mesenchymal Transition ◽  
Cisplatin Resistance ◽  
Chemotherapy Resistance ◽  
Loss Of Function ◽  
Mesenchymal Transition ◽  
Over Expression ◽  
Tgfβ Receptor ◽  
Cisplatin Sensitivity

Abstract Background : A major cause of disease-related death in nasopharyngeal carcinoma (NPC) is the development of distant metastasis (DM) despite combination chemoradiotherapy treatment. We previously identified and validated a four microRNA (miRNA) signature that is prognostic for DM. In this study, characterization of a key component of this signature, miR-34c, revealed its role in chemotherapy resistance. Methods: 246 NPC patient biopsy samples were subject to comprehensive miRNA profiling and immunohistochemistry (IHC). Two human normal nasopharyngeal cell lines (immortalized; NP69 and NP460), as well as the NPC cell line C666-1, were used to generate pre-miR-34c (gain-of-function) and anti-miR-34c (loss-of-function) cells. Signaling pathways were assessed using quantitative real-time PCR (qRT-PCR) and Western blot. Cell viability was measured using the ATPlite assay. Results: MiR-34c was downregulated in NPC patient samples, and confirmed in vitro to directly target SOX4, a master regulator of epithelial-to-mesenchymal transition (EMT). MiR-34c downregulation triggered EMT-representative changes in NP69 and NP460 whereby Snail, ZEB1, CDH2, and SOX2 were upregulated, while Claudin-1 and CDH1 were downregulated. Phenotypically, inhibition of miR-34c led to cisplatin resistance, whereas miR-34c over-expression sensitized NPC cells to cisplatin. TGFβ1 decreased miR-34c and increased SOX4 expression in vitro . The TGFβ receptor 1 inhibitor SB431542 reduced SOX4 expression and increased cisplatin sensitivity. Finally, IHC revealed that lower SOX4 expression was associated with improved overall survival in chemotherapy-treated NPC patients. Conclusion: miR-34c downregulation correlates with higher incidence of DM. Repression of miR-34c was shown to increase SOX4 expression, which leads to cisplatin resistance, while TGFβ1 was found to repress miR-34c expression. Taken together, our study demonstrates that inhibition of the TGFβ1 pathway could be a strategy to restore cisplatin sensitivity in NPC.

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