scholarly journals WT1 Enhances Proliferation and Impedes Apoptosis in KRAS Mutant NSCLC via Targeting cMyc

2015 ◽  
Vol 35 (2) ◽  
pp. 647-662 ◽  
Author(s):  
Chen Wu ◽  
Sihan Wang ◽  
Caihua Xu ◽  
Andreas Tyler ◽  
Xingru Li ◽  
...  
Keyword(s):  
Negative Impact ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Wild Type ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Proliferation And Apoptosis ◽  
Mutant Cells ◽  
Dual Luciferase Reporter Assay

Background: A novel link between oncogenic KRAS signalling and WT1 was recently identified. We sought to investigate the role of WT1 and KRAS in proliferation and apoptosis. Methods: KRAS mutations and WT1 (cMyc) expression were detected using Sanger sequencing and real-time PCR in 77 patients with non-small cell lung cancer (NSCLC). Overexpression and knockdown of WT1 were generated with plasmid and siRNA via transient transfection technology in H1299 and H1568 cells. MTT assay for detection of cell proliferation, and TUNEL assay and proteomic profiler assay for apoptosis evaluation were carried out. Dual luciferase reporter assay and ChIP-PCR were performed to validate the effect of WT1 on the cMyc promoter. Results: KRAS mutations showed a negative impact on overall survival (OS). High expressions of WT1 and cMyc were associated with poor OS in KRAS mutant subgroup. The potential mechanisms that WT1 promotes proliferation and impedes apoptosis through affecting multiple apoptosis-related regulators in KRAS mutant NSCLC cells were identified. WT1 could activate cMyc promoter directly in KRAS mutant cells. Conclusion: The results suggest that WT1 and c-MYC expression is important for survival in KRAS mutant tumors as opposed to KRAS wild-type tumors. For treatment of KRAS mutant NSCLC, targeting WT1 and cMyc may provide alternative therapeutic strategies.

scholarly journals Knockdown of LincRNA PADNA Promotes Bupivacaine-Induced Neurotoxicity by miR-194/FBXW7 Axis

2020 ◽  
Author(s):  
Fan Yuning ◽  
Chen Liang ◽  
Wang Tenghuan ◽  
Nan Zhenhua ◽  
Shengkai Gong
Keyword(s):  
Functional Analysis ◽  
Western Blot ◽  
Cell Viability ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Drg Neurons ◽  
Dual Luciferase Reporter Assay

Abstract The aim of the study was to explore the function and mechanism of lincRNA PADNA in bupivacaine-induced neurotoxicity. Mouse DRG neurons were cultured in vitro and treated with bupivacaine to establish the neurotoxicity model. Caspase3 activity, cell viability, tunel assay were analyzed to assess the role of lincRNA PADNA. Dual-luciferase reporter assay was used to determine the binding target of lincRNA PANDA. The expression of lincRNA PADNA was significantly increased with the increasing concentration of bupivacaine. Functional analysis revealed that knockdown of lincRNA PADNA accelerated the caspase3 activity and inhibited the cell viability. Western blot showed that knockdown of lincRNA PADNA promoted the occurrence of cleaved-caspase3. We also proved that lincRNA PADNA may bind with miR-194. Overexpression of miR-194 could rescued the function of lincRNA PADNA, suggesting that lincRNA PADNA may sponge miR-194. In addition, we provided new evidences that lincRNA PADNA/miR-194/FBXW7 axis play an important role in the neurotoxicity process. We performed comprehensive experiments to verify the function and mechanism of lincRNA PADNA in bupivacaine-induced neurotoxicity. Our study provided new evidences and clues for prevention of neurotoxicity.

scholarly journals Circular RNA SIPA1L1 Promotes Osteogenesis via Regulating the MIR-617/SMAD3 Axis in Dental Pulp Stem Cells

2020 ◽  
Author(s):  
Xingyun Ge ◽  
Zehan Li ◽  
Zhou Zhou ◽  
Yibo Xia ◽  
Minxia Bian ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Regeneration ◽  
Dental Pulp ◽  
Sanger Sequencing ◽  
Inhibitory Effect ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Dual Luciferase Reporter Assay

Abstract Background: Bone regeneration is preferred for bone loss caused by tumors, bone defects, fractures, etc. Recently, mesenchymal stem cells are considered as optimistic tools for bone defect therapy. Dental pulp stem cells (DPSCs) are a promising candidate for regenerative medicine and bone regeneration. Our previous study showed that up-regulated circSIPA1L1 during osteogenesis of DPSCs is of significance. In this paper, the potential role of circSIPA1L1 in osteogenesis of DPSCs and its underlying mechanisms are explored.Methods: The circular structure of circSIPA1L1 was identified by Sanger sequencing and PCR. Regulatory effects of circSIPA1L1 and miR-617 on mineral deposition in DPSCs were assessed by alkaline phosphatase (ALP) and alizarin red S (ARS) staining and in vivo bone formation assay were conducted to verify the biological influences of circSIPA1L1 on DPSCs. Western blot was performed to detect the protein expression of Smad3. Localization of circSIPA1L1 and miR-617 was confirmed by FISH. Dual-luciferase reporter assay and rescue experiments were conducted to investigate the role of the circSIPA1L1/miR-617/Smad3 regulatory axis in osteogenesis of DPSCs.Results: Sanger sequencing and back-to-back primer experiments confirmed the closed loop structure of circSIPA1L1. CircSIPA1L1 could promote the committed differentiation of DPSCs. MiR-617 was predicted to be the target binding circSIPA1L1 through MiRDB, miRTarBase, and TargetScan database analyses, which was further confirmed by dual-luciferase reporter assay. FISH results showed that circSIPA1L1 and miR-617 colocalize in the cytoplasm of DPSCs. MiR-617 exerted an inhibitory effect on osteogenesis of DPSCs. Knockdown of circSIPA1L1 or upregulation of miR-617 down-regulated phosphorylated Smad3. In addition, rescue experiments showed that knockdown of miR-617 reversed the inhibitory effect of circSIPA1L1 on osteogenesis of DPSCs.Conclusion: CircRNASIPA1L1 promotes osteogenesis of DPSCs by adsorbing miR-617 and further targeting Smad3.

MiR-877-5p down-regulation of PDK-1 involving in aspirin-induced gastric epithelial cells damage

2020 ◽  
Author(s):  
zongdan jiang ◽  
Ran Dan ◽  
Zou Jianjun ◽  
Wang Zhibing ◽  
Wang Zhi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Target Gene ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Gastric Epithelial Cells ◽  
Reporter Assay ◽  
Qrt Pcr ◽  
Proliferation And Apoptosis ◽  
Mucosal Erosion ◽  
Dual Luciferase Reporter Assay

Abstract It has been found that the expression of miR-877-5p is increased in serum of patients taking NSAIDs drugs. However, whether miR-877-5p play a role in aspirin-induced gastrointestinal mucosal erosion remains largely unknown. In this study, we investigated the effects of miR-877-5p on gastric epithelial cells (GES-1) proliferation and apoptosis in vitro. MiR-877-5p mimic/inhibitor and their oligonucleotides were transfected into GES-1 cells, then GES-1 cells were treated with different concentrations of aspirin (1.25, 2.5, 5 and 10 mmol/L). The bioinformatics software and dual-luciferase reporter assay were used to predict and verify the target gene of miR-877-5p. qRT-PCR and Western Blotting were employed to assess gene and protein expression, and CCK-8 assay and flow cytometry analysis were used to detect cell proliferation and apoptosis, respectively. qRT-PCR data showed that miR-877-5p level was significantly increased in aspirin incubated GES-1 cells. The proliferation of GES-1 cells were markedly inhibited and apoptosis was significantly induced in the miR-877-5p mimic groups compared to control groups. Using PITA, Targetscan and miRWalk database, the three databases indicated that PDK1 was a target gene of miR-miR-877-5p. Dual luciferase reporter assay confirmed that the existence of a direct interaction between miR-877-5p and PDK1 mRNA. Importantly, miR-877-5p knockdown resulted in a significant upregulation of PDK1 mRNA and its encoded protein in GES-1 cells. miR-877-5p plays a role in aspirin-induced gastrointestinal mucosal erosion, which may via down-regulation of targeting PDK1 gene.

scholarly journals CircRNA_100290 Promotes GC Cell Proliferation And Invasion Via miR-29b-3p/ITGA11 Axis And Is Regulated By EIF4A3

2021 ◽  
Author(s):  
Gang Wang ◽  
Dan Sun ◽  
Wenhui Li ◽  
Yan Xin
Keyword(s):  
Cell Proliferation ◽  
Western Blot ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Reporter Assay ◽  
Qrt Pcr ◽  
Node Metastasis ◽  
Dual Luciferase Reporter Assay

Abstract Background: Circular RNA (circRNA) has been reported as an important regulator in the development and progression of various carcinomas. However, the role of circRNA_100290 in gastric cancer (GC) is still unclear. This study aimed to investigate the role of circRNA_100290 in GC invasion and metastasis and its possible mechanism.Methods: The expression of circRNA_100290 in GC cells and tissues were examined using quantitative real-time polymerase chain reaction (qRT-PCR). The role of circRNA_100290 in cell proliferation, migration, and invasion was evaluated on AGS and HGC-27 cell lines in vitro. Bioinformatics tools, dual-luciferase reporter assay, Western blot assay and qRT-PCR were used to explore the downstream pathways of circRNA_100290. The mechanism underlying the regulation of the expression of circRNA_100290 was explored using RNA immunoprecipitation, qRT-PCR, and Western blot assays.Results: The expression of circRNA_100290 was found significantly upregulated in GC cells and 102 GC tissues, high expression of circRNA_100290 in GC was closely related to Borrmann’s types, lymph node metastasis and tumor-node-metastasis staging. In vitro, knockdown of circRNA_100290 in AGS and HGC-27 cells significantly inhibited cell proliferation, migration, and invasion. Mechanistically, dual-luciferase reporter assay confirmed a direct binding between circRNA_100290 and miR-29b-3p, which targets ITGA11, an oncogene which is closely related to epithelial–mesenchymal transition (EMT). In addition, EIF4A3, one of RNA binding proteins (RBPs), could inhibit the formation of circRNA_100290 via enriching flanking sites of circRNA_100290. Low expression of EIF4A3 in GC was related to a worse prognosis.Conclusions: Elevated circRNA_100290 in GC promotes cell proliferation, invasion and EMT via miR-29b-3p/ITGA11 axi and might be regulated by EIF4A3. CircRNA_100290 might be a promising biomarker and target for GC therapy.

scholarly journals Circular RNA SIPA1L1 promotes osteogenesis via regulating the miR-617/Smad3 axis in dental pulp stem cells

2020 ◽  
Author(s):  
Xingyun Ge ◽  
Zehan Li ◽  
Zhou Zhou ◽  
Yibo Xia ◽  
Minxia Bian ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Regeneration ◽  
Dental Pulp ◽  
Sanger Sequencing ◽  
Inhibitory Effect ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Dual Luciferase Reporter Assay

Abstract Background: Bone regeneration is preferred for bone loss caused by tumors, bone defects, fractures, etc. Recently, mesenchymal stem cells are considered as optimistic tools for bone defect therapy. Dental pulp stem cells (DPSCs) are a promising candidate for regenerative medicine and bone regeneration. Our previous study showed that up-regulated circSIPA1L1 during osteogenesis of DPSCs is of significance. In this paper, the potential role of circSIPA1L1 in osteogenesis of DPSCs and its underlying mechanisms are explored.Methods: The circular structure of circSIPA1L1 was identified by Sanger sequencing and PCR. Regulatory effects of circSIPA1L1 and miR-617 on mineral deposition in DPSCs were assessed by alkaline phosphatase (ALP) and alizarin red S (ARS) staining and in vivo bone formation assay were conducted to verify the biological influences of circSIPA1L1 on DPSCs. Western blot was performed to detect the protein expression of Smad3. Localization of circSIPA1L1 and miR-617 was confirmed by FISH. Dual-luciferase reporter assay and rescue experiments were conducted to investigate the role of the circSIPA1L1/miR-617/Smad3 regulatory axis in osteogenesis of DPSCs.Results: Sanger sequencing and back-to-back primer experiments confirmed the closed loop structure of circSIPA1L1. CircSIPA1L1 could promote the committed differentiation of DPSCs. MiR-617 was predicted to be the target binding circSIPA1L1 through MiRDB, miRTarBase, and TargetScan database analyses, which was further confirmed by dual-luciferase reporter assay. FISH results showed that circSIPA1L1 and miR-617 colocalize in the cytoplasm of DPSCs. MiR-617 exerted an inhibitory effect on osteogenesis of DPSCs. Knockdown of circSIPA1L1 or upregulation of miR-617 down-regulated phosphorylated Smad3. In addition, rescue experiments showed that knockdown of miR-617 reversed the inhibitory effect of circSIPA1L1 on osteogenesis of DPSCs.Conclusion: CircRNASIPA1L1 promotes osteogenesis of DPSCs by adsorbing miR-617 and further targeting Smad3.

scholarly journals miR-454 suppresses the proliferation and invasion of ovarian cancer by targeting E2F6

2020 ◽  
Author(s):  
Yunhe An ◽  
Jun Zhang ◽  
Yanjie Tian ◽  
Baoming Li ◽  
Xiaoyan Cheng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Luciferase Reporter ◽  
Ovarian Cancer Cells ◽  
Reporter Assay ◽  
Cancer Tissues ◽  
Dual Luciferase Reporter Assay

Abstract Background The aberrant expression of microRNA-454 (miR-454) has been confirmed to be involved in the development of cancers. However, the functional role of miR-454 in the progression of ovarian cancer remains unclear. Methods The expression of miR-454 in ovarian cancer cells and serum of ovarian cancer patients was detected by RT-PCR. CCK8, colony formation, transwell, and flow cytometry assays were conducted to assess the effects of miR-454 on ovarian cancer cell proliferation, migration, invasion, and apoptosis, respectively. Dual-luciferase reporter assay was used to confirm the targeting relationship between miR-454 and E2F6. The expression pattern of E2F6 in ovarian cancer tissues was detected using immunohistochemistry (IHC) assay. The relative expression of related proteins was examined using western blot analysis. Results miR-454 was markedly down-regulated by hypoxia in ovarian cancer cells. Compared with normal samples, the expression of miR-454 was up-regulated in the serum of ovarian cancer patients, and correlated with the clinicopathological stages of ovarian cancer. Next, we found that miR-454 overexpression inhibited the proliferation, migration and invasion of OVCAR3 and SKOV3 cells, as well as promoted apoptosis. In addition, the Akt/mTOR and Wnt/β-catenin signaling pathway were inhibited by miR-454 in ovarian cancer cells. Mechanically, bioinformatic analysis and dual-luciferase reporter assay confirmed that E2F6 was a direct target of miR-454 and negatively regulated by miR-454 in ovarian cancer cells. Moreover, IHC analysis showed that E2F6 was highly expressed in ovarian cancer tissues. Finally, we found that the increasing cell proliferation and migration triggered by E2F6 overexpression were abolished by miR-454 overexpression. Conclusion Taken together, these results highlight the role of miR-454 as a tumor suppressor in ovarian cancer cells by targeting E2F6, indicating that miR-454 may be a potential diagnostic biomarker and therapeutic target for ovarian cancer.

Role of miR-27a in the regulation of cellular function via the inhibition of MAP2K4 in patients with asthma

2021 ◽  
pp. 096032712110267
Author(s):  
W Yang ◽  
Z Wang ◽  
L Luo ◽  
P Yang ◽  
D Sun ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Luciferase Reporter Assay ◽  
Mitogen Activated Protein Kinase ◽  
Biological Behavior ◽  
Luciferase Reporter ◽  
Airway Smooth Muscle Cells ◽  
Reporter Assay ◽  
Mitogen Activated Protein ◽  
Dual Luciferase Reporter Assay

Asthma is a respiratory disease with a clinically high incidence, and repeated attacks of asthma severely affect the quality of life and even pose a threat to health, leading to severe burdens on families and even the society. A thorough understanding of the pathogenesis of asthma is essential for the prevention and treatment of asthma. This study aimed to examine the effect of the microRNA miR-27a on asthma and its relationship with mitogen activated protein kinase 4 (MAP2K4). Patients with asthma admitted to our hospital from August 2016 to August 2018 and healthy participants in the same period were included in this prospective analysis. The mRNA expression levels of miR-27a and MAP2K4 in peripheral blood were determined. Airway smooth muscle cells (ASMCs) were used to study the effects of miR-27a and MAP2K4 on cell biological behavior. The relationship between miR-27a and MAP2K4 was verified using dual-luciferase reporter assay. miR-27a expression was increased and MAP2K4 mRNA expression was decreased in asthma (P < 0.05). Increasing miR-27a expression and inhibiting MAP2K4 expression could enhance the activity of ASMCs, whereas inhibiting miR-27a expression and increasing MAP2K4 expression had the opposite effect (P < 0.05). Dual-luciferase reporter assay results showed that the fluorescence activity of MAP2K4-wild type was inhibited by increased miR-27a expression (P < 0.05). miR-27a promotes the proliferation and invasion of ASMCs by targeting MAP2K4 and is involved in the occurrence of asthma.

Evaluation of the prognostic/predictive role of tumor EGFR and KRAS mutations in Greek metastatic non-small cell lung cancer patients treated with first-line chemotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19048-e19048
Author(s):  
Helena Linardou ◽  
Paris A. Kosmidis ◽  
Vassiliki Kotoula ◽  
Vasilios Karavasilis ◽  
Anastasia G Eleftheraki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell ◽  
Egfr Mutations ◽  
Wild Type ◽  
Small Cell Lung ◽  
Kras Mutations ◽  
Predictive Role ◽  
Nsclc Patients ◽  
Line Chemotherapy

e19048 Background: KRAS mutations are reported in 20-25% of non-small cell lung cancer (NSCLC). Little is known about the prognostic/predictive role of KRAS in advanced NSCLC, with conflicting results among small studies. Recent evidence showed that KRAS mutations could predict for worse outcome in patients treated with platinum-based adjuvant chemotherapy. Methods: KRAS and EGFR genotypes were evaluated in 414 NSCLC patients with available clinical data, diagnosed from March 2000 to December 2012 (tissue blocks from the HeCOG tumor repository). KRAS and EGFR mutations were associated with clinicopathological parameters (mutated vs. wild-type). Outcome comparisons were performed in 214 metastatic patients with treatment data available, following 1st-line chemotherapy without tyrosine kinase inhibitors. Results: The majority of the patients were male (80%), current smokers (53%), with adenocarcinoma (AC) histology (65%). EGFR mutations were found in 10% and KRAS mutations in 17% of all histological types, while in AC they were 14% and 21%, respectively. Most EGFR mutations were classical (79%), while most common KRAS mutations were p.G12C (39%), p.G12D (30%) and p.G12V (15%). Two tumors had concurrent EGFR and KRAS mutations. EGFR mutations were significantly associated with female gender, AC histology and non-smoking status, as previously described. KRAS mutations were associated with AC histology and younger age (<60). At a median follow-up of 31 months, EGFR status did not show any significant associations with OS or PFS, while KRAS mutations were prognostic for worse OS compared to KRAS and EGFR wild-type tumors (HR=1.67, CI=1.08-2.59, p=0.021). This effect was also significant (p=0.022) in the presence of treatment type, with platinum-based therapy being a positive prognostic factor for OS (HR=0.62, CI=0.4-0.92, p=0.019). The association of KRAS mutations with PFS was not significant. Conclusions: EGFR and KRAS genotype incidences are presented for the first time for Greek metastatic NSCLC patients. In this setting, the presence of KRAS mutations significantly increases and platinum 1st-line treatment decreases the risk of death.

scholarly journals EIF4A3-Mediated CircRNA_100290 Promotes GC Cell Proliferation, Invasion and EMT via miR-29b-3p/ITGA11 Axis

2020 ◽  
Author(s):  
Gang Wang ◽  
Dan Sun ◽  
Wenhui Li ◽  
Yan Xin
Keyword(s):  
Cell Proliferation ◽  
Western Blot ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Reporter Assay ◽  
Qrt Pcr ◽  
Node Metastasis ◽  
Dual Luciferase Reporter Assay

Abstract Background Circular RNA (circRNA) has been reported as an important regulator in the development and progression of various carcinomas. However, the role of circRNA_100290 in gastric cancer (GC) is still unclear. This study aimed to investigate the role of circRNA_100290 in GC invasion and metastasis and its possible mechanism.Methods The expression of circRNA_100290 in GC cells and tissues were examined using quantitative real-time polymerase chain reaction (qRT-PCR). The role of circRNA_100290 in cell proliferation, migration, and invasion was evaluated on AGS and HGC-27 cell lines in vitro. Bioinformatics tools, dual-luciferase reporter assay, Western blot assay and qRT-PCR were used to explore the downstream pathways of circRNA_100290. The mechanism underlying the regulation of the expression of circRNA_100290 was explored using RNA immunoprecipitation, qRT-PCR, and Western blot assays.Results The expression of circRNA_100290 was found significantly upregulated in GC cells and 102 GC tissues, high expression of circRNA_100290 in GC was closely related to Borrmann’s types, lymph node metastasis and tumor-node-metastasis staging. In vitro, knockdown of circRNA_100290 in AGS and HGC-27 cells significantly inhibited cell proliferation, migration, and invasion. Mechanistically, dual-luciferase reporter assay confirmed a direct binding between circRNA_100290 and miR-29b-3p, which targets ITGA11, an oncogene which is closely related to epithelial–mesenchymal transition (EMT). In addition, EIF4A3, one of RNA binding proteins (RBPs), could inhibit the formation of circRNA_100290 via enriching flanking sites of circRNA_100290. Low expression of EIF4A3 in GC was related to a worse prognosis.Conclusions Elevated circRNA_100290 in GC promotes cell proliferation, invasion and EMT via miR-29b-3p/ITGA11 axi and might be regulated by EIF4A3. CircRNA_100290 might be a promising biomarker and target for GC therapy.

scholarly journals miR-454 suppresses the proliferation and invasion of ovarian cancer by targeting E2F6

2020 ◽  
Author(s):  
Yunhe An ◽  
Jun Zhang ◽  
Yanjie Tian ◽  
Baoming Li ◽  
Xiaoyan Cheng ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Luciferase Reporter ◽  
Ovarian Cancer Cells ◽  
Reporter Assay ◽  
Cancer Tissues ◽  
Dual Luciferase Reporter Assay

Abstract Background: It has been reported that hypoxia is closely related to the tumor malignancy and recurrence and regulates multiple hub genes in ovarian cancer. MicroRNA-454 (miR-454) has been confirmed to be involved in tumorigenesis and tumor development. However, the functional role of miR-454 in ovarian cancer remains unclear.Methods: The expression of miR-454 in ovarian cancer cells and serum of ovarian cancer patients was detected by RT-PCR. CCK8, colony formation, transwell, and flow cytometry assays were conducted to assess the effects of miR-454 on ovarian cancer cell proliferation, migration, invasion, and apoptosis. Dual-luciferase reporter assay was used to confirm the targeting relationship between miR-454 and E2F6. The expression pattern of E2F6 in ovarian cancer tissues was detected using immunohistochemistry assay. The relative expression of related proteins was examined using western blot analysis.Results: miR-454 was markedly down-regulated by hypoxia in ovarian cancer cells. Compared with normal serum, the expression of miR-454 was up-regulated in the serum of ovarian cancer patients, and was correlated with the clinicopathological stage of ovarian cancer patients. Next, we found that miR-454 overexpression inhibited the proliferation, migration and invasion of OVCAR3 and SKOV3 cells, as well as promoted apoptosis. In addition, the Akt/mTOR and Wnt/β-catenin signaling pathway were inhibited by miR-454. Bioinformatic analysis and dual-luciferase reporter assay confirmed that E2F6 was a target of miR-454 and negatively regulated by miR-454 in ovarian cancer cells. Moreover, immunohistochemical analysis showed that E2F6 was highly expressed in ovarian cancer tissues. Finally, we found that the increasing cell proliferation and migration triggered by E2F6 overexpression were abolished by miR-454 overexpression.Conclusion: Taken together, these results highlight the role of miR-454 as a tumor suppressor in ovarian cancer by targeting E2F6, indicating that the hypoxia/miR-454/E2F6 pathway may be a novel therapeutic approach for ovarian cancer.

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