Mir-758-5p Suppresses Glioblastoma Proliferation, Migration and Invasion by Targeting ZBTB20

Background/Aims: To determine the cellular functions and clinical significance of micro-758-5p (miR-758-5p) in glioblastoma (GBM) by targeting zinc finger and BTB domain-containing protein 20 (ZBTB20). Methods: Fifty-five paired GBM tissues and adjacent normal tissues, GBM cell lines (U118, LN-299, H4, A172, U87-MG, and U251), and normal human astrocyte cell line (HEB) were used. miR-758-5p mimics, ZBTB20 siRNA, and pcDNA3.1-ZBTB20 were transiently transduced into cancer cells independently or together. qRT-PCR was conducted to analyze the expression of miR-758-5p and ZBTB20. Luciferase reporter assays were performed to determine the effect of miR-758-5p on ZBTB20. Western blot was applied to measure the expression of ZBTB20, PCNA, and cleaved caspase3. Cell Counting Kit-8 (CCK8), colony formation, FACS, and Transwell assays were carried out to detect cellular proliferation, apoptosis, migration, and invasion. Xenograft experiments were implemented to evaluate tumor growth and metastasis in vivo. Results: miR-758-5p was significantly downregulated in GBM tissues and cell lines compared with that in adjacent normal tissues and HEB cells. miR-758-5p overexpression inhibited the proliferation, migration, and invasion of GBM cells and induced apoptosis by regulating the ZBTB20 expression. Pearson correlation analysis also confirmed that miR-758-5p was inversely correlated with ZBTB20 in GBM tissues. miR-758-5p suppressed tumor growth and metastasis in vivo. The restored ZBTB20 expression partially rescued the miR-758-5p-induced inhibition of GBM cell proliferation, migration, and invasion. Kaplan–Meier curve analysis revealed that a high miR-758-5p expression indicated an enhanced prognosis of patients with GBM. Conclusion: miR-758-5p suppressed GBM progression by targeting ZBTB20. The miR-758-5p/ZBTB20 axis might be a promising therapeutic target for GBM treatment.

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MiR-548ac Inhibits Wnt5a Expression and Promotes Proliferation of Glioma Cells Through the AKT/ERK Pathway

10.21203/rs.3.rs-448333/v1 ◽

2021 ◽

Author(s):

wen shan ◽

Haonan Li ◽

Xu Lu ◽

Xuting Wu ◽

Xinhua Zhang

Keyword(s):

Cell Proliferation ◽

Tumor Growth ◽

Malignant Tumors ◽

Glioma Cells ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Potential Strategy ◽

Tumor Growth And Metastasis

Abstract Background: Glioma one of the most frequently occurring and lethal primary malignant tumors in adults. Micro (mi)RNAs) are a newly identified modulator involved in the occurrence and progression of glioblastoma multiforme (GBM). Previous studies found that miR-548ac had a role in suppressing laryngeal and breast cancer. This study investigated the role of mir-548ac in glioma progression.Methods: The function of miR-548ac was studied by stable knockdown or overexpression of miR-548ac in GBM cells. Luciferase reporter constructs were used to investigate the correlation between Wnt5a and miR-548ac. Cell Counting Kit-8, Transwell, and colony formation assays were used to investigate Wnt5a and miR-548ac activity in glioma cells. Flow cytometry was used to describe the cell cycle. Xenograft experiments were used to evaluate tumor growth and metastasis in vivo. Western blotting was used to assess the function of the Wnt/β-catenin pathway.Results: Downregulation of miR-548ac promoted cell proliferation, migration, and invasion during GBM progression. Silencing of miR-548ac promoted expression of Wnt5a, a direct target of miR-548ac, which plays an oncogenic role in glioblastoma stem cells. Inhibiting the expression of Wat5a partially rescued the consequences of increased cell proliferation, migration, and invasion caused by miR-548ac. Tumor growth was suppressed by Wnt5a knockdown in vivo.Conclusions: miR-548ac suppressed GBM progression by targeting Wnt5a. The miR-548ac/Wnt5a axis may be a new potential strategy for glioma therapy.

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Circ_0000215 Exerts Oncogenic Function in Nasopharyngeal Carcinoma by Targeting miR-512-5p

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.688873 ◽

2021 ◽

Vol 9 ◽

Author(s):

Xinping Chen ◽

Weihua Xu ◽

Zhichao Ma ◽

Juan Zhu ◽

Junjie Hu ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Cell Lines ◽

Cell Counting ◽

Regulatory Subunit ◽

Luciferase Reporter ◽

Regulatory Function ◽

Migration And Invasion ◽

Circular Rnas

Background: Increasing circular RNAs (circRNAs) are reported to participate in cancer progression. Nonetheless, the role of circRNAs in nasopharyngeal carcinoma (NPC) has not been fully clarified. This work is aimed to probe the role of circ_0000215 in NPC.Methods: Circ_0000215 expression in NPC tissues and cell lines was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8) assay, 5-bromo-2′-deoxyuridine (BrdU) assay, scratch healing assay and Transwell experiment were executed to investigate the regulatory function of circ_0000215 on the proliferation, migration and invasion of NPC cells. RNA immunoprecipitation (RIP), pull-down and dual-luciferase reporter experiments were utilized to determine the binding relationship between circ_0000215 and miR-512-5p, and between miR-512-5p and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) 3′UTR. The effects of circ_0000215 on NPC growth and metastasis in vivo were examined with nude mice model. Western blot was applied to detect the regulatory effects of circ_0000215 and miR-512-5p on PIK3R1 expression.Results: Circ_0000215 was overexpressed in NPC tissues and cell lines. The functional experiments confirmed that knockdown of circ_0000215 impeded the growth and metastasis of NPC cells in vitro and in vivo. Additionally, circ_0000215 could also work as a molecular sponge to repress miR-512-5p expression. PIK3R1 was validated as a target gene of miR-512-5p, and circ_0000215 could increase the expression level of PIK3R1 in NPC cells via suppressing miR-512-5p.Conclusion: Circ_0000215 is overexpressed in NPC and exerts oncogenic effects in NPC through regulating miR-512-5p/PIK3R1 axis.

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Circ_0015756 promotes the progression of ovarian cancer by regulating miR-942-5p/CUL4B pathway

Cancer Cell International ◽

10.1186/s12935-020-01666-1 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Zhenhua Du ◽

Lei Wang ◽

Yu Xia

Keyword(s):

Ovarian Cancer ◽

Tumor Growth ◽

Western Blot ◽

Gynecologic Cancer ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Circular Rnas ◽

Western Blot Assay

Abstract Background Ovarian cancer (OC) is the gynecologic cancer with the highest mortality. Circular RNAs (circRNAs) play a vital role in the development and progression of cancer. This study aimed to explore the potential role of circ_0015756 in OC and its molecular mechanism. Methods The levels of circ_0015756, microRNA-942-5p (miR-942-5p) and Cullin 4B (CUL4B) were determined by quantitative real-time PCR (qRT-PCR) or Western blot assay. Cell proliferation, apoptosis, migration and invasion were assessed by Cell Counting Kit-8 (CCK-8), colony formation assay, flow cytometry and transwell assay. The levels of proliferation-related and metastasis-related proteins were measured by Western blot assay. The relationship between miR-942-5p and circ_0015756 or CUL4B was verified by dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay. Xenograft assay was used to analyze tumor growth in vivo. Results Circ_0015756 and CUL4B levels were increased, while miR-942-5p level was decreased in OC tissues and cells. Depletion of circ_0015756 suppressed proliferation, migration and invasion and promoted apoptosis in OC cells. Down-regulation of circ_0015756 hindered OC cell progression via modulating miR-942-5p. Also, up-regulation of miR-942-5p impeded OC cell development by targeting CUL4B. Mechanistically, circ_0015756 up-regulated CUL4B via sponging miR-942-5p. Moreover, circ_0015756 silencing inhibited tumor growth in vivo. Conclusion Knockdown of circ_0015756 suppressed OC progression via regulating miR-942-5p/CUL4B axis, suggesting that circ_0015756 might be a potential therapeutic target for ovarian cancer.

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MicroRNA-183-5p contributes to malignant progression through targeting PDCD4 in human hepatocellular carcinoma

Bioscience Reports ◽

10.1042/bsr20201761 ◽

2020 ◽

Vol 40 (10) ◽

Author(s):

Xiaohui Duan ◽

Wei Li ◽

Peng Hu ◽

Bo Jiang ◽

Jianhui Yang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Tumor Growth ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Clinical Samples ◽

Hcc Cells

Abstract Hepatocellular carcinoma (HCC) remains one of the most common malignant tumors worldwide. The present study aimed to investigate the biological role of microRNA-183-5p (miR-183-5p), a novel tumor-related microRNA (miRNA), in HCC and illuminate the possible molecular mechanisms. The expression patterns of miR-183-5p in clinical samples were characterized using qPCR analysis. Kaplan–Meier survival curve was applied to evaluate the correlation between miR-183-5p expression and overall survival of HCC patients. Effects of miR-183-5p knockdown on HCC cell proliferation, apoptosis, migration and invasion capabilities were determined via Cell Counting Kit-8 (CCK8) assays, flow cytometry, scratch wound healing assays and Transwell invasion assays, respectively. Mouse neoplasm transplantation models were established to assess the effects of miR-183-5p knockdown on tumor growth in vivo. Bioinformatics analysis, dual-luciferase reporter assays and rescue assays were performed for mechanistic researches. Results showed that miR-183-5p was highly expressed in tumorous tissues compared with adjacent normal tissues. Elevated miR-183-5p expression correlated with shorter overall survival of HCC patients. Moreover, miR-183-5p knockdown significantly suppressed proliferation, survival, migration and invasion of HCC cells compared with negative control treatment. Consistently, miR-183-5p knockdown restrained tumor growth in vivo. Furthermore, programmed cell death factor 4 (PDCD4) was identified as a direct target of miR-183-5p. Additionally, PDCD4 down-regulation was observed to abrogate the inhibitory effects of miR-183-5p knockdown on malignant phenotypes of HCC cells. Collectively, our data suggest that miR-183-5p may exert an oncogenic role in HCC through directly targeting PDCD4. The current study may offer some new insights into understanding the role of miR-183-5p in HCC.

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Long Noncoding RNA FER1L4 Suppresses Tumorigenesis by Regulating the Expression of PTEN Targeting miR-18a-5p in Osteosarcoma

Cellular Physiology and Biochemistry ◽

10.1159/000495554 ◽

2018 ◽

Vol 51 (3) ◽

pp. 1364-1375 ◽

Cited By ~ 20

Author(s):

Dan Fei ◽

Xiaona Zhang ◽

Jinxiang Liu ◽

Long Tan ◽

Jie Xing ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Lines ◽

Colony Formation ◽

Underlying Mechanism ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Qrt Pcr

Background/Aims: Novel long non-coding RNA Fer-1-like protein 4 (FER1L4) has been reported to play crucial regulatory roles in tumor progression. However, its clinical significance and biological role in osteosarcoma (OS) is completely unknown. The aim of the present study was to investigate the role of FER1L4 in OS progression and the underlying mechanism. Methods: We analyzed the expression levels of FER1L4 in tissues of OS patients and cell lines via quantitative RT-PCR (qRT-PCR). The effect of FER1L4 on cell proliferation, colony formation, migration and invasion was analyzed by cell counting kit-8 (CCK-8), colony formation, wound healing and transwell invasion assay, respectively. Novel targets of FER1L4 were selected through a bioinformatics soft and confirmed using a dual-luciferase reporter system and qRT-PCR. To detect the role of FER1L4 in vivo tumorigenesis, tumor xenografts were created. Results: We found that the expression of FER1L4 was significantly downregulated in OS tissues and cell lines; moreover, low expression of FER1L4 was associated with advanced tumor-nude-metastasis (TNM) stage, lymph node metastases, and poor overall survival. Functional assays showed that upregulation of FER1L4 significantly inhibited OS cell proliferation, colony formation, migration, and invasion in vitro, as well as suppressed tumor growth in vivo. Assays performed to determine the underlying mechanism, indicated that FER1L4 interacted directly with miR-18a-5p. Subsequently, we found that FER1L4 significantly increased PTEN expression, a known target of miR-18a-5p, in OS cells. Furthermore, PTEN was found to be down-regulated, and positively correlated with FER1L4 in OS tissues. Conclusion: These findings suggest that FER1L4, acting as a competing endogenous RNA (ceRNA) of miR-18a-5p, exerts its anti-cancer role by modulating the expression of PTEN. Thus, FER1L4 may be a novel target for the prevention and treatment of OS.

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Circular RNA Hsa_Circ_0007444 Inhibits Tumor Progression Through MiR-23a-3p/DICER1 in Ovarian Cancer

10.21203/rs.3.rs-955306/v1 ◽

2021 ◽

Author(s):

Min Zhang ◽

Yu Sun ◽

Hanzi Xu ◽

Yaqian Shi ◽

Rong Shen ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Proliferation ◽

Tumor Growth ◽

Cell Lines ◽

Xenograft Model ◽

Cell Counting ◽

Luciferase Reporter ◽

Ovarian Cancer Cells ◽

Mouse Xenograft Model

Abstract Background: Circular RNAs are a class of non-coding regulatory RNAs reported to be involved in cancer development and progression. Previous studies, including our own, have indicated that hsa_circ_0007444 was downregulated in ovarian cancer (OC) tissues. Herein, we demonstrated another mechanism of hsa_circ_0007444 in ovarian cancer.Methods: The expression of hsa_circ_0007444, miR-23a-3p, and DICER1 were determined by quantitative real-time PCR. Cell proliferation, invasion, migration, and apoptosis were examined by cell counting kit 8, transwell, and flow cytometry assays. The roles of hsa_circ_0007444 in tumor growth and metastasis were assessed in vivo using a nude mouse xenograft model. The bioinformatics tools were employed to predict the binding sites, which were then verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assays. DICER1 protein level was measured by western blot. Results: Hsa_circ_0007444 was downregulated in ovarian cancer cell lines compared with normal ovarian epithelial cell lines. Also, gain- and loss-of-function results indicated that hsa_circ_0007444 inhibited cell proliferation, invasion, migration, increased cell apoptosis of ovarian cancer cells in vitro, and impaired tumor growth and lung metastasis in vivo. Additionally, the results of the bioinformatics analysis, RIP, dual-luciferase reporter, and rescue assays confirmed that hsa_circ_0007444 could interact with AGO2 and sponge miR-23a-3p, thereby upregulating DICER1 expression, which was an important tumor suppressor in ovarian cancer.Conclusion: We found that overexpressed hsa_circ_0007444 could inhibit ovarian cancer progression through the hsa_circ_0007444/miR-23a-3p/DICER1 axis.

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Silencing of hsa_circ_0009035 suppresses cervicalprogression and enhances radiosensitivity through miR-889-3p-dependent regulation of HOXB7

Molecular and Cellular Biology ◽

10.1128/mcb.00631-20 ◽

2021 ◽

Author(s):

Xia Zhao ◽

Weilei Dong ◽

Guifang Luo ◽

Jing Xie ◽

Jie Liu ◽

...

Keyword(s):

Cell Proliferation ◽

Tumor Growth ◽

Colony Formation ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Circular Rnas ◽

The Impact

Circular RNAs (circRNAs), a novel type of endogenous non-coding RNAs, have been identified as critical regulators in human carcinogenesis. Here, we investigated the precise actions of hsa_circ_0009035 in the progression and radioresistance of cervical cancer (CC). The levels of hsa_circ_0009035, microRNA (miR)-889-3p and homeobox B7 (HOXB7) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Ribonuclease R (RNase R) and Actinomycin D assays were used to assess the stability of hsa_circ_0009035. Cell proliferation, cell cycle progression, apoptosis, migration and invasion were gauged by the Cell Counting Kit-8 (CCK-8), flow cytometry and transwell assays, respectively. Cell colony formation and survival were determined by the colony formation assay. Targeted correlations among hsa_circ_0009035, miR-889-3p and HOXB7 were examined by the dual-luciferase reporter, RNA immunoprecipitation (RIP) or RNA pull-down assay. Animal studies were performed to evaluate the impact of hsa_circ_0009035 on tumor growth. We found that hsa_circ_0009035 was highly expressed in CC tissues and cells, and it was associated with the radioresistance of CC patients. Moreover, the silencing of hsa_circ_0009035 inhibited CC cell proliferation, migration, invasion, and enhanced apoptosis and radiosensitivity in vitro and weakened tumor growth in vivo. Mechanistically, hsa_circ_0009035 directly targeted miR-889-3p by binding to miR-889-3p, and hsa_circ_0009035 modulated HOXB7 expression through miR-889-3p. HOXB7 was a functional target of miR-889-3p in regulating CC progression and radioresistance in vitro, and hsa_circ_0009035 modulated CC progression and radioresistance in vitro by miR-889-3p. Our current study first identified hsa_circ_0009035 as an important regulation of CC progression and radioresistance at least in part through targeting the miR-889-3p/HOXB7 axis, highlighting its significance as a potential therapeutic target for CC treatment.

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miR-548ac Inhibit Wnt5a Expression and Promotes Proliferation of Glioma Cells through the AKT/ERK Pathway

10.21203/rs.3.rs-148995/v1 ◽

2021 ◽

Author(s):

Wen Shan ◽

Haonan Li ◽

Xu Lu ◽

Xuting Wu ◽

Xinhua Zhang

Keyword(s):

Malignant Tumors ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Wnt5a Expression ◽

Kaplan Meier ◽

Glioma Xenograft ◽

Potential Strategy ◽

Tumor Growth And Metastasis

Abstract Background Glioma is one of the most frequently occurring and lethal primary malignant tumors. MicroRNAs (miRNAs) are a newly identified modulator involved in the formation and progression of glioma. Methods Stable knockdown or over-expression of miR-548ac in U87 glioblastoma multiforme (GBM) cells was used to explore the function of miR-548ac in the expression of Wnt5a. Luciferase reporter constructs were used to investigate the correlation between Wnt5a expression and miR-548ac. Cell Counting Kit-8 assays, Transwell assays, colony formation assays and flow cytometry were used to investigate the functions of Wnt5a and miR-548ac in glioma. Xenograft experiments were used to evaluate tumor growth and metastasis in vivo. Western blotting was used to assess the function of the Wnt/β-catenin pathway. Results miR-548ac overexpression down-regulated the proliferation, migration and invasion of GBM cells. In addition, knockdown of miR-548ac promoted expression of Wat5a, a direct target of miR-548ac, which plays an oncogenic role in glioblastoma stem cells. Reduced Wan5a expression partially rescued the miR-548ac-induced enhancement of GBM cell proliferation, migration and invasion. Kaplan–Meier curve analysis revealed that high miR-548ac expression was associated with poor prognosis of patients with GBM. Conclusions miR-548ac suppresses GBM progression by targeting Wan5a. The miR-548ac/Wnt5a axis may be a new potential strategy for glioma therapy.

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Fibroblast Growth Factor 11 (FGF11) Promotes Non-small Cell Lung Cancer (NSCLC) Progression by Regulating Hypoxia Signaling Pathway

10.21203/rs.3.rs-414555/v1 ◽

2021 ◽

Author(s):

Xiaowei Wu ◽

Minjie Li ◽

Yu Deng ◽

Shun Ke ◽

Fan Li ◽

...

Keyword(s):

Cell Proliferation ◽

Tumor Growth ◽

Signaling Pathway ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Normal Tissues ◽

Tumor Tissues ◽

Hypoxia Signaling

Abstract Background: Recently, accumulating studies highlight the critical regulatory roles of fibroblast growth factors (FGF), and a series of FGF, participated in the progression of multiple human cancers, including non-small cell lung cancer (NSCLC). Methods: Gene transcriptome analysis was used to identify the differential expression of FGF11 in NSCLC tumor tissues, GSE75037 and GSE81089 database analysis was performed on NSCLC tumor tissues and adjacent normal tissues to validate the expression of FGF11. Then, we selected 100 cases of NSCLC tumor tissues and 30 cases of matched adjacent normal tissues to confirm the mRNA and protein level of FGF11 by qRT-PCR and immunohistochemistry. Bioinformatics analysis and dual luciferase reporter analysis was also performed to examine the direct regulatory of FGF11 by miR-525-5p. CCK-8 and transwell assay was also performed to detect the cell proliferation, migration and invasion. Signal pathway analysis was also investigated the effect of FGF11 on NSCLC cell proliferation was associated with the hypoxia signaling pathway. The role of FGF11 in NSCLC tumor growth was further explored by in vivo study.Results: FGF11 was overexpressed in NSCLC tumor tissues and tumor cell lines, the high expression of FGF11 was closely associated with poor overall survival of NSCLC patients. In vitro loss- and gain- of function experiments demonstrated that FGF11 knockdown inhibited, whereas FGF11 overexpression promoted the proliferation, migration and invasion of NSCLC cells. The dual luciferase reporter assay confirmed that FGF11 was downregulated by miR-525-5p, and the effect of FGF11 on cell proliferation, migration and invasion could be interfered by miR-525-5p. We further found that FGF11 had significant correlation with hypoxia signaling pathway activation, meanwhile regulating HIF-1α. Further experiments implicated that the oncogenic role of FGF11 could be blocked via interfering of HIF-1α in NSCLC cells. Moreover, knockdown of FGF11 suppressed NSCLC tumor growth whereas overexpression of FGF11 promoted tumor growth in vivo. Conclusions: FGF11 might be functioned as an oncogene in tumor development, the findings of our study revealed a novel regulatory mechanism of FGF11 involved in hypoxia signaling pathway, which offers novel strategies for the treatment of NSCLC.

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Doxorubicin inhibits osteosarcoma progression by regulating circ_0000006/miR-646/ BDNF axis

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-021-02782-y ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Abulimiti Amuti ◽

Dehu Liu ◽

Ayiguli Maimaiti ◽

Yao Yu ◽

Yalikun Yasen ◽

...

Keyword(s):

Cell Proliferation ◽

Protein Expression ◽

Tumor Growth ◽

Cell Apoptosis ◽

Tumor Formation ◽

Cell Counting ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Control Groups

Abstract Background Osteosarcoma (OS) is the most common aggressive bone tumor in children and teenagers. Doxorubicin (DOX) is a chemotherapeutic drug for OS. This study aims to reveal the effects and underneath mechanism of DOX treatment in OS progression. Methods The expression of circular_0000006 (circ_0000006), microRNA-646 (miR-646) and brain-derived neurotrophic factor (BDNF) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). BDNF protein expression was determined by western blot. Cell proliferation was illustrated by cell counting kit-8 (CCK-8) and cell colony formation assays. Cell migration and invasion were revealed by transwell migration and wound-healing assays and transwell invasion assay, respectively. Cell apoptosis was demonstrated by flow cytometry analysis. The binding relationship of miR-646 and circ_0000006 or BDNF was predicted by circRNA interactome and targetscan online database, respectively, and verified by dual-luciferase reporter assay. The effects of circ_0000006 knockdown on tumor growth in vivo were manifested by in vivo tumor formation assay. Results Circ_0000006 expression and the mRNA and protein levels of BDNF were dramatically upregulated, and miR-646 expression was effectively downregulated in OS tissues or cells compared with control groups. Circ_0000006 expression and BDNF protein expression were lower, and miR-646 expression was higher in DOX treatment groups than in control groups in OS cells. Circ_0000006 knockdown repressed cell proliferation, migration and invasion, whereas promoted cell apoptosis under DOX treatment in OS cells; however, these effects were attenuated by miR-646 inhibitor. Additionally, circ_0000006 sponged miR-646 to bind to BDNF. Circ_0000006 silencing suppressed tumor growth in vivo. Conclusion Circ_0000006 knockdown promoted DOX-mediated effects on OS development by miR-646/BDNF pathway, which provided a theoretical basis in treating OS with DOX.

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