Long Noncoding RNA SNHG16 Promotes Cell Proliferation by Sponging MicroRNA-205 and Upregulating ZEB1 Expression in Osteosarcoma

Background/Aims: Long noncoding RNAs (lncRNAs) have been a research hotspot, as they play important roles in tumor development. However, their expression pattern and biological function in osteosarcoma have not yet been clarified. Methods: Differentially expressed lncRNAs in osteosarcoma and paracarcinoma tissues were identified by screening an lncRNA microarray, and candidate lncRNAs were verified by quantitative real-time PCR (qRT-PCR). A series of bioinformatics and molecular biological methods were adopted to investigate the interaction among lncRNA, microRNA (miRNA), and miRNA target genes during the development and occurrence of osteosarcoma. Cell viability was measured using a Cell Counting Kit-8 assay. Results: Chip microarray screening combined with the validation of differentially expressed candidate lncRNAs showed that the lncRNA small nucleolar RNA host gene 16 (SNHG16) had the largest fold change. SNHG16 was highly expressed in osteosarcoma tissues and cell lines, and its downregulation led to the suppressed proliferation of osteosarcoma cells. Further investigations revealed that SNHG16 could upregulate zinc finger E-box-binding homeobox 1 (ZEB1) expression by acting as an endogenous sponge of miR-205. Moreover, rescue assays proved that the effects of SNHG16 on the proliferation of osteosarcoma cells were dependent on miR-205. Conclusion: SNHG16 can significantly enhance the proliferation of osteosarcoma cells. In addition, SNHG16, miR-205, and ZEB1 interact in a common pathway during the development and occurrence of osteosarcoma, providing novel targets for intervention in the treatment of osteosarcoma.

Download Full-text

LncRNA SNHG15 contributes to doxorubicin resistance of osteosarcoma cells through targeting the miR-381-3p/GFRA1 axis

Open Life Sciences ◽

10.1515/biol-2020-0086 ◽

2020 ◽

Vol 15 (1) ◽

pp. 871-883

Author(s):

Jinshan Zhang ◽

Dan Rao ◽

Haibo Ma ◽

Defeng Kong ◽

Xiaoming Xu ◽

...

Keyword(s):

Cell Lines ◽

Noncoding Rna ◽

Xenograft Model ◽

Inhibitory Effect ◽

Cell Counting ◽

Luciferase Reporter ◽

Osteosarcoma Cell ◽

Osteosarcoma Cells

AbstractBackgroundOsteosarcoma is a common primary malignant bone cancer. Long noncoding RNA small nucleolar RNA host gene 15 (SNHG15) has been reported to play an oncogenic role in many cancers. Nevertheless, the role of SNHG15 in the doxorubicin (DXR) resistance of osteosarcoma cells has not been fully addressed.MethodsCell Counting Kit-8 assay was conducted to measure the half-maximal inhibitory concentration value of DXR in osteosarcoma cells. Western blotting was carried out to examine the levels of autophagy-related proteins and GDNF family receptor alpha-1 (GFRA1). Quantitative reverse transcription-polymerase chain reaction was performed to determine the levels of SNHG15, miR-381-3p, and GFRA1. The proliferation of osteosarcoma cells was measured by MTT assay. The binding sites between miR-381-3p and SNHG15 or GFRA1 were predicted by Starbase bioinformatics software, and the interaction was confirmed by dual-luciferase reporter assay. Murine xenograft model was established to validate the function of SNHG15 in vivo.ResultsAutophagy inhibitor 3-methyladenine sensitized DXR-resistant osteosarcoma cell lines to DXR. SNHG15 was upregulated in DXR-resistant osteosarcoma tissues and cell lines. SNHG15 knockdown inhibited the proliferation, DXR resistance, and autophagy of osteosarcoma cells. MiR-381-3p was a direct target of SNHG15, and GFRA1 bound to miR-381-3p in osteosarcoma cells. SNHG15 contributed to DXR resistance through the miR-381-3p/GFRA1 axis in vitro. SNHG15 depletion contributed to the inhibitory effect of DXR on osteosarcoma tumor growth through the miR-381-3p/GFRA1 axis in vivo.ConclusionsSNHG15 enhanced the DXR resistance of osteosarcoma cells through elevating the autophagy via targeting the miR-381-3p/GFRA1 axis. Restoration of miR-381-3p expression might be an underlying therapeutic strategy to overcome the DXR resistance of osteosarcoma.

Download Full-text

Differentially Expressed Long Noncoding RNAs Involved in FUBP1 Promoting Hepatocellular Carcinoma Cells Proliferation

BioMed Research International ◽

10.1155/2021/6664519 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Xianpeng Li ◽

Huaixi Yu ◽

Feng Xu ◽

Yifeng Wu ◽

Jifang Sheng

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Lines ◽

Noncoding Rna ◽

Target Genes ◽

Expression Profiles ◽

Differentially Expressed ◽

Cell Counting ◽

Rt Pcr ◽

Upstream Element ◽

Hcc Cells

Background. Far upstream element-binding protein 1 (FUBP1) is reported to be involved in cancer development by regulating the transcription of c-myc gene through binding to far upstream element. Highly expressed FUBP1 was negatively correlated with survival rate of patients with hepatocellular carcinoma (HCC) and could promote the proliferation of HCC cells. However, the downstream mechanism of FUBP1 has not yet been clearly explained. This study is aimed at identifying the expression profiles of long noncoding RNA (lncRNA) in HCC cells in response to FUBP1 overexpression and at investigating the possible lncRNAs that participated in cell proliferation process regulated by FUBP1. Methods. The overexpression of FUBP1 was mediated by lentiviral infection on 3 different types of HCC cell lines (MHCC97-H, MHCC97-L, and Huh-7). The expression of target genes was detected by quantitative reverse transcription-PCR (RT-PCR) and western blotting assays. Microarray and quantitative RT-PCR were applied to screen the differentially expressed lncRNAs in HCC cells after FUBP1 overexpression. The Cell Counting Kit-8 assay was used to confirm the growth vitality of HCC cells. Results. The growth vitality of HCC cells was significantly increased after lentivirus infection. A total of 12 lncRNAs had the same expression trend in the 3 HCC cell lines in response to FUBP1 overexpression, including 3 upregulated lncRNAs and 9 downregulated lncRNAs. Coexpression analysis of dysregulated lncRNAs-mRNAs network showed that lnc-LYZ-2 was the lncRNA most relevant to FUBP1. Inhibition of lnc-LYZ-2 could significantly relieve the proproliferation effect of FUBP1 on HCC cells, suggesting that lnc-LYZ-2 was partially involved in proproliferation regulation of FUBP1. Conclusions. Our results indicated that FUBP1 induced the abnormal expression of lncRNAs and the FUBP1-lncRNAs coexpression network in HCC cells, which could provide theoretical and experimental basis for FUBP1-lncRNAs network involved in HCC development.

Download Full-text

Genomewide analysis of circular RNA in pituitaries of normal and heat-stressed sows

BMC Genomics ◽

10.1186/s12864-019-6377-7 ◽

2019 ◽

Vol 20 (1) ◽

Author(s):

Haojie Zhang ◽

Baoyu Hu ◽

Jiali Xiong ◽

Ting Chen ◽

Qianyun Xi ◽

...

Keyword(s):

Heat Stress ◽

Heat Shock ◽

Heat Shock Protein ◽

Noncoding Rna ◽

Target Genes ◽

Hormone Secretion ◽

Circular Rna ◽

Differentially Expressed ◽

Pcr Analysis ◽

Pituitary Hormone

Abstract Background As a newly characterized type of noncoding RNA, circular RNA (circRNA) has been shown to have functions in diverse biological processes of animals. It has been reported that several noncoding RNAs may regulate animals’ response to heat stress which can be easily induced by hyperthermia in summer. However, the expression and functions of circRNAs in the pituitary of sows and whether they participate in heat stress adaption are still unclear. Results In this study, we found that high temperature over the thermoneutral zone of sows during the summer increased the serum heat shock protein 70 (HSP70) level, decreased the superoxide dismutase (SOD) vitality and prolactin (PRL) concentration, and induced heat stress in sows. Then, we explored circRNA in the pituitary of heat-stressed and normal sows using RNA sequencing and bioinformatics analysis. In total, 12,035 circRNAs were detected, with 59 circRNAs differentially expressed, including 42 up-regulated and 17 down-regulated circRNAs in pituitaries of the heat-stressed sows. Six randomly selected circRNAs were identified through reverse transcription PCR followed by DNA sequencing and other 7 randomly selected differentially expressed circRNAs were verified by quantitative real-time PCR analysis. The predicted target genes regulated by circRNAs through sponging microRNAs (miRNAs) were enriched in metabolic pathway. Furthermore, the predicted circRNA–miRNA–mRNA interactions showed that some circRNAs might sponge miRNAs to regulate pituitary-specific genes and heat shock protein family members, indicating circRNA’s roles in pituitary hormone secretion and heat stress response. Conclusions Our results provided a meaningful reference to understand the functions of circRNA in the porcine pituitary and the mechanisms by which circRNA may participate in animals’ response to heat stress.

Download Full-text

miR-451a Inhibits the Growth and Invasion of Osteosarcoma via Targeting TRIM66

Technology in Cancer Research & Treatment ◽

10.1177/1533033819870209 ◽

2019 ◽

Vol 18 ◽

pp. 153303381987020 ◽

Cited By ~ 1

Author(s):

Xiao Ma ◽

Dan Li ◽

Yan Gao ◽

Cheng Liu

Keyword(s):

Cell Lines ◽

Luciferase Activity ◽

Cell Counting ◽

Osteosarcoma Cell ◽

Reporter Assay ◽

Osteosarcoma Cells ◽

Transwell Assay ◽

Tripartite Motif ◽

Regulatory Effects ◽

Novel Therapeutic

The importance of microRNAs in regulating osteosarcoma development has been studied in recent years. However, the function of microRNA-451a in osteosarcoma growth is rarely investigated. Here, we explored the expression of microRNA-451a in osteosarcoma cell lines. Bioinformatic software, luciferase activity reporter assay, and Western blot were conducted to determine the association between microRNA-451a and tripartite motif-containing 66. Cell Counting Kit-8 assay and transwell assay were used to explore the regulatory effects of microRNA-451a on osteosarcoma cells. Moreover, we explored whether microRNA-451a modulates osteosarcoma cell biological activity by regulating tripartite motif-containing 66. The expression of microRNA-451a was found to be downregulated in osteosarcoma and negatively regulated the expression of tripartite motif-containing 66. Tripartite motif-containing 66 was further validated as a target of microRNA-451a. MicroRNA-451a inhibits the growth and invasion of osteosarcoma cell lines through targeting tripartite motif-containing 66. The miR-451a targets tripartite motif-containing 66 may provide novel therapeutic targets for the treatment of osteosarcoma.

Download Full-text

Exosomal miR-199a-5p Inhibits Tumorigenesis and Angiogenesis by Targeting VEGFA in Osteosarcoma

10.21203/rs.3.rs-912512/v1 ◽

2021 ◽

Author(s):

Lu Zhang ◽

Hongxin Cao ◽

Guanghui Gu ◽

Dehui Hou ◽

Yunhao You ◽

...

Keyword(s):

Molecular Mechanisms ◽

Target Genes ◽

Enrichment Analysis ◽

Luciferase Reporter ◽

Pathway Enrichment Analysis ◽

Osteosarcoma Cell ◽

Plasma Samples ◽

Osteosarcoma Cells ◽

Hub Genes

Abstract Background: Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents. microRNAs have been found to play a vital role in tumor angiogenesis. Here, we investigated the effects of miR-199a-5p on tumor growth and angiogenesis in osteosarcoma. Furthermore, the underlying molecular mechanisms and signaling pathways were explored.Methods: The datasets were extracted from the Gene Expression Omnibus and the differentially expressed miRNAs (DEmiRNAs) were screened out by the GEO2R online platform. The potential target genes were predicted using the miRTarBase database. The predicted target genes were further analyzed by Gene Ontology and pathway enrichment analysis and a regulatory network of DEmiRNAs and their target genes was constructed. In addition, the effects of osteosarcoma cell derived exosomal miR-199a-5p on the proliferation, migration and neovascularization of HUVECs were evaluated by conducting EdU assays, Transwell experiments and tube formation assays. A dual-luciferase reporter assay was performed to detect whether VEGFA was the direct target of miR-199a-5p. Furthermore, in vivo xenograft models were established to further investigate the intrinsic role of miR-199a-5p in osteosarcoma tumorigenesis and angiogenesis. Results: A total of 149 DE-miRNAs were screened out, including 136 upregulated miRNAs and 13 downregulated miRNAs in human osteosarcoma plasma samples compared with normal plasma samples. A total of 1313 target genes of the top three upregulated and downregulated miRNAs were predicted. In the PPI network, the top 10 hub nodes with higher degrees were identified as hub genes, such as TP53 and VEGFA. By constructing the miRNA-hub gene network, we found that most of hub genes could be potentially modulated by miR-663a, miR-199a-5p and miR-223-3p. In addition, we found that the expression level of miR-199a-5p in exosomes derived from osteosarcoma cells was remarkably higher than the osteosarcoma cells, and the exosomes derived from osteosarcoma cells were transported to HUVECs. Overexpression of miR-199a-5p could significantly inhibited HUVEC proliferation, migration and neovascularization, whereas downregulation of miR-199a-5p expression exerted the opposite effect. Moreover, the in vivo results verified that overexpression of miR-199a-5p in osteosarcoma cells could suppress the growth and angiogenesis of tumors. Conclusion: Our results demonstrated that miR-199a-5p could be transported from osteosarcoma cells to HUVECs through exosomes, subsequently targeting VEGFA and inhibiting the growth and angiogenesis of osteosarcoma. Therefore, miR-199a-5p may act as a biomarker in the diagnosis and treatment of osteosarcoma.

Download Full-text

Transcriptome analysis of messenger RNA and long noncoding RNA related to different developmental stages of tail adipose tissues of sunite sheep

10.21203/rs.3.rs-131480/v1 ◽

2020 ◽

Author(s):

Xige He ◽

Rihan Wu ◽

Yueying Yun ◽

Xia Qin ◽

Lu Chen ◽

...

Keyword(s):

Long Noncoding Rna ◽

Messenger Rna ◽

Noncoding Rna ◽

Target Genes ◽

Early Stage ◽

Expression Profiles ◽

Theoretical Data ◽

Differentially Expressed ◽

Growth Stages ◽

Complex Biological Process

Abstract Background: Sunite sheep are a fat-tailed sheep species with a low percentage of intramuscular fat and good quality lean meat, and their tail fat can be used as a source of dietary fat by humans. To understand the potential regulatory mechanism of different growth stages of tail fat in Sunite sheep, we performed high-throughput RNA sequencing to characterize the long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression profiles of the sheep tail fat at the age of 6 months, 18 months, and 30 months.Results: A total of 223 differentially expressed genes (DEGs) and 148 differentially expressed lncRNAs were found in the tail fat of 6-, 18-, and 30-month-old sheep (false discovery rate < 0.05, |Fold Change| ≥ 2). Based on the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, we found that fat-related DEGs were mainly expressed at 6 months of age, and gradually decreased at 18 and 30 months of age. The target gene prediction analysis shows that most of the lncRNAs target more than 20 mRNAs as their trans-regulators (53 mRNAs at most). Further, we obtained several fat-related differentially-expressed target genes; these target genes interact with different differentially expressed lncRNAs at various ages and play an important role in the development of tail fat. Based on the DEGs and differentially expressed lncRNAs, we established three co-expression networks for each comparison group. Conclusions: Finally, we conclude that the development of the sheep tail fat is more active during the early stage of growth and gradually decreases with the increase in age. The mutual regulation of lncRNAs and mRNAs may play a key role in this complex biological process, and our findings will provide some basic theoretical data for future studies on tail fat development of fat-tailed sheep.

Download Full-text

PiRNA MW557525 Promotes the Vitality and Pluripotency of Piwil2-iCSCs by Regulating NOP56.

10.21203/rs.3.rs-439016/v1 ◽

2021 ◽

Author(s):

Zhaoxia Zhang ◽

Zhang Wang ◽

Xiaojun Tan ◽

Liming Jin ◽

Zhaoying Wang ◽

...

Keyword(s):

Target Gene ◽

High Throughput Sequencing ◽

Target Genes ◽

Tumor Development ◽

High Mobility ◽

P Element ◽

Cell Counting ◽

Luciferase Reporter ◽

Go Analysis ◽

Protein Levels

Abstract Objective Cancer stem cells (CSCs) play an important role in tumor development. Some studies have demonstrated that P-element–induced wimpy testis (Piwi)–interacting ribonucleic acids (piRNAs) participate in the progression of various cancers. However, the detailed function of piRNAs in CSCs requires further investigation. The aim of the present study was to investigate the effect of the uknown upregulated piRNA MW557525 and its predicted target gene nucleolar protein 56 (NOP56) inPiwi-like protein 2 (Piwil2)–induced CSCs (Piwil2-iCSCs).Methods We screened differential piRNAs of Piwil2-iCSCs using high-throughput sequencing (HTS). Target genes were predicted by the miRanda algorithm and subjected to Gene Ontology (GO) analysis. One of the differential piRNAs, MW557525, and its target gene NOP56 were transfected and silenced in Piwil2-iCSCs, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to detect expression levels of piRNA MW557525 and NOP56 in Piwil2-iCSCs after transfection. We measured protein levels of NOP56 in different groups via Western blot (WB), verified interactions using a dual luciferase reporter assay (LRA) and investigated the effect of piRNA MW557525 and NOP56 on Piwil2-iCSC proliferation using a Cell Counting Kit-8 (CCK-8). In addition, we evaluated cell migratory and invasive abilities via transwell assay and detected cell apoptotic ability via flow cytometry (FCM) assay. Protein levels of Cluster of Differentiation 24 (CD24), CD133, Krüppel-like factor 4 (KLF4) and sex-determining region Y–related high-mobility group (HMG) box 12 (SOX2) were measured to evaluate the change in Piwil2-iCSC pluripotency after transfection.Results Via HTS, we screened out 204 differential piRNAs, and miRanda predicted 77 target genes. GO analysis showed that the biological processes (BPs) of these target genes were mainly involved in regulating the calcium concentration of cells and their molecular functions (MFs) were mainly involved in ATPase activity.The expression of piRNA MW557525 and NOP56 were significantly upregulated,and piRNA MW557525 was negatively associated with NOP56 in Piwil2-iCSCs. PiRNA MW557525 promoted proliferation, migration, invasion and pluripotency and inhibited apoptosis, while NOP56 suppressed proliferation, migration, invasion and pluripotency and induced apoptosis, in Piwil2-iCSCs.Conclusion Taken together, these findings suggested that piRNA MW557525 promoted and maintained the vitality and pluripotency of Piwil2-iCSCs, while NOP56 inhibited these characteristics. Therefore, piRNA MW557525 might be a novel therapeutic target in Piwil2-iCSCs.

Download Full-text

Genome-Wide Detection of Key Genes and Epigenetic Markers for Chicken Fatty Liver

International Journal of Molecular Sciences ◽

10.3390/ijms21051800 ◽

2020 ◽

Vol 21 (5) ◽

pp. 1800

Author(s):

Xiaodong Tan ◽

Ranran Liu ◽

Siyuan Xing ◽

Yonghong Zhang ◽

Qinghe Li ◽

...

Keyword(s):

Fatty Liver ◽

Noncoding Rna ◽

Production Efficiency ◽

Target Genes ◽

Differentially Expressed ◽

Integrated Analysis ◽

Epigenetic Markers ◽

Differentially Methylated Genes ◽

Key Genes ◽

Immune Related Genes

Chickens are one of the most important sources of meat worldwide, and the occurrence of fatty liver syndrome (FLS) is closely related to production efficiency. However, the potential mechanism of FLS remains poorly understood. An integrated analysis of data from whole-genome bisulfite sequencing and long noncoding RNA (lncRNA) sequencing was conducted. A total of 1177 differentially expressed genes (DEGs) and 1442 differentially methylated genes (DMGs) were found. There were 72% of 83 lipid- and glucose-related genes upregulated; 81% of 150 immune-related genes were downregulated in fatty livers. Part of those genes was within differentially methylated regions (DMRs). Besides, sixty-seven lncRNAs were identified differentially expressed and divided into 13 clusters based on their expression pattern. Some lipid- and glucose-related lncRNAs (e.g., LNC_006756, LNC_012355, and LNC_005024) and immune-related lncRNAs (e.g., LNC_010111, LNC_010862, and LNC_001272) were found through a co-expression network and functional annotation. From the expression and epigenetic profiles, 23 target genes (e.g., HAO1, ABCD3, and BLMH) were found to be hub genes that were regulated by both methylation and lncRNAs. We have provided comprehensive epigenetic and transcriptomic profiles on FLS in chicken, and the identification of key genes and epigenetic markers will expand our understanding of the molecular mechanism of chicken FLS.

Download Full-text

lncRNA DLG1-AS1 Promotes Cell Proliferation by Competitively Binding with miR-107 and Up-Regulating ZHX1 Expression in Cervical Cancer

Cellular Physiology and Biochemistry ◽

10.1159/000493625 ◽

2018 ◽

Vol 49 (5) ◽

pp. 1792-1803 ◽

Cited By ~ 21

Author(s):

Xiaohui Rui ◽

Yun Xu ◽

Yaqing Huang ◽

Linjuan Ji ◽

Xiping Jiang

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Target Genes ◽

Cell Counting ◽

Cervical Cancer Cells ◽

A Cell ◽

Non Coding Rnas ◽

Biological Methods ◽

Cancer Tissues ◽

Competitive Endogenous Rna

Background/Aims: Recent studies have revealed that long non-coding RNAs (lncRNAs) are involved in the occurrence and development of various tumors, thereby attracting increasing attention from researchers. The important biological functions of lncRNAs have been recognized gradually, but their mechanism in cervical cancer remains unclear. Methods: Differentially expressed lncRNAs in cervical cancer and para-carcinoma tissues were identified by screening using an lncRNA array, and candidate lncRNAs were verified by quantitative real-time PCR. A series of bioinformatics and molecular biological methods were adopted to investigate the interactions among lncRNAs, microRNAs (miRNAs), and miRNA target genes in cervical cancer. Cell viability was measured using a Cell Counting Kit-8 assay. Results: DLG1-AS1 was the most significantly up-regulated lncRNA in cervical cancer tissues, and it was confirmed that cervical cancer patients with high DLG1-AS1 expression had a poor prognosis. Down-regulation of DLG1-AS1 expression suppressed the proliferation of cervical cancer cells. Further investigation revealed that DLG1-AS1 eliminated the inhibition of miR-107 on the expression of its target gene ZHX1 by competitively binding to miR-107. Moreover, rescue assays proved that the effect of DLG1-AS1 on the proliferation of cervical cancer cells was dependent on miR-107. Conclusion: DLG1-AS1/miR-107/ZHX1 can form a competitive endogenous RNA network that regulates the proliferation of cervical cancer cells, resulting in tumor progression.

Download Full-text

Telmisartan induces osteosarcoma cells growth inhibition and apoptosis via suppressing mTOR pathway

Open Life Sciences ◽

10.1515/biol-2018-0029 ◽

2018 ◽

Vol 13 (1) ◽

pp. 242-249 ◽

Cited By ~ 1

Author(s):

Chao Wang ◽

Wen-Bo Wang

Keyword(s):

Flow Cytometric Analysis ◽

Mtor Signaling ◽

Cell Counting ◽

Osteosarcoma Cell ◽

Osteosarcoma Cells ◽

Western Blot Assay ◽

Inhibition Of Proliferation ◽

Altered Expression ◽

Human Osteosarcoma Cells

AbstractOsteosarcoma (OS) is a commonly occurring primary malignant bone cancer with serious impact and high mortality, yet effective and safe therapy method not available. The aim of the present study was to elucidate the antitumor effect of telmisartan on human osteosarcoma cells in vitro and its underlying mechanism. The proliferation effect of osteosarcoma cell lines U2OS was examined by Cell Counting Kit-8. The invasive and migratory capabilities were determined by transwell invasion and migration assay. The percentage of apoptotic cells were detected by flow cytometric analysis and proteins related to apoptosis including Bax, Bcl-2 and Cleaved Caspase-3 were examined by western blotting. The expressions of mammalian target of rapamycin (mTOR) signaling relevant molecules were detected by western blot assay. Telmisartan treatment caused dose-dependent and time-dependent inhibition of proliferation and inducing anti-migration, anti-invasiveness and apoptosis of U2OS cells. The induction of apoptosis was confirmed concurring with the altered expression of proteins associated with the apoptosis. Mechanistically, telmisartan suppresses mTOR activation. Telmisartan can impede the growth, invasion, migration and induce the apoptosis of U2OS cell probably through inhibiting the mTOR signaling pathway activation. Thus, telmisartan is a potential drug for the prevention and treatment of human osteosarcomal cancer.

Download Full-text