scholarly journals MicroRNA-133a Inhibits Osteosarcoma Cells Proliferation and Invasion via Targeting IGF-1R

2016 ◽  
Vol 38 (2) ◽  
pp. 598-608 ◽  
Author(s):  
Guangnan Chen ◽  
Tingting Fang ◽  
Zhongming Huang ◽  
Yiying Qi ◽  
Shaohua Du ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Luciferase Reporter ◽  
Osteoblastic Cell ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Invasion And Metastasis ◽  
Osteoblastic Cell Line ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cell

Background/Aims: MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. Downregulated microRNAs and their roles in cancer development have attracted much attention. A growing body of evidence showed that microRNA-133a (miR-133a) has inhibitory effects on cell proliferation, migration, invasion, and metastasis of osteosarcoma. Methods: MiR-133a expression in human osteosarcoma cell lines and human normal osteoblastic cell line hFOB was investigated by real-time PCR (RT-PCR). The role of miR-133a in human osteosarcoma growth and invasion was assessed in cell lines in vitro and in vivo. Then, luciferase reporter assay validated IGF-1R as a downstream and functional target of miR-133a, and functional studies revealed that the anti-tumor effect of miR-133a was probably due to targeting and repressing of IGF-1R expression. Results: MiR-133a was lower expressed in human osteosarcoma cell lines than human normal osteoblastic cell line hFOB and its effect on inhibiting proliferation, invasion and metastasis is mediated by its direct interaction with the IGF-1R. Furthermore, the tumour-suppressive function of miR-133a probably contributed to inhibiting the activation AKT and ERK signaling pathway. Conclusion: MiR-133a suppresses osteosarcoma progression and metastasis by targeting IGF-1R in human osteosarcoma cells, providing a novel candidate prognostic factor and a potential anti-metastasis therapeutic target in osteosarcoma.

scholarly journals Antiproliferative Properties of Oleuropein in Human Osteosarcoma Cells

2016 ◽  
Vol 11 (4) ◽  
pp. 1934578X1601100 ◽  
Author(s):  
Jose M. Moran ◽  
Olga Leal-Hernandez ◽  
Maria L. Canal-Macías ◽  
Raul Roncero-Martin ◽  
Rafael Guerrero-Bonmatty ◽  
...  
Keyword(s):  
Cell Lines ◽  
Osteosarcoma Cell ◽  
Dependent Manner ◽  
Osteosarcoma Cells ◽  
Probit Regression ◽  
Cytotoxic Effects ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
Mg63 Cells ◽  
Human Osteosarcoma Cell

In this study, we evaluated the antiproliferative activity on two human osteosarcoma cell lines (MG-63 and Saos2) of oleuropein, an olive oil compound traditionally found in the Mediterranean diet. Oleuropein exhibited obvious cytotoxic effects on human osteosarcoma cells in a concentration- and time-dependent manner. Statistical analysis of IC50 by the Probit regression method suggested that oleuropein had similar toxic effects on both cell lines tested (IC50 range from 247.4–475.0 μM for MG63 cells and from 798.7–359.9 μM for Saos2 cells).

scholarly journals Elevated expression of serine/threonine phosphatase type 5 correlates with malignant proliferation in human osteosarcoma.

1970 ◽  
Vol 64 (1) ◽  
Author(s):  
Kun Han ◽  
Zhihua Gan ◽  
Shuchen Lin ◽  
Haiyan Hu ◽  
Zan Shen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Functional Role ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Facs Analysis ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cell ◽  
Elevated Expression ◽  
Common Primary Malignant Bone

Osteosarcoma is the most common primary malignant bone tumor in adolescents and young adults. However, the involvement of serine/threonine phosphatase type 5 (PP5) in osteosarcoma remains unclear. The aim of this study was to evaluate the functional role of PP5 in osteosarcoma cells. Firstly, we found that PP5 is widely expressed in several human osteosarcoma cell lines. Then we used lentivirus-delivered siRNA to silence PP5 expression in Saos-2 and U2OS cell lines. Knockdown of endogenous PP5 expression by shRNA-expressing lentivirus significantly decreased the viability and proliferation of the osteosarcoma cells. Moreover, FACS analysis showed that knockdown of PP5 expression induced a significant arrest in the G0/G1 phase of the cell cycle, which was associated with the inhibition of cell proliferation. Therefore, knockdown of PP5 is likely to provide a novel alternative to targeted therapy of osteosarcoma and deserves further investigation.

scholarly journals Effect of the Tumor Suppressor miR-320a on Viability and Functionality of Human Osteosarcoma Cell Lines Compared to Primary Osteoblasts

2020 ◽  
Vol 10 (8) ◽  
pp. 2852
Author(s):  
Laura De-Ugarte ◽  
Susanna Balcells ◽  
Robert Guerri-Fernandez ◽  
Daniel Grinberg ◽  
Adolfo Diez-Perez ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Tumor Suppressor ◽  
Cell Viability ◽  
Cell Lines ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Matrix Mineralization ◽  
Cellular Effects ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cell

The miR-320a regulates a number of genes involved in various physiological processes. In particular, it has been reported as a tumor suppressor in several types of human cancers and involved in osteoporotic fracture and osteoblast function. Hence, the role of miR-320a has been evaluated in tumor cells and in primary cells in a separated context, but its effect has never been explored in a comparative manner. The present study aims to evaluate the cellular effects of miR-320a on human osteosarcoma cell lines (MG-63 and U2OS) compared to that on primary human osteoblasts (hOBs). miR-320a was either overexpressed or inhibited in all cell lines, and cell proliferation and viability were analyzed. Additionally, the effects of miR-320a on matrix mineralization, alkaline phosphatase activity, and oxidative stress were also evaluated in order to assess osteoblast functionality. In osteosarcoma cells, miR-320a overexpression reduced cell viability and proliferation, while in hOB cell viability was not affected and proliferation even was increased. The overexpression of miR-320a in both osteosarcoma cells and hOBs reduced the mineralization capacity. Finally, an increased oxidative stress was detected in all cells after miR-320a overexpression mainly in osteosarcoma. In conclusion, the overexpression of miR-320a increased stress oxidation levels, which could be involved in the reduced osteoblast performance, even though the cell viability was only affected in osteosarcoma cells.

scholarly journals The proliferation and invasion of osteosarcoma are inhibited by miR-101 via targetting ZEB2

2019 ◽  
Vol 39 (2) ◽  
Author(s):  
Haopeng Lin ◽  
Xiaodong Zheng ◽  
Ting Lu ◽  
Yang Gu ◽  
Canhao Zheng ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Bone Cell ◽  
Luciferase Reporter ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Direct Target ◽  
Proliferation And Invasion

AbstractHaving a better grasp of the molecular mechanisms underlying carcinogenesis and progression in osteosarcoma would be helpful to find novel therapeutic targets. Different types of cancers have presented abnormal expression of miRNA-101 (miR-101). Nevertheless, we still could not figure out what expression of miR-101 in human osteosarcoma is and its biological function. Thus, we conducted the present study to identify its expression, function, and molecular mechanism in osteosarcoma. We detected the expression of miR-101 in osteosarcoma samples and cell lines. The effects of miR-101 on osteosarcoma cells’ proliferation and invasion were evaluated. Luciferase reporter assay was applied to identify the direct target of miR-101. Compared with adjacent normal specimens and normal bone cell line by using qPCR, the expression levels of miR-101 in osteosarcoma specimens and human osteosarcoma cell lines distinctly decreased. According to function assays, we found that overexpression of miR-101 significantly inhibited the cell proliferation and invasion in osteosarcoma cells. Moreover, we confirmed that zinc finger E-box binding homeobox 2 (ZEB2) was a direct target of miR-101. In addition, overexpression of ZEB2 could rescue the inhibition effect of proliferation and invasion induced by miR-101 in osteosarcoma cells. MiR-101 has been proved to be down-regulated in osteosarcoma and has the ability to suppress osteosarcoma cell proliferation and invasion by directly targetting ZEB2.

Sex Determining Region Y-Box 12 Promotes Proliferation, Migration and Invasion of Osteosarcoma Cells by Activating β-Catenin/T Cell Factor Axis

2021 ◽  
Vol 11 (11) ◽  
pp. 2225-2231
Author(s):  
Minhua Lu ◽  
Xingguang Chen
Keyword(s):  
Cell Lines ◽  
Critical Role ◽  
Migration And Invasion ◽  
Osteoblastic Cell ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Western Blot Assay ◽  
Osteoblastic Cell Line ◽  
Well Assay ◽  
And Migration

Objectives: This study aims to clarify the role of sex determining region Y-box 12 (SOX12) in accelerating the proliferative, migratory and invasive abilities of osteosarcoma (OS) via β-catenin/TCF axis. Materials and Methods: SOX12 levels in human osteosarcoma cell lines and human fetal osteoblastic cell line were determined by RT-qPCR. The proliferation rates of osteosarcoma cells were both determined by CCK-8 assay and EdU staining. In addition, osteosarcoma cell migration and migration were determined by wound healing assay and trans-well assay, respectively. TOPFlash/FOPFlash reporter activity assay and western blot assay were simultaneously performed for the detection of β-catenin/TCF axis. Results: SOX12 was elevated in osteosarcoma cell lines, developing the critical role in proliferation, migration and invasion of osteosarcoma cells. The β-catenin/TCF pathway was activated in osteosarcoma. SOX12 overexpression exerted promotive effects on activation of β-catenin/TCF pathway and SOX12 knockdown showed the opposite effects. Conclusions: SOX12 accelerates proliferation, migration and invasion of osteosarcoma cells by activating β-catenin/TCF axis, thus stimulating the progression of OS.

scholarly journals Anti-Metastatic and Anti-Angiogenic Effects of Curcumin Analog DK1 on Human Osteosarcoma Cells In Vitro

2021 ◽  
Vol 14 (6) ◽  
pp. 532
Author(s):  
Muhammad Nazirul Mubin Aziz ◽  
Nurul Fattin Che Rahim ◽  
Yazmin Hussin ◽  
Swee Keong Yeap ◽  
Mas Jaffri Masarudin ◽  
...  
Keyword(s):  
Cell Lines ◽  
Safety Profile ◽  
Quantitative Polymerase Chain Reaction ◽  
Tube Formation ◽  
Osteosarcoma Cell ◽  
Curcumin Analog ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
Human Osteosarcoma Cell

Osteosarcoma (OS) is a life-threatening malignant bone tumor associated with poor prognosis among children. The survival rate of the patient is still arguably low even with intensive treatment provided, plus with the inherent side effects from the chemotherapy, which gives more unfavorable outcomes. Hence, the search for potent anti-osteosarcoma agent with promising safety profile is still on going. Natural occurring substance like curcumin has gained a lot of attention due to its splendid safety profile as well as it pharmacological advantages such as anti-metastasis and anti-angiogenesis. However, natural curcumin was widely known for its poor cellular uptake, which undermines all potential that it possesses. This prompted the development of synthetically synthesized curcuminoid analog, known as (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2- en-1-one (DK1). In this present study, in vitro scratch assay, transwell migration/invasion assay, HUVEC tube formation assay, and ex vivo rat aortic ring assays were performed in order to investigate the anti-metastatic and anti-angiogenic potential of DK1. For further comprehension of DK1 mechanism on human osteosarcoma cell lines, microarray gene expression analysis, quantitative polymerase chain reaction (qPCR), and proteome profiler were adopted, providing valuable forecast from the expression of important genes and proteins related to metastasis and angiogenesis. Based on the data gathered from the bioassays, DK1 was able to inhibit the metastasis and angiogenesis of human osteosarcoma cell lines by significantly reducing the cell motility, number of migrated and invaded cells as well as the tube formation and micro-vessels sprouting. Additionally, DK1 also has significantly regulated several cancer pathways involved in OS proliferation, metastasis, and angiogenesis such as PI3K/Akt and NF-κB in both U-2 OS and MG-63. Regulation of PI3K/Akt caused up-regulation of genes related to metastasis inhibition, namely, PTEN, FOXO, PLK3, and GADD45A. Meanwhile, NF-κB pathway was regulated by mitigating the expression of NF-κB activator such as IKBKB and IKBKE in MG-63, whilst up-regulating the expression of NF-κB inhibitors such as NFKBIA and NFKBIE in U-2 OS. Finally, DK1 also has successfully hindered the metastatic and angiogenic capability of OS cell lines by down-regulating the expression of pro-metastatic genes and proteins like MMP3, COL11A1, FGF1, Endoglin, uPA, and IGFBP2 in U-2 OS. Whilst for MG-63, the significantly down-regulated oncogenes were Serpin E1, AKT2, VEGF, uPA, PD-ECGF, and Endoglin. These results suggest that curcumin analog DK1 may serve as a potential new anti-osteosarcoma agent due to its anti-metastatic and anti-angiogenic attributes.

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

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.

scholarly journals Establishment and characterization of human osteosarcoma cell lines with different pulmonary metastatic potentials

2009 ◽  
Vol 61 (1-2) ◽  
pp. 37-44 ◽  
Author(s):  
Xiang Chen ◽  
Tong-Tao Yang ◽  
Wei Wang ◽  
Hong-Hui Sun ◽  
Bao-An Ma ◽  
...  
Keyword(s):  
Cell Lines ◽  
Osteosarcoma Cell ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cell

scholarly journals Rhotekin 2 silencing inhibits proliferation and induces apoptosis in human osteosarcoma cells

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Xiong Wang ◽  
Lei Zhang ◽  
Wenji Wang ◽  
Yuchen Wang ◽  
Ye Chen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Phase Cell ◽  
Osteosarcoma Cell ◽  
Cyclin Dependent Kinase ◽  
Potential Therapeutic Target ◽  
Human Osteosarcoma ◽  
Cycle Arrest ◽  
Human Osteosarcoma Cells ◽  
Human Osteosarcoma Cell ◽  
Induced Apoptosis

Human osteosarcoma is the most frequent primary malignant of bone, and often occurs in adolescents. However, molecular mechanism of this disease remains unclear. In the present study, we found that the level of Rhotekin 2 (RTKN2) was up-regulated in osteosarcoma tissues and cell lines. In addition, silencing of RTKN2 of human osteosarcoma cell lines U2OS, inhibited proliferation, and induced G1 phase cell cycle arrest via reducing the level of the cyclin-dependent kinase 2 (CDK2). Furthermore, RTKN2 knockdown in the U2OS cells induced apoptosis by increasing the level of Bax and decreasing the level of Bcl2. These results suggested that RTKN2 is involved in the progression of human osteosarcoma, and may be a potential therapeutic target.

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