scholarly journals Long Noncoding RNA HCG9 Promotes Osteosarcoma Progression through RAD51 by Acting as a ceRNA of miR-34b-3p

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Lu Wang ◽  
ShuangQing Li ◽  
Lin Qi ◽  
Lin Ling
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Noncoding Rna ◽  
Migration And Invasion ◽  
Mouse Tumor ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Qrt Pcr ◽  
Related Proteins

Background. Long noncoding RNAs (lncRNAs) have critical regulatory functions in biological and pathological activities during osteosarcoma progression. It is important to elucidate the expression pattern and reveal the underlying mechanisms of the newly identified lncRNAs. Methods. Herein, we screened the differentially expressed lncRNAs in osteosarcoma tumors and cell lines using lncRNA microarray. The candidate lncRNA was further verified by qRT-PCR, and the association of gene expression with clinicopathological features was evaluated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The targeting miRNA was identified using starBase analysis, and the competing endogenous RNA (ceRNA) network was established by STRING. Overexpression and silence of RNA were detected by qRT-PCR. Osteosarcoma cell proliferation was measured with CCK-8 assay, and the migration and invasion were evaluated with Transwell assay. Colony formation assay was observed. Flow cytometry evaluated the cell cycle. Western blot was performed to detect the mitotic markers and apoptosis-related proteins. A nude mouse tumor formation experiment was used to evaluate osteosarcoma progression in vivo. Cooverexpressing miR-34b-3p with RAD51 reversed the miR-34b-3p-induced changes in proliferation, the cell cycle, the expression of H2A.X, and that of apoptosis-related proteins. Results. HCG9 was identified as osteosarcoma-associated lncRNA. Osteosarcoma tissues and cell lines expressed higher levels of HCG9 as compared to normal tissues and osteoblasts, and high expression of HCG9 was further proved to be related to metastasis and the grade of osteosarcoma in clinical cases. Knockdown of HCG9 inhibited the proliferation, migration, and invasion of osteosarcoma cells. miR-34b-3p was identified as the target of HCG9, and RAD51 acted as a potential target of miR-34b-3p. Cooverexpressing miR-34b-3p with HCG9 partially suppressed the HCG9-stimulated proliferation, migration, and invasion of osteosarcoma cells in vitro and delayed the tumor progression in vivo. Conclusion. We discovered that lncRNA HCG9 promoted the proliferation of osteosarcoma cells via suppressing miR-34b-3p. Our study provides novel biomarkers and potential therapeutic targets for osteosarcoma treatment.

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.

MicroRNA-211-5p promotes apoptosis and inhibits the migration of osteosarcoma cells by targeting proline-rich protein PRR11

2020 ◽  
Vol 98 (2) ◽  
pp. 258-266 ◽  
Author(s):  
Dandan Song ◽  
Kun Yang ◽  
Wei Wang ◽  
Run Tian ◽  
Haoyu Wang ◽  
...  
Keyword(s):  
Young Adults ◽  
Survival Rate ◽  
Personalized Medicine ◽  
Cell Lines ◽  
Clinical Samples ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Expression Levels ◽  
Proline Rich Protein

Osteosarcoma remains fatal in adolescents and young adults, with a 5-year survival rate of less than 20%. However, the details for mechanisms that regulate osteosarcoma metastasis are poorly understood. We analyzed the expression levels of miR-211-5p in clinical samples of osteosarcoma as well as cell lines, and found that the expression of miR-211-5p was reduced in osteosarcoma. Moreover, induction of miR-211-5p in several osteosarcoma cell lines dramatically inhibited their migration and invasiveness. Furthermore, miR-211-5p overexpression led to a significant increase in the apoptosis of osteosarcoma cell. Importantly, our in vivo xenograft experiments showed that miR-211-5p strongly inhibits tumorigenesis. Additionally, functional experiments demonstrated that miR-211-5p suppresses the expression of proline-rich protein 11 (PRR11) by directly binding to the 3′ region of PRR11 mRNA. Moreover, we showed that PRR11 overexpression attenuated the increase of apoptosis and decreased migration and invasiveness when the upstream miR-211-5p was overexpressed. Our data provide new insights into the mechanisms that regulate osteosarcoma metastasis, and novel potential pharmaceutical targets for personalized medicine.

C/D-Box Snord105b Promotes Tumorigenesis in Gastric Cancer via ALDOA/C-Myc Pathway

2018 ◽  
Vol 45 (6) ◽  
pp. 2471-2482 ◽  
Author(s):  
Cong Zhang ◽  
Lian-mei Zhao ◽  
Hao Wu ◽  
Guo Tian ◽  
Su-li Dai ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Lines ◽  
Tumor Development ◽  
Migration And Invasion ◽  
Small Nucleolar Rnas ◽  
Wound Healing Assay ◽  
Qrt Pcr ◽  
New Biomarkers ◽  
Nucleolar Rnas

Background/Aims: Small nucleolar RNAs (snoRNAs) play an important role in carcinogenesis. In this study, we identified a C/D box snoRNA, snord105b, and further investigated the function and mechanism of the snord105b in gastric cancer (GC). Methods: The expression level of snord105b in GC tissures, sera and cell lines were detected by qRT-PCR. Cell viability was assessed using MTS assay. Transwell and wound healing assay were performed to evaluate migration and invasion, and protein expression was examined by western blotting. ChIRP and MS analysis was used to seek for the special binding protein of snord105b. Results: The snord105b was upregulated and associated with tumor size, differentiation, and pathological stage in GC. Snord105b affected proliferation, migration and invasion in multiple GC cell lines. The oncoqenic activity of snord105b was also confirmed with in vivo data. Mechanistically, snord105b specifically bound to ALDOA and affected C-myc, which plays a key role in carcinogenesis and tumor development. Conclusion: Snord105b appears to be a novel oncogene and is clinically and functionally involved in the development of GC. Targeting snord105b and its pathway may provide new biomarkers or potential treatments for patients with GC.

scholarly journals Armadillo Repeat-Containing Protein 8 (ARMC8) Silencing Inhibits Proliferation and Invasion in Osteosarcoma Cells

2016 ◽  
Vol 24 (5) ◽  
pp. 381-389 ◽  
Author(s):  
Feng Jiang ◽  
Yan Shi ◽  
Hong Lu ◽  
Guojun Li
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Underlying Mechanism ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Mesenchymal Transition ◽  
Armadillo Repeat ◽  
Proliferation And Invasion

Armadillo repeat-containing protein 8 (ARMC8) plays an important role in regulating cell migration, proliferation, tissue maintenance, signal transduction, and tumorigenesis. However, the expression pattern and role of ARMC8 in osteosarcoma are still unclear. In this study, our aims were to examine the effects of ARMC8 on osteosarcoma and to explore its underlying mechanism. Our results demonstrated that ARMC8 was overexpressed in osteosarcoma cell lines. Knockdown of ARMC8 significantly inhibited osteosarcoma cell proliferation in vitro and markedly inhibited xenograft tumor growth in vivo. ARMC8 silencing also suppressed the epithelial‐mesenchymal transition (EMT) phenotype, as well as inhibited the migration and invasion of osteosarcoma cells. Furthermore, knockdown of ARMC8 obviously inhibited the expression of β-catenin, c-Myc, and cyclin D1 in MG-63 cells. In conclusion, this report demonstrates that ARMC8 silencing inhibits proliferation and invasion of osteosarcoma cells. Therefore, ARMC8 may play an important role in the development and progression of human osteosarcoma and may represent a novel therapeutic target in the treatment of osteosarcoma.

scholarly journals LncRNA STK4 antisense RNA 1(STK4-AS1) affects the osteosarcoma cell cycle by regulating p53 protein

2021 ◽  
Author(s):  
Weitao Yao ◽  
Jingyu Hou ◽  
Guoqing Liu ◽  
Fangxing Wu ◽  
Qiang Yan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Cell Lines ◽  
P53 Protein ◽  
Mg63 Cell ◽  
Cyclin A ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
P53 Overexpression ◽  
Potential Biomarker

Abstract Background: LncRNA STK4-AS1 has been identified as a potential biomarker associated with multiple cancers. We proposed that STK4-AS1 plays a role in the proliferation of osteosarcoma by regulating its cell cycle. Methods: We compared the expression of STK4-AS1 in osteosarcoma vs normal samples both in clinical tissues and cell lines. We overexpressed and knockdown STK4-AS1 in p53 expressing osteosarcoma cells U2OS and p53 muted expressing osteosarcoma cells MG63 and analyzed cell viability and cell cycle. We overexpressed p53 in STK4-AS1 knockdown cells to explore the association of STK4-AS1 and p53 in the cell cycle. Results: The STK4-AS1 expression was higher in osteosarcoma tissue than adjacent normal bone tissues and was higher in osteosarcoma cell lines (U2OS, MG63, and SAOS-2) than in osteoblast cell lines (hFOB and HOB). Knockdown of STK4-AS1 in U2OS decreased the cell viability, increased cells in the G0/G1 phase, decreased cells in the S and G2/M phase, decreased expression of cyclin A and B, increased p53 and p21, and had no effect on cyclin D and cyclin E, while overexpression did the opposes. MG63 cell viability was not affected by altered STK4-AS1 levels. P53 overexpression in STK4-AS1 knockdown cells recovered cell viability, p21, cyclin A, and cyclin B expression. Conclusion: LncRNA STK4-AS1 affected p53 expressing osteosarcoma cells U2OS cell viability through regulating cell cycle, which is mediated by p53/p21 pathway.

scholarly journals LncRNA SNHG20 promotes migration and invasion of ovarian cancer via modulating the microRNA-148a/ROCK1 axis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qi Yang ◽  
Yu-Jie Dong
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Noncoding Rna ◽  
Tumor Xenograft ◽  
Migration And Invasion ◽  
Epithelial Cell Line ◽  
Invasion And Migration ◽  
And Migration

Abstract Background Ovarian cancer (OC) is characterized by early metastasis and poor prognosis, which threatens the health of women worldwide. Small nucleolar RNA host gene 20 (SNHG20), a long noncoding RNA (lncRNA), has been verified to be significantly up-regulated in several tumors, including OC. MicroRNA-148a (miR-148a)/rho-kinase1 (ROCK1) axis plays an important role in the modulation of tumor development. However, whether SNHG20 can regulate OC progression through miR-148a/ROCK1 axis remains unclear. Normal human ovarian epithelial cell line and four OC cell lines were adopted for in vitro experiments. Real-time PCR was performed to assess the levels of SNHG20 and miR-148a. OC cell proliferation, apoptosis, invasion and migration were detected using clone formation, flow cytometry, transwell, and wound healing assays, respectively. Tumor xenograft assay was applied to evaluate the effect of SNHG20 on tumor growth in vivo. Results Significant higher expression of SNHG20 was observed in OC cell lines. SNHG20 markedly promoted the invasion, migration, proliferation and inhibited the apoptosis of OC cells. SNHG20 enhanced ROCK1 expression by sponging miR-148a, and the direct binding between SNHG20/ROCK1 and miR-148a was identified. Conclusion SNHG20 promoted invasion and migration of OC via targeting miR-148a/ROCK1 axis. The present research may provide a novel insight for the therapeutic strategies of OC.

scholarly journals Long Noncoding RNA LINC01133 Promotes the Malignant Behaviors of Renal Cell Carcinoma by Regulating the miR-30b-5p/Rab3D Axis

2020 ◽  
Vol 29 ◽  
pp. 096368972096441
Author(s):  
Xiaoqiang Zhai ◽  
Yan Wu ◽  
Zhenlong Wang ◽  
Dawei Zhao ◽  
Hecheng li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Long Noncoding Rna ◽  
Renal Cell ◽  
Noncoding Rna ◽  
Polymerase Chain Reaction Analysis ◽  
Migration And Invasion ◽  
Tissue Specimens

Renal cell carcinoma (RCC) is the most common type of kidney cancer with rising incidence. Long noncoding RNA (lncRNA) LINC01133 is a novel lncRNA that is involved in the development of several types of cancers. However, the role of LINC01133 in RCC has not been reported. Thus, in this study, we investigated the functions of LINC01133 in RCC. The qualitative real-time polymerase chain reaction analysis was performed to examine the levels of LINC01133 in RCC tissues and adjacent tissues, as well as RCC cell lines. The results showed that LINC01133 was highly expressed in RCC tissue specimens and cell lines. Downregulation of LINC01133 significantly inhibited the proliferation, migration, and invasion of RCC cells. Further mechanistic investigations proved that LINC01133 directly interacted with microRNA (miR)-30b-5p and regulated the miR-30b-5p expression in RCC cell lines. Moreover, miR-30b-5p exhibited tumor-suppressive activity in RCC cell lines, which was mediated by targeting Ras-related protein Rab-3D (Rab3D). In vivo study showed that LINC01133 knockdown suppressed tumor growth in the nude mice. Taken together, these findings indicated that LINC01133 might be an oncogene in RCC through regulation of the miR-30b-5p/Rab3D axis. Thus, LINC01133 might serve as a potential therapeutic target for the treatment of RCC.

scholarly journals Osthole Induces Cell Cycle Arrest and Inhibits Migration and Invasion via PTEN/Akt Pathways in Osteosarcoma

2016 ◽  
Vol 38 (6) ◽  
pp. 2173-2182 ◽  
Author(s):  
Lu Wang ◽  
Lei Yang ◽  
Ying Lu ◽  
Yingzhun Chen ◽  
Tianhua Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Molecular Mechanisms ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Dependent Manner ◽  
Signaling Mechanism ◽  
Inhibition Of Proliferation

Background/Aims: Osteosarcoma is the second highest cause of cancer-related death in children and adolescents. Majority of osteosarcoma patients (90%) show metastasis. Previous reports revealed that osthole showed antitumor activities via induction of apoptosis and inhibition of proliferation. However, the potential effects and detailed molecular mechanisms involved remained unclear. Methods: Cell viability was analyzed by MTT assay in osteosarcoma cell lines MG-63 and SAOS-2. Cell cycle was detected by flow cytometry. The effects of migration and invasion were evaluated by wound healing assay and transwell assays. Moreover, the level of proteins expression was determined by Western blot. Results: The cell viability of MG63 and SAOS-2 were markedly inhibited by osthole in a dose- and time-dependent manner. Cell cycle was arrested and the ability of migration and invasion was obviously reduced when cells were exposed to osthole. Moreover, enzymes involved in PTEN/Akt pathway were regulated such as PTEN and p-Akt proteins. Furthermore, osthole inhibited the tumor growth in vivo. Conclusion: Our study unraveled, for the first time, the ability of osthole to suppress osteosarcoma and elucidated the regulation of PTEN/Akt pathway as a signaling mechanism for the anti-tumor action of osthole. These findings indicate that osthole may represent a novel therapeutic strategy in the treatment of osteosarcoma.

scholarly journals LncRNA RNCR3 Promotes the Progression of HCC by Activating the Akt/GSK3β Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Qi Xie ◽  
Tongfa Ju ◽  
Chunhua Zhou ◽  
Lulu Zhai ◽  
Ho Lin
Keyword(s):  
Signaling Pathway ◽  
Noncoding Rna ◽  
Migration And Invasion ◽  
Promote Cell Proliferation ◽  
Qrt Pcr ◽  
In Vivo Experiments ◽  
Tumor Number ◽  
Tumor Growth And Metastasis

Objective. To explore the potential biological roles of long noncoding RNA (lncRNA) RNCR3 in human hepatocellular carcinoma (HCC). Methods. First, the expression of RNCR3 was detected by qRT-PCR. Then, in vitro experiments were performed to investigate the effects of RNCR3 on the proliferation, cell cycle, migration, and invasion of HCC cells, while the effects of RNCR3 on HCC tumor growth and metastasis were investigated using in vivo experiments. Finally, western blot was used to study the activation of the Akt/GSK3β signaling pathway. Results. RNCR3 was highly expressed in both HCC tissues and cells, and the expression of RNCR3 was closely related to tumor size, tumor number, TNM stage, and overall survival time. In vitro, RNCR3 served as an oncogene to promote cell proliferation, migration, and invasion, and in vivo, RNCR3 promoted the growth and metastasis of HCC tumors. In terms of mechanism, RNCR3 induced the phosphorylation of Akt (thr308 and ser473) and GSK3β (ser9) but decreased the expression of GSK3β, which activated the Akt/GSK3β signaling pathway. Conclusion. The high expression of lncRNA RNCR3 in HCC can promote the proliferation, migration, invasion, growth, and metastasis of HCC by activating the NF-κB signaling pathway.

scholarly journals AdipoRon Affects Cell Cycle Progression and Inhibits Proliferation in Human Osteosarcoma Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Luigi Sapio ◽  
Ersilia Nigro ◽  
Angela Ragone ◽  
Alessia Salzillo ◽  
Michela Illiano ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Lines ◽  
Molecular Mechanisms ◽  
Childhood And Adolescence ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Antitumor Effects ◽  
Human Osteosarcoma Cells ◽  
U2os Cells ◽  
The Impact

AdipoRon (AdipoR) is the first synthetic molecule acting as a selective and potent adiponectin receptor agonist. Recently, the possible pharmacological use of AdipoR in different pathological conditions has been addressed. Interestingly, initial evidence suggests that AdipoR may have anticancer properties in different preclinical models, such as pancreatic and ovarian cancer. To our knowledge, so far no research has been directed at determining the impact of AdipoR on osteosarcoma, the most aggressive and metastatic bone malignancy occurring in childhood and adolescence age. Here, we investigate the possible antitumor effects of AdipoR in osteosarcoma cell lines. MTT and cell growth curve assays clearly indicate that AdipoR inhibits, at different extents, proliferation in both U2OS and Saos-2 osteosarcoma cell lines, the latter being more sensitive. Moreover, flow cytometry-based assays point out a significant G0/G1 phase accumulation and a contemporary S phase decrease in response to AdipoR. Consistent with the different sensitivity, a strong subG1 appearance in Saos-2 after 48 and 72 hours of treatment is also observed. The investigation of the molecular mechanisms highlights a common and initial ERK1/2 activation in response to AdipoR in both Saos-2 and U2OS cells. Interestingly, a simultaneous and dramatic downregulation of p70S6K phosphorylation, one of the main targets of mTORC1 pathway, has also been observed in AdipoR-treated Saos-2, but not in U2OS cells. Importantly, a strengthening of AdipoR-induced effects was reported upon everolimus-mediated mTORC1 perturbation in U2OS cells. In conclusion, our findings provide initial evidence of AdipoR as an anticancer molecule differently affecting various signaling pathways involved in cell cycle and cell death in osteosarcoma cells and encourage the design of future studies to further understand its pattern of activities.

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