scholarly journals Rho-GEF Trio regulates osteosarcoma progression and osteogenic differentiation through Rac1 and RhoA

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Junyi Wang ◽  
Lichan Yuan ◽  
Xiaohong Xu ◽  
Zhongyin Zhang ◽  
Yuhuan Ma ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Migration And Invasion ◽  
Osteosarcoma Cells ◽  
Primary Bone Tumor ◽  
Normal Tissues ◽  
Primary Bone ◽  
Metastasis Rate ◽  
Rho Gef

AbstractOsteosarcoma (OS) is the most common primary bone tumor. Its high mortality rate and metastasis rate seriously threaten human health. Currently, the treatment has reached a plateau, hence we urgently need to explore new therapeutic directions. In this paper, we found that Trio was highly expressed in osteosarcoma than normal tissues and promoted the proliferation, migration, and invasion of osteosarcoma cells. Furthermore, Trio inhibited osteosarcoma cells’ osteogenic differentiation in vitro and accelerated the growth of osteosarcoma in vivo. Given Trio contains two GEF domains, which have been reported as the regulators of RhoGTPases, we further discovered that Trio could regulate osteosarcoma progression and osteogenic differentiation through activating RhoGTPases. In summary, all our preliminary results showed that Trio could be a potential target and prognostic marker of osteosarcoma.

scholarly journals circLMTK2 acts as a sponge of miR-150-5p and promotes proliferation and metastasis in gastric cancer

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Sen Wang ◽  
Dong Tang ◽  
Wei Wang ◽  
Yining Yang ◽  
Xiaoqing Wu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Bioinformatic Analysis ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Normal Tissues ◽  
Tumour Metastasis ◽  
Genome Wide ◽  
Proliferation And Metastasis

Abstract Background As a novel class of non-coding RNAs, circular RNAs (circRNAs) are key regulators of the development and progression of different cancers. However, little is known about the function and biological mechanism of circLMTK2, also named hsa_circ_0001725, in gastric cancer (GC) tumourigenesis. Methods circLMTK2 was identified in ten paired cancer specimens and adjacent normal tissues by RNA sequencing and genome-wide bioinformatic analysis and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of circLMTK2 combined with in vitro and in vivo assays were performed to prove the functional significance of circLMTK2. The molecular mechanism of circLMTK2 was demonstrated by searching the CircNet database and confirmed by RNA in vivo precipitation assays, western blotting, luciferase assays and rescue experiments. Results circLMTK2 was frequently upregulated in GC tissues, and high circLMTK2 expression was associated with poor prognosis, lymph node metastasis and poor TNM stage in GC patients. Functionally, circLMTK2 overexpression promoted GC cell proliferation and tumourigenicity in vitro and in vivo. Furthermore, ectopic circLMTK2 expression enhanced GC cell migration and invasion in vitro and tumour metastasis in vivo. In addition, we demonstrated that circLMTK2 could sponge miR-150-5p, thus indirectly regulating the c-Myc expression and contributing to GC tumourigenesis. Conclusion Our findings demonstrate that circLMTK2 functions as a tumour promoter in GC through the miR-150-5p/c-Myc axis and could thus be a prognostic predictor and therapeutic target for GC.

scholarly journals Upregulated TRIM11 Exerts its Oncogenic Effects in Hepatocellular Carcinoma Through Inhibition of P53

2017 ◽  
Vol 44 (1) ◽  
pp. 255-266 ◽  
Author(s):  
Jinjin Liu ◽  
Jun Rao ◽  
Xuming Lou ◽  
Jian Zhai ◽  
Zhenhua Ni ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Development ◽  
Tumor Model ◽  
Migration And Invasion ◽  
P53 Expression ◽  
Protein Levels ◽  
Normal Tissues ◽  
P53 Signaling

Background/Aims: The tripartite motif containing (TRIM) family plays crucial roles in tumor development and progression. However, little is known about the function and mechanism of TRIM11 in hepatocellular carcinoma (HCC). Methods: The expression levels of TRIM11 were examined by real-time PCR, Western blot and Immunohistochemical (IHC) staining. TRIM11 knockdown cells were produced by lentivirus infection, and functional assays, such as MTT, colony formation assay, migration and invasion assays and a xenograft tumor model were used to investigate the role of TRIM11 in HCC. We also determined the effect of TRIM11 on p53 signaling and its downstream molecules. Results: We found that TRIM11 mRNA and protein levels were significantly increased in HCC tissues as compared with normal tissues; increased levels correlated with poor patient survival. By loss- and gain-of-function investigations, knockdown of TRIM11 suppressed cell proliferation, migration, invasion in vitro and tumor growth in vivo. Moreover, TRIM11 negatively regulated p53 expression. Knockdown of p53 abrogated the in vitro and in vivo biological functions of TRIM11 shRNA in HCC cells. Conclusions: These data show that TRIM11 exerts its oncogenic effect in HCC by downregulating p53 both in vitro and in vivo. Our data provide new insights into the pathogenesis of HCC and indicate that TRIM11 may serve as a new therapeutic target for HCC treatment.

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 Evaluation of Two Novel Therapeutics Against Human and Canine Osteosarcoma

2020 ◽  
Author(s):  
Heather Wilson-Robles ◽  
Tasha Miller ◽  
Chao Sima ◽  
Jianping Hua ◽  
Milana Cypert ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Xenograft Model ◽  
Western Blots ◽  
Primary Bone Tumor ◽  
Murine Xenograft Model ◽  
Primary Bone ◽  
Number Of Cells

Abstract Background: Osteosarcoma (OS) is the most common primary bone tumor in both humans and canines. This tumor has an aggressive course leading to the development of metastatic lesions in most patients diagnosed with this disease. Two new novel agents, MLN9708 and SH4-54, work as a proteasome inhibitor and a STAT3 inhibitor, respectively. Targets of these drugs have been shown to be overexpressed in OS in both species. Methods: Two human and two canine OS cell lines were exposed in vitro to both drugs alone and in combination. The number of cells undergoing apoptosis, as well as the number of cells capable of invasion through a matrigel basement membrane was evaluated after exposure to the drugs. Additionally, PCR and Western blots of downstream targets were evaluated. Finally, both drugs were tested against each cell line in an in vivo murine xenograft model. Results: All four cell lines were sensitive to MLN9708, one of the human cell lines and both canine cell lines were resistant to SH4-54. MLN9708 was also better at inhibiting invasion in three of the four cell lines. In the murine xenografts MLN9708 inhibited growth and metastasis in 143B (human OS) and the combination inhibited growth in the canine OS cell line (MCKOS). Conclusions: Though SH4-54 demonstrated robust cell killing in 143B in vitro, MLN9708 demonstrated broader activity across species for the treatment of OS. Further investigation into this drug is warranted as a treatment for OS. Combination of this drug with a STAT3 inhibitor may be worthwhile in canine OS.

scholarly journals Circular RNA _0008278 acts as a sponge of miR-378 and promotes proliferation and metastasis in gastric cancer

2021 ◽  
Author(s):  
Xuan Li ◽  
Haisheng Qian ◽  
Hao Dong ◽  
Yini Dang ◽  
Lei Peng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Bioinformatic Analysis ◽  
Potential Method ◽  
Circular Rna ◽  
Migration And Invasion ◽  
Normal Tissues ◽  
Tumour Metastasis ◽  
Regulatory Molecule

Abstract Background: Circular RNA (circRNA) is rising as an indispensable regulatory molecule in the progression of various kinds of malignant growth. However, little is known about the capacity and instruments of circRNA_0008727 in gastric cancer (GC). Our point was to recognize a novel circRNA-microRNA-mRNA useful system in gastric cancer. Method: CircRNA_0008278 was identified in three paired cancer specimens and adjacent normal tissues by RNA sequencing and genome-wide bioinformatic analysis and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of circRNA_0008278 combined with in vitro and in vivo assays were performed to prove the functional significance of circRNA_0008278. The molecular mechanism of circRNA_0008278 was demonstrated by searching the CircNet database and confirmed by RNA in vivo precipitation assays, western blotting, luciferase assays and rescue experiments.Results: CircRNA_0008278 was frequently upregulated in GC tissues, and high circRNA_0008278 expression was associated with poor prognosis, lymph node metastasis and poor TNM stage in GC patients. Functionally, circRNA_0008278 overexpression promoted GC cell proliferation and tumourigenicity in vitro and in vivo. Furthermore, circRNA_0008278 over-expression enhanced GC cell migration and invasion in vitro and tumour metastasis in vivo. In addition, we demonstrated that circRNA_0008278 could sponge miR-378, thus indirectly regulating theYY1 expression and contributing to GC tumourigenesis.Conclusion: Our findings demonstrate that circRNA_0008278 functions as a tumour promoter in GC, and a new pathway circRNA_0008278/miR-378/YY1 which may be potential method for gastric cancer treatment.

scholarly journals SLC25A21 Suppresses Cell Growth in Bladder Cancer Via The Reactive Oxygen Species-Mediated Mitochondrion-Dependent Apoptosis Pathway

2021 ◽  
Author(s):  
Yong Wang ◽  
Jiawen Gao ◽  
Shasha Hu ◽  
Weiting Zeng ◽  
Hongjun Yang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Treatment Strategies ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Apoptosis Pathway ◽  
Normal Tissues ◽  
Induced Apoptosis ◽  
New Diagnosis

Abstract Background: Bladder cancer (BCa) is a commonly diagnosed malignancy worldwide that has poor survival depending on its intrinsic biologic aggressiveness and a peculiar radio- and chemoresistance features. Gaining a better understanding of tumorigenesis and developing new diagnosis and treatment strategies for BCa is important for improving BCa clinical outcome. SLC25 family member 21 (SLC25A21), a carrier transporting C5-C7 oxodicarboxylates, has been reported to contribute to oxoadipate acidemia. However, the potential role of SLC25A21 in cancer remains absolutely unknown. Methods: The expression levels of SLC25A21 in BCa and normal tissues were examined by real-time PCR and immunohistochemistry. Gain-of- and loss-of-function experiments were performed to detect the biological functions of SLC25A21 in vitro and in vivo by CCK-8 assay, plate colony formation assay, cell migration, invasion assay and experimental animal models. The subcellular distribution of substrate mediated by SLC25A21, mitochondrial membrane potential and ROS production were assessed to explore the potential mechanism of SLC25A21 in BCa.Results: We found that the expression of SLC25A21 was downregulated in BCa tissues compared to normal tissues. A significant positive correlation between decreased SLC25A21 expression and poor prognosis was observed in BCa patients. Overexpression of SLC25A21 significantly inhibited cell proliferation, migration and invasion and induced apoptosis in vitro. Moreover, the enhanced SLC25A21 expression significantly suppressed tumor growth in a xenograft mouse model. Furthermore, we revealed that SLC25A21 suppressed BCa growth by inducing the efflux of mitochondrial α-KG to the cytosol, decreasing to against oxidative stress, and activating the ROS-mediated mitochondrion-dependent apoptosis pathway. Conclusions: Our findings provide the first link between SLC25A21 expression and BCa and demonstrate that SLC25A21 acts as a crucial suppressor in BCa progression, which may help to provide new targets for BCa intervention.

scholarly journals Osteosarcoma-Derived Small Extracellular Vesicles Enhance Tumor Metastasis and Suppress Osteoclastogenesis by miR-146a-5p

2021 ◽  
Vol 11 ◽  
Author(s):  
Yoshihiro Araki ◽  
Hisaki Aiba ◽  
Takeshi Yoshida ◽  
Norio Yamamoto ◽  
Katsuhiro Hayashi ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Tumor Metastasis ◽  
Early Stage ◽  
Orthotopic Implantation ◽  
Optimal Care ◽  
Primary Bone Tumor ◽  
Biopsy Specimens ◽  
Primary Bone

Osteosarcoma is the most frequent type of primary bone tumor in children and adolescents, thus care for patients with malignant osteosarcoma is strongly required. The roles of small extracellular vesicles (SEVs) in enhancing metastases have been demonstrated in multiple tumors, but they are still poorly understood in osteosarcoma. Hence, this study investigated the effects of SEVs on progression and the tumor microenvironment in mice and patients. In an orthotopic implantation study, we found that osteosarcoma-derived SEVs had the potential to enhance metastases and angiogenesis. In addition, osteosarcoma-derived SEVs decreased the number of mature osteoclasts in vivo. In vitro osteoclastogenesis studies revealed that the inhibition of osteoclast maturation by osteosarcoma-derived SEVs was mediated by suppressing the NF-κB signal pathway. MicroRNA analysis of SEVs from different malignant human osteosarcomas revealed that miR-146a-5p was involved in the inhibition of osteoclastogenesis. In osteosarcoma patients, lower numbers of osteoclasts in biopsy specimens at the first visits were correlated with higher malignancy. These findings indicated that osteosarcoma-derived SEVs enhance distant metastasis of osteosarcomas by inhibiting osteoclast maturation, which may be a useful prognostic marker. This diagnostic method may enable to predict malignancy at early stage, and help to provide optimal care to patients with risk of high malignancy.

scholarly journals LncRNA LEF1-AS1 promotes metastasis of prostatic carcinoma via the Wnt/β-catenin pathway

2020 ◽  
Author(s):  
Weiyuan Li ◽  
Ganggang Yang ◽  
Dengke Yang ◽  
Dong Li ◽  
Qian Sun
Keyword(s):  
Cell Proliferation ◽  
Migration And Invasion ◽  
Biological Processes ◽  
Sequencing Technology ◽  
Next Generation Sequencing Technology ◽  
Normal Tissues ◽  
Factor C ◽  
Generation Sequencing

Abstract Background Long noncoding RNAs (lncRNAs), which are important functional regulators in cancer, have emerged as critical molecular regulators in various biological processes. However, the mechanisms by which LEF1-AS1 modulates Androgen-Independent Prostate Cancer (AIPC) development remain largely unknown. Methods The LEF1-AS1 expression level was detected in tumour tissues and adjacent normal tissues of AIPC patients by using next-generation sequencing technology and qRT-PCR. Cell proliferation, migration and invasion were assessed by colony formation, EDU assays and transwell assays, respectively. Xenograft assay was conducted to determine the effect of LEF1-AS1 on cell proliferation in vivo. Results LEF1-AS1 promoted the proliferation, migration, invasion and angiogenic ability of AIPC cells in vitro and in vivo. In this mechanism, LEF1-AS1 recruited the transcription factor C-myb to the promoter region of FZD2, which activated FZD2 transcription. Moreover, LEF1-AS1 functioned as a competing endogenous RNA (ceRNA) acting as a sponge for miR-328, which activated CD44. Conclusion Collectively, these data indicate that LEF1-AS1 is a tumour promoter in the development of AIPC and that it may contribute to the improvement of AIPC diagnosis and therapy.

scholarly journals Degradation of long non-coding RNA-CIR decelerates proliferation, invasion and migration, but promotes apoptosis of osteosarcoma cells

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Shiwei Liu ◽  
Jingchao Li ◽  
Liang Kang ◽  
Yueyang Tian ◽  
Yuan Xue
Keyword(s):  
Tumor Growth ◽  
Osteosarcoma Cell ◽  
Loss Of Function ◽  
Osteosarcoma Cells ◽  
Invasion And Migration ◽  
Normal Tissues ◽  
Novel Target ◽  
And Migration

Abstract Background Over the years, long non-coding RNAs (lncRNAs) have been clarified in malignancies, this research was focused on the role of lncRNA cartilage injury-related (lncRNA-CIR) in osteosarcoma cells. Methods LncRNA-CIR expression in osteosarcoma tissues and cells, and adjacent normal tissues and normal osteoblasts was determined, then the relations between lncRNA-CIR expression and the clinicopathological features, and between lncRNA-CIR expression and the prognosis of osteosarcoma patients were analyzed. Moreover, the MG63 and 143B cells were treated with silenced or overexpressed lncRNA-CIR, and then the proliferation, invasion, migration and apoptosis of the cells were evaluated by gain- and loss-of-function approaches. The tumor growth, and proliferation and apoptosis of osteosarcoma cells in vivo were observed by subcutaneous tumorigenesis in nude mice. Results We have found that lncRNA-CIR was up-regulated in osteosarcoma tissues and cells, which was respectively relative to adjacent normal tissues and normal osteoblasts. The expression of lncRNA-CIR was evidently correlated with disease stages, distant metastasis and differentiation of osteosarcoma patients, and the high expression of lncRNA-CIR indicated a poor prognosis. Furthermore, the reduction of lncRNA-CIR could restrict proliferation, invasion and migration, but promote apoptosis of osteosarcoma cells in vitro. Meanwhile, inhibited lncRNA-CIR also restrained tumor growth and osteosarcoma cell proliferation, whereas accelerated apoptosis of osteosarcoma cells in vivo. Conclusion We have found in this study that the inhibited lncRNA-CIR could decelerate proliferation, invasion and migration, but accelerate apoptosis of osteosarcoma cells, which may provide a novel target for osteosarcoma treatment.

scholarly journals miR-206 Inhibits Cell Proliferation, Migration, and Invasion by Targeting BAG3 in Human Cervical Cancer

2018 ◽  
Vol 26 (6) ◽  
pp. 923-931 ◽  
Author(s):  
Yingying Wang ◽  
Yongjie Tian
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Protein Expression ◽  
Xenograft Model ◽  
Migration And Invasion ◽  
Normal Tissues ◽  
Bax Protein ◽  
Cancer Types

miR-206 and Bcl-2-associated athanogene 3 (BAG3) have been suggested as important regulators in various cancer types. However, the biological role of miR-206 and BAG3 in cervical cancer (CC) remains unclear. We investigated the expressions and mechanisms of miR-206 and BAG3 in CC using in vitro and in vivo assays. In the present study, miR-206 expression was expressed at a lower level in CC tissues and cells than adjacent normal tissues and NEECs. By contrast, BAG3 mRNA and protein were expressed at higher levels in CC tissues and cells. Furthermore, miR-206 overexpression repressed cell proliferation, migration, and invasion in vitro, and the 3′-untranslated region (3′-UTR) of BAG3 was a direct target of miR-206. miR-206 overexpression also inhibited EGFR, Bcl-2, and MMP2/9 protein expression, but promoted Bax protein expression. Besides, BAG3 overexpression partially abrogated miR-206-inhibited cell proliferation and invasion, while BAG3 silencing enhanced miR-206-mediated inhibition. In vivo assay revealed that miR-206 repressed tumor growth in nude mice xenograft model. In conclusion, miR-206 inhibits cell proliferation, migration, and invasion by targeting BAG3 in human CC. Thus, miR-206-BAG3 can be used as a useful target for CC.

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