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 Panax Notoginseng Saponins Exert Anti-osteosarcoma Effect by Inhibiting G0 / G1 Phase and Affecting p53-mediated Autophagy and Mitochondrial Apoptosis

2021 ◽  
Author(s):  
Guangtao Han ◽  
Ting Liu
Keyword(s):  
Cell Cycle ◽  
Panax Notoginseng ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Panax Notoginseng Saponins ◽  
Active Components ◽  
Invasion And Migration ◽  
And Migration

Abstract BackgroundOsteosarcoma is the most common primary bone malignancy. Chemotherapy for osteosarcoma often induces severe complications to the patients. Thus, the identification of new effective antineoplastic agents with fewer side effects remain a necessity. Panax notoginseng saponins (PNS) were therapeutic active components of panax notoginseng and were reported taking the capability to inhibit the growth of several tumors in vitro and in vivo. However, its effect on osteosarcoma has not been studied. This study first investigated the effect of PNS on osteosarcoma cells.MethodsCCK-8 essay used to determine the appropriate working concentration of PNS on osteosarcoma,annixV-FITC/PI experiment used to measure the apoptosis of PNS on osteosarcoma, wound healing assay was used to detect the migration of PNS on osteosarcoma, cell invasiveness was measured by transwell essay,cell cycle was measured by PI,the expression of relative protein was shown by western blot.ResultsOur result indicated that PNS inhibited osteosarcoma cells’ proliferation, invasion and migration, promoted their apoptosis. Besides, PNS also increased mitochondrial membrane potential and the level of reactive oxygen species. Cell cycle of osteosarcoma was arrested in G0 / G1 phase after treatment with PNS. The expression of p53, and mitochondrial related apoptosis proteins were promoted; however, decreased autophagy in osteosarcoma cells with PNS treatment were observed.ConclusionTaking the above effect of PNS on osteosarcoma, PNS were of the potential therapeutic value for treatment of osteosarcoma.

scholarly journals miR-23a-3p is a Key Regulator of IL-17C-Induced Tumor Angiogenesis in Colorectal Cancer

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1363 ◽  
Author(s):  
Yunna Lee ◽  
Su Jin Kim ◽  
Jieun Choo ◽  
Gwangbeom Heo ◽  
Jin-Wook Yoo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Tumor Angiogenesis ◽  
Ex Vivo ◽  
Underlying Mechanism ◽  
Vegf Receptor ◽  
Invasion And Migration ◽  
Novel Target ◽  
And Migration

MicroRNAs (miRNAs) have emerged as key players in tumor angiogenesis. Interleukin-17C (IL-17C) was identified to promote colorectal cancer (CRC) progression. Therefore, we aimed to investigate the effect of IL-17C on tumor angiogenesis, the involvement of miR-23a-3p in IL-17C signaling, and the direct target gene of miR-23a-3p in CRC. In vitro and ex vivo angiogenesis, a mouse xenograft experiment, and immunostaining were performed to test the effect of IL-17C on tumor angiogenesis. ELISA, quantitative real time PCR, and gene silencing were used to uncover the underlying mechanism. IL-17C induced angiogenesis of intestinal endothelial cells, subsequently enhancing cell invasion and migration of DLD-1 cells. IL-17C-stimulated DLD-1 cells produced vascular endothelial growth factor (VEGF) to enhance angiogenesis. Moreover, IL-17C markedly accelerated xenograft tumor growth, which was manifested by substantially reduced tumor growth when treated with the VEGF receptor 2 inhibitor Ki8751. Accordingly, Ki8751 suppressed the expression of IL-17C-stimulated PECAM and VE-cadherin in xenografts. Furthermore, IL-17C activated STAT3 to increase the expression of miR-23a-3p that suppressed semaphorin 6D (SEMA6D) expression, thereby permitting VEGF production. Taken together, our study demonstrates that IL-17C promotes tumor angiogenesis through VEGF production via a STAT3/miR-23a-3p/SEMA6D axis, suggesting its potential as a novel target for anti-CRC therapy.

scholarly journals Homeodomain-containing gene 10 inhibits cell apoptosis and promotes cell invasion and migration in osteosarcoma cell lines

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831769756 ◽  
Author(s):  
Wen Xiong ◽  
Quan Zhou ◽  
Gang Liu ◽  
Xiang-Sheng Liu ◽  
Xin-Yu Li
Keyword(s):  
Cell Apoptosis ◽  
Bone Cyst ◽  
Molecular Target ◽  
The Cancer Genome Atlas ◽  
Osteosarcoma Cell ◽  
Invasion And Migration ◽  
Mg63 Cells ◽  
And Migration

Homeodomain-containing gene 10 (HOXC10) belongs to the homeobox family, which encodes a highly conserved family of transcription factors that plays an important role in morphogenesis in all multicellular organisms. Altered expressions of HOXC10 have been reported in several malignancies. This study was aimed to reveal the expression profile of HOXC10 in osteosarcoma and evaluated whether HOXC10 is a molecular target for cancer therapy. We found that HOXC10 was up-regulated in osteosarcoma tissues compared with bone cyst specimens from The Cancer Genome Atlas database. Osteosarcoma MG63 cells were infected with HOXC10 shRNA expressing vector, and 143B cells were infected with HOXC10 expressing vector. We found that reduced expression of HOXC10 markedly impaired the ability of proliferation, invasion, and migration, and promoted cell apoptosis in vitro and in vivo. Up-regulated expression of HOXC10 promoted the proliferation, invasion, and migration, and inhibited apoptosis of 143B cells. Additionally, HOXC10 regulated apoptosis and migration via modulating expression of Bax/Bcl-2, caspase-3, MMP-2/MMP-9, and E-cadherin in both MG63 and 143B cells and in vivo. These results indicated that HOXC10 might be a diagnostic marker for osteosarcoma and could be a potential molecular target for the therapy of osteosarcoma.

scholarly journals HDAC3 deteriorates colorectal cancer progression via microRNA-296-3p/TGIF1/TGFβ axis

2020 ◽  
Vol 39 (1) ◽  
Author(s):  
Jinxiao Li ◽  
Man Hu ◽  
Na Liu ◽  
Huarong Li ◽  
Zhaomin Yu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Growth ◽  
Luciferase Reporter ◽  
Invasion And Migration ◽  
Induction Of Apoptosis ◽  
And Migration ◽  
Related Proteins ◽  
Tgfβ Pathway

Abstract Background The mechanism of histone deacetylase 3 (HDAC3) in colorectal cancer (CRC) has already been discussed. However, the feedback loop of HDAC3/microRNA (miR)-296-3p and transforming growth factor β-induced factor 1 (TGIF1) in CRC has not been explained clearly. Thus, the mainstay of this study is to delve out the mechanism of this axis in CRC. Methods To demonstrate that HDAC3 regulates the miR-296-3p/TGIF1/TGFβ axis and is involved in CRC progression, a series of cell biological, molecular and biochemical approaches were conducted from the clinical research level, in vitro experiments and in vivo experiments. These methods included RT-qPCR, Western blot assay, cell transfection, MTT assay, EdU assay, flow cytometry, scratch test, Transwell assay, dual luciferase reporter gene assay, chromatin immunoprecipitation, nude mouse xenograft, H&E staining and TUNEL staining. Results Higher HDAC3 and TGIF1 and lower miR-296-3p expression levels were found in CRC tissues. HDAC3 was negatively connected with miR-296-3p while positively correlated with TGIF1, and miR-296-3p was negatively connected with TGIF1. Depleted HDAC3 elevated miR-296-3p expression and reduced TGIF1 expression, decreased TGFβ pathway-related proteins, inhibited CRC proliferation, invasion, and migration in vitro and slowed down tumor growth and induction of apoptosis in vivo, which were reversed by miR-296-3p knockdown. Restored miR-296-3p suppressed TGIF1 and reduced TGFβ pathway-related proteins, inhibited CRC proliferation, invasion, and migration in vitro and slowed down tumor growth and induction of apoptosis in vivo, which were reversed by TGIF1 overexpression. Conclusion This study illustrates that down-regulation of HDAC3 or TGIF1 or up-regulation of miR-296-3p discourages CRC cell progression and slows down tumor growth, which guides towards a novel direction of CRC treatment.

Knockdown of Kinesin Family 15 Inhibits Osteosarcoma through Suppressing Cell Proliferation and Promoting Cell Apoptosis

Chemotherapy ◽  
2019 ◽  
Vol 64 (4) ◽  
pp. 187-196
Author(s):  
Zhiqiang Wu ◽  
Hao Zhang ◽  
Zhengwang Sun ◽  
Chunmeng Wang ◽  
Yong Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Flow Cytometric Analysis ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Expression Levels ◽  
Invasion And Migration ◽  
Normal Tissues ◽  
And Migration ◽  
Kinesin Family

Kinesin family (KIF) members have vital roles in mitosis, meiosis, and transport of macromolecules in eukaryotic cells. In this study, we aimed to investigate the role of KIF15 in osteosarcoma. Immunohistochemical staining was performed to determine expression levels of KIF15 in osteosarcoma tissues and adjacent normal tissues. Tissue microarray analysis showed a correlation between the expression of KIF15 and pathological features of patients. Subsequently, lentivirus was used to inhibit the expression of KIF15 in osteosarcoma cells. An MTT assay was performed to examine cell proliferation. Transwell and wound healing assays were used to estimate the invasion and migration of osteosarcoma cells, respectively. Flow cytometric analysis was employed to define the apoptosis of osteosarcoma cells. Our results showed that KIF15 expression was significantly upregulated in osteosarcoma tissues compared with adjacent normal tissues. The Mann-Whitney U test and Spearman correlation analysis showed that the expression levels of KIF15 in osteosarcoma tissues were positively correlated with tumor infiltrate, a pathological characteristic of patients. The expression of KIF15 was successfully suppressed by shKIF15, and the knockdown efficiency reached 80 and 69% in MNNG/HOS and U2OS cells, respectively. Subsequently, knockdown of KIF15 significantly inhibited the capacity of cell proliferation, colony formation, invasion, and migration, but enhanced G2 phase arrest and partially enhanced cell apoptosis. This study preliminarily showed KIF15 to be a critical regulatory molecule involved in osteosarcoma cell proliferation. Consequently, KIF15 can be a potential diagnostic and therapeutic target for osteosarcoma.

scholarly journals α-Solanine Inhibits Proliferation, Invasion, and Migration, and Induces Apoptosis in Human Choriocarcinoma JEG-3 Cells In Vitro and In Vivo

Toxins ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 210
Author(s):  
Ting Gu ◽  
Wei Yuan ◽  
Chen Li ◽  
Zhilong Chen ◽  
Yuting Wen ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Bioactive Compound ◽  
Nuclear Antigen ◽  
Migration And Invasion ◽  
Multiple Cancer ◽  
Invasion And Migration ◽  
Choriocarcinoma Cells ◽  
And Migration

α-Solanine, a bioactive compound mainly found in potato, exhibits anti-cancer activity towards multiple cancer cells. However, its effects on human choriocarcinoma have not been evaluated. In the present study, we investigated the effect of α-solanine on cell proliferation and apoptosis in human choriocarcinoma in vitro and in vivo. The results showed that α-solanine, at concentrations of 30 μM or below, did not affect the cell viability of the choriocarcinoma cell line JEG-3. However, colony formation was significantly decreased and cell apoptosis was increased in response to 30 μM α-solanine. In addition, α-solanine (30 μM) reduced the migration and invasion abilities of JEG-3 cells, which was associated with a downregulation of matrix metalloproteinases (MMP)-2/9. The in vivo findings provided further evidence of the inhibition of α-solanine on choriocarcinoma tumor growth. α-Solanine suppressed the xenograft tumor growth of JEG-3 cells, resulting in smaller tumor volumes and lower tumor weights. Apoptosis was promoted in xenograft tumors of α-solanine-treated mice. Moreover, α-solanine downregulated proliferative cellular nuclear antigen (PCNA) and Bcl-2 levels and promoted the expression of Bax. Collectively, α-solanine inhibits the growth, migration, and invasion of human JEG-3 choriocarcinoma cells, which may be associated with the induction of apoptosis.

scholarly journals piR-hsa-211106 Inhibits the Progression of Lung Adenocarcinoma Through Pyruvate Carboxylase and Enhances Chemotherapy Sensitivity

2021 ◽  
Vol 11 ◽  
Author(s):  
Yongmei Liu ◽  
Yanhan Dong ◽  
Xinjia He ◽  
Anjing Gong ◽  
Jinning Gao ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Therapeutic Target ◽  
Pyruvate Carboxylase ◽  
Loss Of Function ◽  
Chemotherapy Sensitivity ◽  
Normal Tissues ◽  
Mechanistic Investigation ◽  
And Migration

Although the importance of PIWI-interacting RNAs (piRNAs) in cancer has recently been recognized, studies on the role and functional mechanism of piRNAs in lung adenocarcinoma (LUAD) development and progression are limited. In this study, we identified 10 differently expressed piRNAs in LUAD tissues compared to normal tissues, among which, piR-hsa-211106 expression levels were downregulated in LUAD tissues and cell lines. Furthermore, the effects of piR-hsa-211106 on the malignant phenotypes and chemosensitivity of LUAD cells were detected by gain- and loss-of-function analyses in vitro and in vivo, which showed that piR-hsa-211106 inhibited LUAD cell proliferation, tumor growth, and migration, but promoted apoptosis. Moreover, our finding indicated that piR-hsa-211106 is a potential therapeutic target that synergistically imparts anticancer effects with a chemotherapeutic agent for LUAD-cisplatin. Further mechanistic investigation indicated that piR-hsa-211106 could bind to pyruvate carboxylase (PC) by RNA pull down and RNA immunoprecipitation assays and inhibited PC mRNA and protein expression. Our study demonstrates that piR-hsa-211106 inhibits LUAD progression by hindering the expression and function of PC and enhances chemotherapy sensitivity, suggesting that piR-hsa-211106 is a novel diagnostic and therapeutic target for LUAD.

Amentoflavone Effectively Blocked the Tumor Progression of Glioblastoma via Suppression of ERK/NF-κB Signaling Pathway

2019 ◽  
Vol 47 (04) ◽  
pp. 913-931 ◽  
Author(s):  
Fei-Ting Hsu ◽  
I-Tsang Chiang ◽  
Yu-Cheng Kuo ◽  
Te-Chun Hsia ◽  
Chin-Chung Lin ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Signaling Pathway ◽  
Unmet Need ◽  
In Vivo Studies ◽  
Tumor Growth Inhibition ◽  
Beneficial Result ◽  
Invasion And Migration ◽  
And Migration

Glioblastoma is the most common primary malignant tumor of the central nervous system, with an annual incidence of 5.26 per 100000 people. The clinical outcome of standard therapy and the survival rate remain poor; therefore, there is an unmet need for a new strategy to treat this lethal disease. Although amentoflavone was known to have anticancer potential in various types of cancers, its antiglioblastoma ability and mechanism remain unrecognized. We demonstrated that amentoflavone may suppress glioblastoma invasion and migration by transwell assay. Moreover, we established NF-[Formula: see text]B reporter gene system and used that for verifying NF-[Formula: see text]B inhibition efficacy of amentoflavone on in vitro and in vivo studies. Here, we indicated that amentoflavone not only diminished NF-[Formula: see text]B activation, but also reduced NF-[Formula: see text]B-mediated downstream oncogenes expression, such as MMP-2, MMP-9, XIAP, cyclinD1 and VEGF, which was elucidated by Western blot and immunohistochemistry (IHC). Tumor growth inhibition and NF-[Formula: see text]B reduction was found in the amentoflavone treatment group, which was revealed by the glioblastoma-bearing animal model. In this study, we also used ERK inhibitor and NF-[Formula: see text]B inhibitor (QNZ) to confirm whether the beneficial result of amentoflavone on glioblastoma was mainly regulated by blockage of ERK/NF-[Formula: see text]B signaling. In summary, ERK/NF-[Formula: see text]B signaling pathway has a role in the inhibition of tumor growth by amentoflavone in glioblastoma.

scholarly journals Exosomal miR-1228 From Cancer-Associated Fibroblasts Promotes Cell Migration and Invasion of Osteosarcoma by Directly Targeting SCAI

2019 ◽  
Vol 27 (9) ◽  
pp. 979-986 ◽  
Author(s):  
Jian-Wei Wang ◽  
Xiao-Feng Wu ◽  
Xiao-Juan Gu ◽  
Xing-Hua Jiang
Keyword(s):  
Cell Migration ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Cancer Associated Fibroblasts ◽  
Osteosarcoma Cells ◽  
Mirna Microarray ◽  
Cell Migration And Invasion ◽  
Invasion And Migration ◽  
And Migration

Cancer-associated fibroblasts (CAFs) play a predominant role in regulating tumor progression. Understanding how CAFs communicate with osteosarcoma is crucial for developing novel approaches for osteosarcoma therapy. Exosomes are able to transmit messages between cells. In this study, we demonstrated that CAFs transfer exosomes to osteosarcoma cells, which promotes osteosarcoma cell migration and invasion. Using a miRNA microarray analysis, we identified 13 miRNAs that are significantly increased in exosomes derived from cancer-associated fibroblasts (CAFs) and corresponding paracancer fibroblasts (PAFs). In vitro studies further validated that the levels of microRNA-1228 (miR-1228) were increased in CAFs, its secreted exosomes, and in recipient osteosarcoma cells, which can downregulate endogenous SCAI mRNA and protein level in osteosarcoma. Furthermore, our findings demonstrate that SCAI was downregulated in osteosarcoma tissues. Taken together, this study provides evidence that CAF exosomal miR-1228 is able to promote osteosarcoma invasion and migration by targeting SCAI, which may represent a critical therapeutic target for osteosarcoma treatment.

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