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

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.

Download Full-text

Down-regulation of microRNA-34a-5p promotes trophoblast cell migration and invasion via targetting Smad4

Bioscience Reports ◽

10.1042/bsr20181631 ◽

2019 ◽

Vol 39 (2) ◽

Cited By ~ 7

Author(s):

Fang Xue ◽

Jing Yang ◽

Qirong Li ◽

Haibin Zhou

Keyword(s):

Cell Migration ◽

Expression Profiles ◽

Trophoblast Cell ◽

Migration And Invasion ◽

Cell Migration And Invasion ◽

Invasion And Migration ◽

Luciferase Activity Assay ◽

Cell Invasiveness ◽

And Migration ◽

Mirnas Expression

Abstract Trophoblastic dysfunction, such as insufficient migration and invasion, is well-known to be correlated with preeclampsia (PE). Recently, microRNAs (miRNAs) have been implicated in diverse biological processes and human diseases, including PE. However, the expression and functions of miRNAs in the progression of PE, especially in the regulation of trophoblast cell migration and invasion remain largely unclear. Here, we compared the miRNAs expression profiles of PE patients with healthy controls using microarray assay and chose a significant increased miRNA-miR-34a-5p for further investigation. Overexpression of miR-34a-5p dramatically reduced migration and invasion in trophoblast HTR-8/SVneo cells, whereas enhanced by its inhibitor. Luciferase activity assay showed that miR-34a-5p directly target Smad family member 4 (Smad4), which is associated with cancer cell invasiveness and metastasis. We also found that Smad4 was down-regulated in PE patients, and an inverse relationship between Smad4 and miR-34a-5p expression levels was observed in placental tissues from PE patients. Further study showed that knockdown of Smad4 effectively attenuated the promoting effects of miR-34a-5p inhibition on the migration and invasion of HTR-8/SVneo cells. Taken together, these findings suggest that inhibition of miR-34a-5p improves invasion and migration of trophoblast cells by directly targetting Smad4, which indicated the potential of miR-34a-5p as a therapeutic target against PE.

Download Full-text

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

Cancer Cell International ◽

10.1186/s12935-019-1076-7 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 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.

Download Full-text

GAPLINC is a predictor of poor prognosis and regulates cell migration and invasion in osteosarcoma

Bioscience Reports ◽

10.1042/bsr20181171 ◽

2018 ◽

Vol 38 (5) ◽

Cited By ~ 1

Author(s):

Shian Liao ◽

Sijia Zhou ◽

Chao Wang

Keyword(s):

Cell Migration ◽

Cell Lines ◽

Histological Grade ◽

Migration And Invasion ◽

Clinical Samples ◽

Osteosarcoma Cell ◽

Loss Of Function ◽

Cell Migration And Invasion ◽

Potential Biomarker

Gastric adenocarcinoma predictive long intergenic non-coding (GAPLINC) is a novel long non-coding RNA (lncRNA) and has been found to function as an oncogenic lncRNA in gastric cancer, colorectal cancer, and bladder cancer. The expression status and biological function of GAPLINC in osteosarcoma are still unknown. Thus, we analyzed the association between GAPLINC expression and clinicopathological characteristics in osteosarcoma clinical samples, and conducted loss-of-function study in osteosarcoma cell lines. In our results, GAPLINC expression is elevated in osteosarcoma tissues and cell lines, and correlated with advanced Enneking stage, present distant metastasis, and poor histological grade. Survival analyses indicated that GAPLINC expression was negatively associated with overall survival, and GAPLINC high-expression was an independent risk factor in osteosarcoma patients. The in vitro studies showed knockdown of GAPLINC depressed osteosarcoma cell migration and invasion via inhibiting CD44 expression, but no effect on cell proliferation. In conclusion, GAPLINC may serve as a potential biomarker for predicting prognosis and developing therapy for osteosarcoma.

Download Full-text

Inhibiting roles of FOXA2 in hepatocellular carcinoma cell migration and invasion by transcriptionally suppressing microRNA-103a-3p and activating the GREM2/LATS2 axis

10.21203/rs.3.rs-26285/v1 ◽

2020 ◽

Author(s):

Guangzhen Ma ◽

Jirong Chen ◽

Tiantian Wei ◽

Jia Wang ◽

Wenshan Chen

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Migration ◽

Luciferase Assay ◽

Migration And Invasion ◽

Altered Expression ◽

Cell Migration And Invasion ◽

Invasion And Migration ◽

Forkhead Box ◽

And Migration

Abstract Background Forkhead box A2 (FOXA2) is a transcriptional activator for liver-specific genes. Hepatocellular carcinoma (HCC) is a prevalent fetal malignancy across the globe. This work focused on the role of FOXA2 in HCC cell migration and invasion and the involving molecules. Methods FOXA2 expression in HCC tissues and cells was determined using RT-qPCR. Altered expression of FOXA2 was introduced to identify its role in HCC cell migration and invasion using Transwell assays. The potential target microRNA (miRNA) of FOXA2 was predicted via online prediction and validated through a ChIP assay, and the mRNA target of miRNA-103a-3p was predicted and confirmed through a luciferase assay. The roles of miR-103a-3p and GREM2 in HCC cell invasion and migration were determined, and the downstream molecules mediated by GREM2 were analyzed. Results FOXA2 and GREM2 were poorly expressed while miR-103a-3p was abundant in HCC tissues and cells. Overexpression of FOXA2 or GREM2 suppressed migration and invasion of HepG2 and SK-HEP-1 cells, while up-regulation of miR-103a-3p led to reverse trends. FOXA2 transcriptionally suppressed miR-103a-3p to increase GREM2 expression, and silencing of GREM2 partially blocked the inhibitory effects of FOXA2 on cell migration and invasion. GREM2 increased LATS2 activity and YAP phosphorylation and degradation. Conclusion This study evidenced that FOXA2 inhibits migration and invasion potentials of HCC cell lines through suppressing miR-103a-3p transcription. The following upregulation of GREM2 plays key roles in migration inhibition by promoting LATS2 activity and YAP phosphorylation. This study may offer new insights into HCC treatment.

Download Full-text

lncRNA DLGAP1-AS2 Knockdown Inhibits Hepatocellular Carcinoma Cell Migration and Invasion by Regulating miR-154-5p Methylation

BioMed Research International ◽

10.1155/2020/6575724 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Kai Chen ◽

Zhuqing Zhang ◽

Aijun Yu ◽

Jian Li ◽

Jinlong Liu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Migration ◽

Migration And Invasion ◽

Altered Expression ◽

Cell Migration And Invasion ◽

Invasion And Migration ◽

Specific Pcr ◽

And Migration ◽

Hcc Cells

Objective. DLGAP1-AS2 has been characterized as an oncogenic lncRNA in glioma. Our preliminary microarray analysis revealed the altered expression of DLGAP1-AS2 in hepatocellular carcinoma (HCC), but the role of DLGAP1-AS2 in HCC remains unknown. Method. Expression of DLGAP1-AS2 and miR-154-5p in paired HCC and nontumor tissues from 62 HCC patients was determined by RT-qPCR. The 62 HCC patients were followed up for 5 years to analyze the prognostic value of DLGAP1-AS2 for HCC. DLGAP1-AS2 knockdown and miR-154-5p overexpression was achieved in HCC cells to study the relationship between them. Methylation of miR-154-5p was analyzed by methylation-specific PCR. Cell proliferation was analyzed by CCK-8 assay. Results. DLGAP1-AS2 was upregulated in HCC and predicted poor survival. miR-154-5p was downregulated in HCC and inversely correlated with DLGAP1-AS2. In HCC cells, DLGAP1-AS2 knockdown resulted in the upregulation of miR-154-5p expression and decreased methylation of miR-154-5p gene. Transwell assay showed that DLGAP1-AS2 knockdown and miR-154-5p overexpression inhibited cell invasion and migration, and the combination of LGAP1-AS2 knockdown and miR-154-5p overexpression showed stronger effects. Conclusion. DLGAP1-AS2 knockdown may inhibit HCC cell migration and invasion by regulating miR-154-5p methylation.

Download Full-text

LncRNA DLGAP1-AS2 SiRNA Silencing Inhibits Hepatocellular Carcinoma Cell Migration and Invasion by Up-regulating MiR-154-5p Through Methylation

10.21203/rs.3.rs-37419/v1 ◽

2020 ◽

Author(s):

Kai Chen ◽

Zhuqing Zhang ◽

Aijun Yu ◽

Jian Li ◽

Jinlong Liu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cell Migration ◽

Migration And Invasion ◽

Cell Migration And Invasion ◽

Invasion And Migration ◽

Specific Pcr ◽

Tumor Tissues ◽

Sirna Silencing ◽

And Migration ◽

Hcc Cells

Abstract Background:DLGAP1-AS2 has been characterized as an oncogenic lncRNA in glioma. This study was performed to explore the role of DLGAP1-AS2 in hepatocellular carcinoma (HCC). Methods:Expression of DLGAP1-AS2 and miR-154-5p in paired HCC and non-tumor tissues from 62 HCC patients was determined by RT-qPCR. The 62 HCC patients were followed up for 5 years to analyze the prognostic value of DLGAP1-AS2 for HCC. DLGAP1-AS2 siRNA silencing and miR-154-5p overexpression was achieved in HCC cells to study the relationship between them. Methylation of miR-154-5p was analyzed by methylation-specific PCR. Cell proliferation was analyzed by CCK-8 assay.Results: DLGAP1-AS2 was upregulated in HCC and predicted poor survival. MiR-154-5p was downregulated in HCC and inversely correlated with DLGAP1-AS2. In HCC cells, DLGAP1-AS2 siRNA silencing resulted in the upregulation of miR-154-5p and decreased methylation of miR-154-5p gene. Transwell assay showed that, DLGAP1-AS2 siRNA silencing and miR-154-5p overexpression inhibited cell invasion and migration, and the combination of LGAP1-AS2 siRNA silencing and miR-154-5p overexpression showed stronger effects.Conclusion: DLGAP1-AS2 siRNA silencing may inhibit HCC cell migration and invasion by up-regulating miR-154-5p through methylation.

Download Full-text

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

10.21203/rs.3.rs-138936/v1 ◽

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.

Download Full-text

Study of LBHD1 Expression with Invasion and Migration of Bladder Cancer

Open Life Sciences ◽

10.1515/biol-2019-0049 ◽

2019 ◽

Vol 14 (1) ◽

pp. 440-447

Author(s):

Chunhui Dong ◽

Yihui Liu ◽

Guiping Yu ◽

Xu Li ◽

Ling Chen

Keyword(s):

Cell Proliferation ◽

Bladder Cancer ◽

Cell Migration ◽

Cancer Cells ◽

Tumor Antigens ◽

Urinary Bladder Cancer ◽

Migration And Invasion ◽

Cell Migration And Invasion ◽

Invasion And Migration ◽

Bladder Cancer Cells

AbstractLBHD1 (C11ORF48) is one of the ten potential tumor antigens identified by immunoscreening the urinary bladder cancer cDNA library in our previous study. We suspect that its expression is associated with human bladder cancer. However, the exact correlation remains unclear. To address the potential functional relationship between LBHD1 and bladder cancer, we examined the LBHD1 expression at the mRNA and protein level in 5 different bladder cancer cell lines: J82, T24, 253J, 5637, and BLZ-211. LBHD1 high and low expressing cells were used to investigate the migration, invasion, and proliferation of bladder cancer cells following transfection of LBHD1 with siRNA and plasmids, respectively. Our experiment showed that the degree of gene expression was positively related to the migration and invasion of the cancer cells while it had little effect on cell proliferation. Knocking down LBHD1 expression with LBHD1 siRNA significantly attenuated cell migration and invasion in cultured bladder cancer cells, and overexpressing LBHD1 with LBHD1 cDNA plasmids exacerbated cell migration and invasion. Nevertheless, a difference in cell proliferation after transfection of LBHD1 siRNA and LBHD1 cDNA plasmids was not found. Our findings suggest that LBHD1 might play a role in cell migration and invasion.

Download Full-text

Resveratrol Enhances Inhibition Effects of Cisplatin on Cell Migration and Invasion and Tumor Growth in Breast Cancer MDA-MB-231 Cell Models In Vivo and In Vitro

Molecules ◽

10.3390/molecules26082204 ◽

2021 ◽

Vol 26 (8) ◽

pp. 2204

Author(s):

Meng-Die Yang ◽

Yang Sun ◽

Wen-Jun Zhou ◽

Xiao-Zheng Xie ◽

Qian-Mei Zhou ◽

...

Keyword(s):

Breast Cancer ◽

Cell Migration ◽

Tumor Growth ◽

Cell Viability ◽

Synergistic Effects ◽

Migration And Invasion ◽

Cell Migration And Invasion ◽

Tgf Β1

Triple-negative breast cancer (TNBC) is a refractory type of breast cancer that does not yet have clinically effective drugs. The aim of this study is to investigate the synergistic effects and mechanisms of resveratrol combined with cisplatin on human breast cancer MDA-MB-231 (MDA231) cell viability, migration, and invasion in vivo and in vitro. In vitro, MTS assays showed that resveratrol combined with cisplatin inhibits cell viability as a concentration-dependent manner, and produced synergistic effects (CI < 1). Transwell assay showed that the combined treatment inhibits TGF-β1-induced cell migration and invasion. Immunofluorescence assays confirmed that resveratrol upregulated E-cadherin expression and downregulated vimentin expression. Western blot assay demonstrated that resveratrol combined with cisplatin significantly reduced the expression of fibronectin, vimentin, P-AKT, P-PI3K, P-JNK, P-ERK, Sma2, and Smad3 induced by TGF-β1 (p < 0.05), and increased the expression of E-cadherin (p < 0.05), respectively. In vivo, resveratrol enhanced tumor growth inhibition and reduced body weight loss and kidney function impairment by cisplatin in MDA231 xenografts, and significantly reduced the expressions of P-AKT, P-PI3K, Smad2, Smad3, P-JNK, P-ERK, and NF-κB in tumor tissues (p < 0.05). These results indicated that resveratrol combined with cisplatin inhibits the viability of breast cancer MDA231 cells synergistically, and inhibits MDA231 cells invasion and migration through Epithelial-mesenchymal transition (EMT) approach, and resveratrol enhanced anti-tumor effect and reduced side of cisplatin in MDA231 xenografts. The mechanism may be involved in the regulations of PI3K/AKT, JNK, ERK and NF-κB expressions.

Download Full-text