scholarly journals Downregulation of Rap1GAP Expression Activates the TGF-β/Smad3 Pathway to Inhibit the Expression of Sodium/Iodine Transporter in Papillary Thyroid Carcinoma Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Zheng Yan ◽  
Wang Yangyanqiu ◽  
Han Shuwen ◽  
Mao Jing ◽  
Liao Haihong ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Suppressor Gene ◽  
Immunofluorescence Assay ◽  
Migration And Invasion ◽  
Papillary Thyroid ◽  
Protein Levels ◽  
Cell Functions ◽  
Cell Proliferative Activity ◽  
Related Proteins ◽  
Tgf Β1

Objective. Rap1GAP is considered a tumor suppressor gene, but its regulatory mechanism in papillary thyroid cancer (PTC) has not been clearly elucidated. The aim of this study was to explore whether the regulation between Rap1GAP and sodium/iodine transporter (NIS) in tumorigenesis of PTC is mediated by TGF-β1. Methods. Western blotting (WB) and quantitative reverse-transcription polymerase chain reaction were performed to analyze the relationships between TGF-β1 concentration and NIS expression. After transfecting BCPAP cells with siRNAs, the Rap1GAP interference model was successfully established. Then, the expression and nuclear localization of TGF-β1 and pathway-related proteins were detected. Flow cytometry was applied to analyze cell apoptosis and cycle. WB was performed to detect apoptotic-related proteins. Wound healing and transwell assays were used to measure cell migration and invasion. EDU was performed to detect cell proliferative activity. Results. The results suggested that TGF-β1 could significantly inhibit the expression of NIS in both mRNA and protein levels. In BCPAP cells transfected with siRNA-Rap1GAP, the expression levels of TGF-β1, Foxp3, and p-Smad3 were significantly increased. By applying immunofluorescence assay, the nuclear localizations of TβR-1 and p-Smad3 were found to be activated. Moreover, anti-TGF-β1 can reverse the decrease in NIS expression caused by downregulation of Rap1GAP. Additionally, the knockdown of Rap1GAP could alter the cell apoptosis, cycle, migration, invasion, and proliferation of BCPAP. Conclusion. The downregulation of Rap1GAP expression can activate the TGF-β/Smad3 pathway to inhibit NIS expression and alter the tumor cell functions of PTC.

FOXD3 inhibits cell proliferation, migration, and invasion in nasopharyngeal carcinoma through regulation of the PI3K–Akt pathway

2020 ◽  
Vol 98 (6) ◽  
pp. 653-660 ◽  
Author(s):  
Xiaoxing Xie ◽  
Gaoyun Xiong ◽  
Wenjun Chen ◽  
Hongdan Fu ◽  
Mingqian Li ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Nasopharyngeal Carcinoma ◽  
Cell Apoptosis ◽  
Inhibitory Effect ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Inhibitory Effects ◽  
Protein Levels ◽  
Flow Cytometric ◽  
Phosphoinositide 3 Kinase

FOXD3 has been found previously to positively regulate miR-26b, a tumor inhibitor of nasopharyngeal carcinoma (NPC). However, FOXD3’s precise function and associated mechanism of action in NPC have not yet been investigated. In this study, the expression of FOXD3 mRNA and protein was evaluated using RT-qPCR, western blotting, and immunohistochemistry. Protein levels involved in the phosphoinositide 3-kinase – protein kinase B (PI3K–Akt) pathway were assessed by western blot, and cell proliferation was determined by MTT and colony forming assays. Additionally, cell apoptosis was assessed by flow cytometric assay. Finally, the migration and invasion capabilities of the NPC cells were determined using wound healing and Transwell assays. We found that FOXD3 levels were relatively low in NPC tissue and cells, while an increase caused the inhibition of the PI3K–Akt pathway. Functional experiments found that overexpression of FOXD3 suppressed cell proliferation, migration, and invasion and enhanced cell apoptosis in NPC C6661 cells. IGF-1, an activator of the PI3K–Akt pathway, reversed the inhibitory effect of FOXD3. Furthermore, we found upregulation of the PI3K–Akt pathway and upregulation of the inhibitory effects of FOXD3 on C6661 cellular activities. In conclusion, FOXD3 negatively affected the PI3K–Akt pathway to restrain the processes involved in C6661 cell pathology. These findings further exposed the function and downstream axis of FOXD3 in NPC and displayed a promising new target for NPC therapy.

scholarly journals LINC01121 Inhibits Cell Apoptosis While Facilitating Proliferation, Migration, and Invasion Though Negative Regulation of the Camp/PKA Signaling Pathway via GLP1R

2018 ◽  
Vol 47 (3) ◽  
pp. 1007-1024 ◽  
Author(s):  
Yi-Gang Qian ◽  
Zhou Ye ◽  
Hai-Yong Chen ◽  
Zhen Lv ◽  
Ai-Bin Zhang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Microarray Data ◽  
Cell Apoptosis ◽  
Migration And Invasion ◽  
Protein Levels ◽  
Pancreatic Cancer Cells ◽  
Significant Difference

Background/Aims: Pancreatic cancer is an aggressive malignancy as a result of highly metastatic potential. The current study was carried out to alter the expression of LINC01121 in pancreatic cancer, with the aim of elucidating its effects on the biological processes of cell proliferation, migration, invasion, and apoptosis. We hypothesized that both the GLP1R gene and cAMP/PKA signaling pathway participate in the aforementioned process. Methods: Microarray data (GSE14245, GSE27890 and GSE16515) and annotating probe files linked to pancreatic cancer were downloaded through the GEO database. The Multi Experiment Matrix (MEM) site was used to predict the target gene of lncRNA. Both pancreatic cancer tissues (n = 56) and paracancerous tissues (n = 45) were collected from patients diagnosed with pancreatic cancer. Immunohistochemistry was applied to identify the positive expression rate of GLP1R protein. Isolated pancreatic cancer cells and PANC-1 cells were independently classified into the blank, negative control (NC), LINC01121 vector, siRNA-LINC01121, siRNA-GLP1R and siRNA-LINC01121 + siRNA-GLP1R groups. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were applied to detect the expressions of LINC01121, GLP1R, cAMP, PKA, CREB, Bcl-2, Bad and PCNA. Cell proliferation, migration, invasion, cycle progression, and apoptosis were examined by MTT assay, scratch test, Transwell assay and flow cytometry analyses of Annexin V-FITC/PI staining. Results: Observations were made indicating that LINC01121 was highly expressed, while low expressions of GLP1R in pancreatic cancer were detected based on microarray data, which was largely in consistent with the data collected of LINC01121 and GLP1R within the tissues. The target prediction program and luciferase activity analysis was testament to the notion suggesting that GLP1R was indeed a target of LINC01121. In contrast to the blank and NC groups, the LINC01121 vector group exhibited increased expressions of LINC01121; decreased mRNA and protein levels of GLP1R, Bad, cAMP, and PKA; increased protein levels of CREB, Bcl-2, PCNA, p-PKA and p-CREB; increased cell proliferation, migration and invasion; and decreased cell apoptosis. There was no significant difference detected among the blank, NC, and siRNA-LINC01121 + siRNA-GLP1R groups, except that decreased LINC01121 expression was determined in the siRNA-LINC01121 + siRNA-GLP1R group. Parallel data were observed in the pancreatic cancer cells and PANC-1 cells. Conclusion: The current study presents evidence indicating that LINC01121 might inhibit apoptosis while acting to promote proliferation, migration, and invasion of pancreatic cancer cells, supplementing the stance held that LINC01121 functions as a tumor promoter by means of its involvement in the process of translational repression of the GLP1R and inhibition of the cAMP/PKA signaling pathway.

scholarly journals LINC01128 expedites cervical cancer progression by regulating miR-383-5p/SFN axis

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yi Hu ◽  
Yan Ma ◽  
Jie Liu ◽  
Yanlin Cai ◽  
Mengmeng Zhang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Cell Apoptosis ◽  
High Expression ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Real Time Quantitative Pcr ◽  
Protein Levels ◽  
Normal Tissues

Abstract Background Cervical cancer (CC), causing significant morbidity and mortality worldwide, is one of the most common gynecological malignancies in women. SFN has been reported as a potential prognostic marker with apparent high expression in tumors. Nevertheless, the function mechanism of SFN is not clear yet in CC. Methods The relative expressions of RNAs were detected by real-time quantitative PCR (RT-qPCR). Colony formation assay, EdU stained assay and CCK-8 assay were to check cell proliferation ability in CC. Flow cytometry and apoptosis related proteins analysis were used to measure cells apoptosis capacity. Luciferase reporter assay and RNA pull down assay were to verify the molecular mechanism. Results SFN was highly expressed in CC tissues and CC cell lines compared with normal tissues and normal cell line. After interfering SFN, cell proliferation, migration and invasion ability was inhibited as well as cell apoptosis ability was promoted. In subsequence, miR-383-5p exhibited conspicuous low expression in CC tissues. And miR-383-5p was found to bind to SFN and have anti-cancerous effects in CC. Moreover, LINC01128 displayed remarkable high expression in CC tissues. Besides, LINC01128 shortage could reduce the expression of SFN at mRNA and protein levels. And the affinity between LINC01128 and miR-383-5p was verified. In the end, it was proved that LINC01128 could enhance cell proliferation, migration and invasion as well as inhibit cell apoptosis by binding with miR-383-5p and upregulating SFN. Conclusion LINC01128 expedited cells cellular process in CC by binding with miR-383-5p to release SFN. Graphical Abstract

scholarly journals MicroRNA-497-5p Functions as a Modulator of Apoptosis by Regulating Metadherin in Ovarian Cancer

2020 ◽  
Vol 29 ◽  
pp. 096368971989706 ◽  
Author(s):  
Chunyan Liu ◽  
Anne Bordeaux ◽  
Stanka Hettich ◽  
Suhui Han
Keyword(s):  
Ovarian Cancer ◽  
Mortality Rate ◽  
Molecular Mechanism ◽  
High Mortality ◽  
Cell Apoptosis ◽  
Untranslated Region ◽  
Protein Levels ◽  
Enhanced Expression ◽  
Related Proteins

Ovarian cancer (OC) has a high mortality rate among women worldwide. However, even with the advances in detection and therapeutics, the number of cases is increasing worldwide. Increasingly, microRNAs (miRNAs), including miR-497-5p, have been implicated in the progression of many cancers, but the role of miR-497-5p in OC remains unknown. The purpose of this study was to investigate the underlying molecular mechanism of miR-497-5p in OC. Herein, we find that miR-497-5p is down-regulated in OC tissues, and overexpression of miR-497-5p enhances apoptosis in OC cells. The increased apoptosis was correlated with enhanced expression of apoptosis-related proteins. MiR-497-5p directly bound the 3’-untranslated region of metadherin (MTDH), leading to the reduction of MTDH in mRNA and protein levels. Moreover, MTDH knockout promoted the apoptosis of OC cells. Taken together, we conclude that miR-497-5p contributes to cell apoptosis in OC by regulating MTDH.

scholarly journals Knockdown of Gab1 Inhibits Cellular Proliferation, Migration, and Invasion in Human Oral Squamous Carcinoma Cells

2018 ◽  
Vol 26 (4) ◽  
pp. 617-624 ◽  
Author(s):  
Luyong Xu ◽  
Jie Li ◽  
Zheng Kuang ◽  
Yan Kuang ◽  
Hong Wu
Keyword(s):  
Cell Lines ◽  
Cell Apoptosis ◽  
Cellular Proliferation ◽  
Squamous Carcinoma ◽  
Migration And Invasion ◽  
Western Blot Assay ◽  
Protein Levels ◽  
Squamous Carcinoma Cells ◽  
Oral Squamous Carcinoma ◽  
Proliferation And Invasion

Grb2-associated binder 1 (Gab1) is often aberrant in cancerous cells and tissues, whose alteration is responsible for aggressive phenotypes. In this study, we examined the Gab1 expression in human oral squamous cell carcinoma (OSCC) tissues and investigated the cellular and molecular effect of Gab1 on migration, invasion, and cell growth of the OSCC cell lines SCC15 and SCC25. We found that Gab1 was overexpressed in OSCC tissues and cells, which is related to the protein levels of various molecules associated with cellular proliferation, migration, and invasion. Functional assays identified that Gab1 overexpression promoted cell proliferation and invasion of OSCC cells and inhibited cell apoptosis in the SCC15 and SCC25 cell lines. On the other hand, Gab1 silencing affected the proliferation and invasion of OSCC cells and induced cell apoptosis. Western blot assay identified that Gab1 overexpression suppressed the expression of Cdc20 homolog 1 (Cdh1) and then promoted cell invasion in OSCC cells. Furthermore, Gab1-mediated Cdh1 downregulation was significantly reversed when the cells were subjected to an inhibitor of p-Akt. In conclusion, these results suggested that Gab1 induced malignant progression of OSCC cells probably via activation of the Akt/Cdh1 signaling pathway. Thus, Gab1 may be a potential therapeutic target in the treatment of OSCC patients.

scholarly journals Antitumor Effects of Dihydromyricetin on the Proliferation, Migration and Apoptosis of Human Hepatocellular Carcinoma Hep3B Cells

2021 ◽  
Author(s):  
Lianggui Jiang ◽  
Wen-Chu Ye ◽  
Zuobiao Li ◽  
Yongguang Yang ◽  
Wei Dai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Apoptosis ◽  
Public Health Problem ◽  
Migration And Invasion ◽  
High Morbidity ◽  
Caspase 9 ◽  
Antitumor Effects ◽  
Protein Levels ◽  
Mrna And Protein Expression ◽  
Hep3b Cells

Abstract Background: Hepatocellular carcinoma (HCC) represents a serious public health problem worldwide and has high morbidity and mortality. Dihydromyricetin (DHM) exhibits anti-tumor effect on a variety of malignancies, but its antitumor function of DHM in HCC has been unclear. The aim of this study was designed to investigate the antitumor effect of DHM on cell apoptosis, proliferation, migration and invasion of hepatoma carcinoma cells. Methods: Cultured Hep3B cells were treated with different DHM concentrations, follow by cell apoptosis, proliferation, migration and invasion were examined by CCK-8, colony formation assay, wound healing, Transwell and flow cytometry, respectively. The mRNA and protein expression of apoptosis-associated genes and Bcl-2/Caspase-9 signaling pathway were validated by RT-PCR and western blot. Results: DHM markedly suppressed proliferation, migration, invasion and facilitated apoptosis in Hep3B cells. Mechanistically, DHM significantly downregulated the Bcl-2 expression, and upregulated the mRNA and protein levels of Cleaved-Caspase 3, Cleaved- Caspase 9, Bak, Bax and Bad. Furthermore, in the nude mice tumorigenic model, DHM treatment greatly decreased the weight of the HCC tumors compared to the weights in control and NDP group. Conclusions: DHM could suppress cell proliferation, migration, invasion, and facilitated apoptosis in Hep3B cells. These findings could provide novel insights to develop potential therapeutic strategy for the clinical treatment of HCC.

scholarly journals PPARαLigands as Antitumorigenic and Antiangiogenic Agents

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
Ambra Pozzi ◽  
Jorge H. Capdevila
Keyword(s):  
Target Genes ◽  
Suppressor Gene ◽  
Migration And Invasion ◽  
Antiangiogenic Agents ◽  
Peroxisome Proliferator ◽  
Cell Functions ◽  
Obesity And Diabetes ◽  
Brown Adipose ◽  
Peroxisome Proliferator Activated Receptors ◽  
Ppar Ligands

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor family of ligand-activated transcription factors. This subfamily is composed of three members—PPARα, PPARδ, and PPARγ—that differ in their cell and tissue distribution as well as in their target genes. PPARαis abundantly expressed in liver, brown adipose tissue, kidney, intestine, heart, and skeletal muscle; and its ligands have been used to treat diseases such as obesity and diabetes. The recent finding that members of the PPAR family, including the PPARα, are expressed by tumor and endothelial cells together with the observation that PPAR ligands regulate cell growth, survival, migration, and invasion, suggested that PPARs also play a role in cancer. In this review, we focus on the contribution of PPARαto tumor and endothelial cell functions and provide compelling evidence that PPARαcan be viewed as a new class of ligand activated tumor “suppressor” gene with antiangiogenic and antitumorigenic activities. Given that PPAR ligands are currently used in medicine as hypolipidemic drugs with excellent tolerance and limited toxicity, PPARαactivation might offer a novel and potentially low-toxic approach for the treatment of tumor-associated angiogenesis and cancer.

Plantamajoside Inhibits Hepatic Carcinoma Cell Proliferation, Migration, Invasion and Induces Apoptosis Through Regulating Phosphatidylinositol-3-Kinase/ Protein Kinase B Pathway

2020 ◽  
Vol 10 (5) ◽  
pp. 662-668
Author(s):  
Yiqun Zhou ◽  
Yong Tan ◽  
Zheng Shi ◽  
Renshou Chen
Keyword(s):  
Cell Viability ◽  
Cell Apoptosis ◽  
Biological Activities ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Hepatic Carcinoma ◽  
Plantago Asiatica ◽  
Related Proteins ◽  
Hcc Cells

Background: Plantamajoside (PMS) is the main active compound of Plantago asiatica . It is a traditional Chinese medicine and has been reported to have various biological activities. However, the function of PMS on hepatic carcinoma cells (HCC) and the potential mechanism of action still remains unevaluated. Here, we investigated the effect of PMS on HCC cells and the potential molecular mechanism. Methods: Firstly, HCC cells were treated with different dose of PMS (0, 20, 80 and 160 g/ml). Then, cell viability was determined by MTT assay. Furthermore, we investigated the cell apoptosis, migration and invasion by flow cytometry assay and Transwell assay. In addition, PI3K/AKT related proteins p-AKT and AKT were determined via Western blotting assay. Results: Our results showed that PMS dose-dependently reduced HCC cell viability. PMS also induced HCC cell apoptosis, up-regulated the expression of Bax and down-regulated expression of Bcl-2. In addition, the Bcl-2/Bax ratio was also decreased. The migration and invasion of HCC cells were also consistently suppressed by PMS treatment in a dose-dependent manner. Subsequently, the results indicated that PMS down-regulated the expression of p-AKT, suggesting the inhibition of the PI3K/AKT pathway in HCC progression. Conclusion: The results indicated that PMS could inhibit HCC progression through regulating cell viability, apoptosis, migration, invasion and PI3K/AKT pathway. Thus, PMS might be a hopeful pharmacological agent for the treatment of hepatic carcinoma.

Taraxasterol inhibits TGF-β1-induced epithelial-to-mesenchymal transition in papillary thyroid cancer cells through regulating the Wnt/β-catenin signaling

2021 ◽  
pp. 096032712110237
Author(s):  
J Zhu ◽  
X Li ◽  
S Zhang ◽  
J Liu ◽  
X Yao ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Suppressive Effect ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Papillary Thyroid ◽  
Concentration Dependent Manner ◽  
Mesenchymal Transition ◽  
Tgf Β1

Taraxasterol (TAR) is a kind of active compound extracted from dandelion and its molecular structure resembles steroid hormones. Recently, TAR has been reported to show an anti-tumor activity. However, the specific role of TAR in papillary thyroid cancer (PTC) has not been clarified. In this study, we investigated the effect of TAR on PTC cell migration, invasion and epithelial-to-mesenchymal transition (EMT) induced by TGF-β1. PTC cells were exposed to TGF-β1 (5 ng/mL) and then treated with different concentrations of TAR. We found that TAR showed no obvious cytotoxicity below 10 μg/mL but notably reduced migration and invasion of TGF-β1-treated PTC cells. Moreover, TAR treatment decreased MMP-2 and MMP-9 levels, and obviously affected the expression of EMT markers. We also observed that Wnt3a and β-catenin levels were significantly increased in TGF-β1-treated PTC cells while TAR inhibited these effects in a concentration-dependent manner. Additionally, activation of the Wnt pathway by LiCl attenuated the suppressive effect of TAR on TGF-β1-induced migration, invasion and EMT in PTC cells. Taken together, we highlighted that TAR could significantly suppress TGF-β1-regulated migration and invasion by reversing the EMT process via the Wnt/β-catenin pathway, suggesting that TAR may be a potential anti-cancer agent for PTC treatment.

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