scholarly journals Oral squamous cell carcinoma (OSCC)-derived exosomal MiR-221 targets and regulates phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) to promote human umbilical vein endothelial cells migration and tube formation

Bioengineered ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 2164-2174
Author(s):  
Shuqi He ◽  
Wu Zhang ◽  
Xian Li ◽  
Junjie Wang ◽  
Xufeng Chen ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Endothelial Cells ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Regulatory Subunit ◽  
Phosphoinositide 3 Kinase ◽  
Umbilical Vein Endothelial Cells

scholarly journals Suppression of Angiogenesis by Targeting Cyclin-Dependent Kinase 7 in Human Umbilical Vein Endothelial Cells and Renal Cell Carcinoma: An In Vitro and In Vivo Study

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1469 ◽  
Author(s):  
Chung-Sheng Shi ◽  
Kuan-Lin Kuo ◽  
Mei-Sin Chen ◽  
Po-Ming Chow ◽  
Shing-Hwa Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Endothelial Cells ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Antitumor Effects ◽  
Angiogenic Activity ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Cancer cells rely on aberrant transcription for growth and survival. Cyclin-dependent kinases (CDKs) play critical roles in regulating gene transcription by modulating the activity of RNA polymerase II (RNAPII). THZ1, a selective covalent inhibitor of CDK7, has antitumor effects in several human cancers. In this study, we investigated the role and therapeutic potential of CDK7 in regulating the angiogenic activity of endothelial cells and human renal cell carcinoma (RCC). Our results revealed that vascular endothelial growth factor (VEGF), a critical activator of angiogenesis, upregulated the expression of CDK7 and RNAPII, and the phosphorylation of RNAPII at serine 5 and 7 in human umbilical vein endothelial cells (HUVECs), indicating the transcriptional activity of CDK7 may be involved in VEGF-activated angiogenic activity of endothelium. Furthermore, through suppressing CDK7 activity, THZ1 suppressed VEGF-activated proliferation and migration, as well as enhanced apoptosis of HUVECs. Moreover, THZ1 inhibited VEGF-activated capillary tube formation and CDK7 knockdown consistently diminished tube formation in HUVECs. Additionally, THZ1 reduced VEGF expression in human RCC cells (786-O and Caki-2), and THZ1 treatment inhibited tumor growth, vascularity, and angiogenic marker (CD31) expression in RCC xenografts. Our results demonstrated that CDK7-mediated transcription was involved in the angiogenic activity of endothelium and human RCC. THZ1 suppressed VEGF-mediated VEGFR2 downstream activation of angiogenesis, providing a new perspective for antitumor therapy in RCC patients.

scholarly journals LncRNA FENDRR in Carcinoma-Associated Fibroblasts Regulates the Angiogenesis of Oral Squamous Cell Carcinoma Through the PI3K/AKT Pathway

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuming Xu ◽  
Erhui Jiang ◽  
Zhe Shao ◽  
Zhengjun Shang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Umbilical Vein ◽  
Quantitative Polymerase Chain Reaction ◽  
Inhibitory Effect ◽  
Akt Pathway ◽  
Normal Tissues ◽  
Carcinoma Associated Fibroblasts

Angiogenesis is essential for the development of tumors. Studies have shown that carcinoma-associated fibroblasts (CAFs) are involved in regulating tumor angiogenesis, but the mechanism remains unclear. Recently, long noncoding RNAs (lncRNAs) have been proved to play an important role in the angiogenesis of various tumors. However, there is currently no research involving the regulation of CAFs on the angiogenesis of oral squamous cell carcinoma (OSCC) mediated by lncRNAs. By analyzing microarray data, we identified that the expression of lncRNA FOXF1 adjacent noncoding developmental regulatory RNA (FENDRR) in OSCC patients is downregulated, compared to that in normal tissues. Quantitative polymerase chain reaction (qPCR) results demonstrated that FENDRR expression is lower in CAFs compared to normal fibroblasts (NFs) of OSCC patients. KEGG pathway analysis revealed that some genes differentially expressed between CAFs and NFs of HNSCC patients are enriched to the PI3K/AKT pathway. Further experiments confirmed that the downregulation of FENDRR can activate the PI3K/AKT pathway in NFs and enhances the expression of matrix metalloproteinase 9 (MMP9). The overexpression of FENDRR had the opposite effect. Besides, we co-cultured human umbilical vein endothelial cells (HUVECs) with CAFs, and the tube-forming ability of HUVECs co-cultured with CAFs overexpressing FENDRR decreased significantly. However, activation of the AKT pathway of CAFs overexpressing FENDRR can weaken the inhibitory effect of FENDRR on angiogenesis. In summary, our experiments are focused on the influence of lncRNAs in CAFs on OSCC angiogenesis for the first time and prove that FENDRR mediates CAFs’ regulation of OSCC angiogenesis through the PI3K/AKT pathway.

scholarly journals Exosomal miR-130b-3p Promotes Progression and Tubular Formation Through Targeting PTEN in Oral Squamous Cell Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Wei Yan ◽  
Yuping Wang ◽  
Yong Chen ◽  
Yanjun Guo ◽  
Qiang Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Umbilical Vein ◽  
Negative Regulator ◽  
High Rate ◽  
Mice Model ◽  
Tubular Formation

Oral squamous cell carcinoma (OSCC), accounting for two-thirds of head and neck cancer, is characterized by poor prognosis and a high rate of mortality. Exosomes have emerged as potential molecule-shuttle in intercellular communication, thereby regulating the physiological processes of recipient cells. To date, the effect of exosomal microRNAs (miRNAs) on the progression of OSCC has not been fully investigated. In this study, we found that the protein, but not mRNA expression of Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was decreased in OSCC. The results revealed that miR-130b-3p was an important negative regulator for PTEN expression. Additionally, overexpression and knockdown of miR-130b-3p enhanced and inhibited angiogenesis in human umbilical vein endothelial cells (HUVECs), respectively. Also, miR-130b-3p was transferred by exosomes to HUVECs and then promoted angiogenesis and inhibit the expression of PTEN. Furthermore, exosomal miR-130b-3p derived from OSCC cells promoted tumor growth and blood vessel formation in the xenograft mice model. Taken together, we demonstrated that exosome-mediated miR-130b-3p promoted progression and tubular formation in OSCC in vitro and in vivo. These results would provide new insight into exploring biomarkers and effective therapeutic strategies for OSCC.

Inhibition of Angiogenesis and Tumor Progression of Mk-0429, an Integrin Αvβ3 Antagonist, on Oral Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Takayuki Nakagawa ◽  
Kouji Ohta ◽  
Takako Naruse ◽  
Miyuki Sakuma ◽  
Satoshi Okuda ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Cancer ◽  
Oral Squamous Cell Carcinoma ◽  
Tumor Progression ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tube Formation ◽  
Dependent Manner ◽  
Dose Dependent

Abstract PurposeIntegrin αvβ3 is an essential molecule for tumor angiogenesis. This study aimed to investigate the anti-tumor effect of MK-0429, an integrin αvβ3 antagonist, on oral squamous cell carcinoma (OSCC) through its inhibitory effect on angiogenesis.MethodsIn this study, we investigated the effect of MK-0429 on cellular function and angiogenesis in vitro with the use of an immortalized human umbilical vein endothelial cell, HUEhT-1, which is immortalized by the electroporatic transfection of hTERT. The effect of MK-0429 on the integrin αvβ3 signaling pathway was examined by FAK and ERK 1/2 phosphorylation. The anti-angiogenic effect of MK-0429 was evaluated by in vitro tube formation assay. The anti-tumor effect on OSCC was assessed by administrating MK-0429 to mouse oral cancer xenografts.ResultsMK-0429 inhibited cell proliferation, migration, and adhesion of HUEhT-1 in a dose-dependent manner. FAK and ERK phosphorylation were significantly blocked by MK-0429 treatment. Tube formation was suppressed by MK-0429 in dose-dependent manner. Tumor progression was significantly suppressed by MK-0429 administration in mouse oral cancer xenografts. Histological study revealed that MK-0429 decreased tumor vascularization.ConclusionThese results indicated integrin αvβ3 as a therapeutic target for OSCC and suggested that MK-0429 might be clinically applicable as an anti-tumor agent with potent antiangiogenic activity.

Role of Clinical Palpation in Evaluation of Cervical Lymph Node in Oral Squamous Cell Carcinoma

2013 ◽  
Vol 1 (2) ◽  
pp. 02-06
Author(s):  
SM Anwar Sadat ◽  
Sufia Nasrin Rita ◽  
Shoma Banik ◽  
Md Nazmul Hasan Khandker ◽  
Md Mahfuz Hossain ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Lymph Node ◽  
Oral Squamous Cell Carcinoma ◽  
Lymph Nodes ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Predictive Value ◽  
Cervical Lymph Node ◽  
Betel Quid ◽  
Cervical Lymph Nodes

A cross sectional study of 29 cases of oral squamous cell carcinoma with or without  cervical lymph node metastasis was done among Bangladeshi patients from January 2006 to December 2007. Majority of the study subjects (34.5%) belonged to the age group of 40-49 years. 58.6% of the study subjects were male, while remaining 41.4% of them were female. 51.7% of the lesions were located in the alveolar ridge where the other common sites were buccal mucosa (27.6%) and retro molar area (13.8%). Half of the study subjects (51.7%) were habituated to betel quid chewing followed by 37.9% and 10.3% were habituated to smoking and betel quid-smoking respectively. Grade I lesions was most prevalent (75.9%) in the study subjects.  Majority of cases presented with Stage IV lesions (55.2%). The sensitivity, specificity, positive predictive value, negative predictive value & accuracy of clinical palpation method for determining metastatic cervical lymph nodes were 93.33%, 64.29%, 73.68%, 90% and 79.3% respectively. Careful and repeated clinical palpation plays important role in evaluation of cervical lymph nodes though several modern techniques may help additionally in the management of oral cancer.DOI: http://dx.doi.org/10.3329/updcj.v1i2.13978 Update Dent. Coll. j. 2011: 1(2): 02-06

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