scholarly journals The Emerging Role of Exosomes in Oral Squamous Cell Carcinoma

Author(s):  
Yanhui Lu ◽  
Zhichao Zheng ◽  
Yunyi Yuan ◽  
Janak L. Pathak ◽  
Xuechao Yang ◽  
...  

Oral cancer constitutes approximately 2% of all cancers, while the most common type, oral squamous cell carcinoma (OSCC) represents 90% of oral cancers. Although the treatment of OSCC has improved recently, it still has a high rate of local recurrence and poor prognosis, with a 5-year survival rate of only 50%. Advanced stage OSCC tends to metastasize to lymph nodes. Thus, exploring new therapeutic strategies for OSCC is therefore an urgent priority. Exosomes, the small membrane vesicles derived from endosomes, have been detected in a wide array of bodily fluids. Exosomes contain a diversity of proteins, mRNAs, and non-coding RNAs, including microRNAs, long non-coding RNAs, piRNAs, circular RNAs, tsRNAs, and ribosomal RNAs, which are delivered to neighboring cells or even transported to distant sites. Exosomes have been associated with the tumorigenesis of OSCC, promote the proliferation, colonization, and metastasis of OSCC by transferring their contents to the target cells. Furthermore, exosomes are involved in the regulation of the tumor microenvironment to transform conditions favoring cancer progression in vivo. In this review, we summarize the crucial role of exosomes in the tumorigenesis and progression of OSCC and discuss the potential clinical application of exosomes in OSCC treatment.

2019 ◽  
Vol 20 (22) ◽  
pp. 5779 ◽  
Author(s):  
Kiyofumi Takabatake ◽  
Tsuyoshi Shimo ◽  
Jun Murakami ◽  
Chang Anqi ◽  
Hotaka Kawai ◽  
...  

Sonic hedgehog (SHH) and its signaling have been identified in several human cancers, and increased levels of SHH expression appear to correlate with cancer progression. However, the role of SHH in the tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC) is still unclear. No studies have compared the expression of SHH in different subtypes of OSCC and focused on the relationship between the tumor parenchyma and stroma. In this study, we analyzed SHH and expression of its receptor, Patched-1 (PTCH), in the TME of different subtypes of OSCC. Fifteen endophytic-type cases (ED type) and 15 exophytic-type cases (EX type) of OSCC were used. H&E staining, immunohistochemistry (IHC), double IHC, and double-fluorescent IHC were performed on these samples. ED-type parenchyma more strongly expressed both SHH and PTCH than EX-type parenchyma. In OSCC stroma, CD31-positive cancer blood vessels, CD68- and CD11b-positive macrophages, and α-smooth muscle actin-positive cancer-associated fibroblasts partially expressed PTCH. On the other hand, in EX-type stroma, almost no double-positive cells were observed. These results suggest that autocrine effects of SHH induce cancer invasion, and paracrine effects of SHH govern parenchyma-stromal interactions of OSCC. The role of the SHH pathway is to promote growth and invasion.


2019 ◽  
Vol 39 (9) ◽  
Author(s):  
Xiaohui Duan ◽  
Na Shen ◽  
Jie Chen ◽  
Jing Wang ◽  
Qinghua Zhu ◽  
...  

Abstract Laryngeal squamous cell carcinoma (LSCC) is a common aggressive head and neck cancer. Circular RNAs (circRNAs) are implicated in numerous physiological and pathological processes, including tumorigenesis. The present study aimed to investigate the expression profile and biological role of circMYLK in LSCC. We found that circMYLK was highly expressed in LSCC tissues and cell lines. circMYLK overexpression promoted LSCC cell proliferation and G1/S cell cycle transition; whereas circMYLK knockdown had the contrary effects. Mechanistically, circMYLK can serve as a competing endogenous RNA for miR-195 to increase cyclin D1 expression in LSCC, and rescue experiments further showed that restoration of miR-195 could block the oncogenic role of circMYLK in LSCC. In conclusion, our findings indicate that the circMYLK/miR-195/cyclin D1 regulatory axis could affect the proliferation and cell cycle progression of LSCC cells, and may provide a novel therapeutic target for the treatment of LSCC.


2020 ◽  
Vol 10 ◽  
Author(s):  
Yanxiong Shao ◽  
Yuhan Song ◽  
Siming Xu ◽  
Siyi Li ◽  
Haiwen Zhou

BackgroundCircular RNAs (circRNAs) are involved in the pathogenesis of several diseases. Among oral maxillofacial cancers, oral squamous cell carcinoma (OSCC) has the highest incidence. However, the role of circRNAs in OSCC is still not clear. The aim of our study was to evaluate the circRNA expression profile in OSCC and explore further the potential role of circRNAs in the pathogenesis of OSCC.MethodsCircRNA sequencing was performed in 6 pairs of samples of OSCC and normal oral mucosal tissues. Expression of selected circRNAs was validated by qRT-PCR. GO and KEGG analyses were performed and binding relationships between circRNAs and miRNAs were predicted. The hsa_circ_0001766/miR-877-3p/VEGFA axis was selected to further elucidate its role in OSCC.ResultsWe showed that there were 122 differentially expressed (DE) circRNAs. Eight out of 10 selected circRNAs were validated by qRT-PCR. GO and KEGG analyses indicated that the identified DE circRNAs might be involved in the progression of OSCC. Then, after identification by Sanger sequencing and RNase R assay, the upregulated hsa_circ_0001766 was selected to investigate its potential role in OSCC. Bioinformatics analysis showed that hsa_circ_0001766 might act as a competing endogenous RNA (ceRNA) that sponged miR-877-3p to upregulate VEGFA expression. We selected OSCC cell lines SCC9 and SCC25. PCR results showed that the expression of hsa_circ_0001766 and VEGFA was upregulated in SCC9 and SCC25. Subsequently, using western blot, PCR, CCK8, and colony formation assays, we found that knocking down circRNA0001766 inhibited the expression of VEGFA and the proliferation of OSCC cells. Following this, miR-877-3p inhibitor reversed the inhibitory effect of si-hsa_circ_0001766 on expression of VEGFA and proliferation of OSCC cells.ConclusionsIn conclusion, our study revealed the possible role of circRNAs in the pathogenesis of OSCC, and identified the potential role of the hsa_circ_0001766/miR-877-3p/VEGFA axis in OSCC progression.


Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6152
Author(s):  
Yomna S. Abd El-Aziz ◽  
Lionel Y. W. Leck ◽  
Patric J. Jansson ◽  
Sumit Sahni

Autophagy is a cellular catabolic process, which is characterized by degradation of damaged proteins and organelles needed to supply the cell with essential nutrients. At basal levels, autophagy is important to maintain cellular homeostasis and development. It is also a stress responsive process that allows the cells to survive when subjected to stressful conditions such as nutrient deprivation. Autophagy has been implicated in many pathologies including cancer. It is well established that autophagy plays a dual role in different cancer types. There is emerging role of autophagy in oral squamous cell carcinoma (OSCC) development and progression. This review will focus on the role played by autophagy in relation to different aspects of cancer progression and discuss recent studies exploring the role of autophagy in OSCC. It will further discuss potential therapeutic approaches to target autophagy in OSCC.


2019 ◽  
Vol 21 (1) ◽  
pp. 258 ◽  
Author(s):  
Qingqing Feng ◽  
Hongli Zhang ◽  
Denglin Yao ◽  
Wei-Dong Chen ◽  
Yan-Dong Wang

Esophageal squamous cell carcinoma (ESCC) is a highly prevalent tumor and is associated with ethnicity, genetics, and dietary intake. Non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs) have been reported as functional regulatory molecules involved in the development of many human cancers, including ESCC. Recently, several ncRNAs have been detected as oncogenes or tumor suppressors in ESCC progression. These ncRNAs influence the expression of specific genes or their associated signaling pathways. Moreover, interactions of ncRNAs are evident in ESCC, as miRNAs regulate the expression of lncRNAs, and further, lncRNAs and circRNAs function as miRNA sponges to compete with the endogenous RNAs. Here, we discuss and summarize the findings of recent investigations into the role of ncRNAs (miRNAs, lncRNAs, and circRNAs) in the development and progression of ESCC and how their interactions regulate ESCC development.


Author(s):  
Asmaa Ali Hussein

Squamous cell carcinoma characterized by poor prognosis due to aggressive tumor growth and dissemination high rate of tumor cell . age ranged of patient case included in the study 40-62 years and mean age 55±99. The sex distribution male/female ratio 1:1. Male case 15 and female 15 of the present study The results of clinical forums showed in the current study was endophytic 10(33.3%) in the same time Exophytic were presented in 20 cases (76.7%). Regarding distribution of the tumors site, the preponderance of them 19 cases 73.3% were located alveolar mucosa, followed by in the tongue 11 cases(36.7%) Tumor stage was analyzed and recorded in Oral squamous cell carcinoma included cases, the preponderance of them were Stage II 11 cases 36.7% followed by stage III 10 cases 33.3% , 9 cases 30.0% were stage I. While Concerning tumor grade, majority of them 15 cases 50% had grade II moderately differentiated SCC, while 11 cases 36.7% had grade III poorly differentiated SCC and 4 cases 13.3% had grade I well differentiated SCC Positive TGF-β3 immunostaining was detected as cell with staining brown color, all tissues sections included show Positive expression based on IHC teqnique. Positive Transforming Growth Factor TGF-β3 Immuno staining was found in all case results and display that 4 samples with percentage 13.3% expressed strong positive 87.67 ± 1.45 expression , 11cases 36.7% showed 51.33 ±0.88 positive expression moderate at the same time 15 samples 50.0% showed positive weak expression.


2020 ◽  
Vol 40 (12) ◽  
pp. 6987-6995
Author(s):  
NORBERT NECKEL ◽  
MARCO MICHAEL ◽  
DANIEL TROELTZSCH ◽  
JONAS WÜSTER ◽  
STEFFEN KOERDT ◽  
...  

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ling Mao ◽  
Xiaoweng Wu ◽  
Zhengpeng Gong ◽  
Ming Yu ◽  
Zhi Huang

Abstract Background/objective Accumulated evidence has demonstrated that aerobic glycolysis serves as a regulator of tumor cell growth, invasion, and angiogenesis. Herein, we explored the role of protein disulfide isomerase family 6 (PDIA6) in the aerobic glycolysis and the progression of oral squamous cell carcinoma (OSCC). Methods The expression pattern of PDIA6 in OSCC tissues was determined by qPCR and western blotting. Lentivirus and small interfering RNAs (siRNAs) were introduced into cells to upregulate and downregulate PDIA6 expression. CCK-8, flow cytometry, transwell, and xenotransplantation models were applied to detect cell proliferation, apoptosis, migration, invasion, and tumorigenesis, respectively. Results A high expression pattern of PDIA6 was observed in OSCC tissues, which was closely associated with lower overall survival and malignant clinical features in OSCC. Compared with the control group, overexpression of PDIA6 induced significant enhancements in cell growth, migration, invasiveness, and tumorigenesis and decreased cell apoptosis, while knockdown of PDIA6 caused opposite results. In addition, overexpression of PDIA6 increased glucose consumption, lactate production, and ATP level in OSCC cells. Conclusion This study demonstrated that PDIA6 expression was elevated in OSCC tissues, and overexpression of it promoted aerobic glycolysis and OSCC progression.


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