scholarly journals Microarray profile of circular RNAs identifies hsa_circRNA_102459 and hsa_circRNA_043621 as important regulators in oral squamous cell carcinoma

Author(s):  
Wei Deng ◽  
Wei Peng ◽  
Tao Wang ◽  
Jingxin Chen ◽  
Xunding Qiu ◽  
...  
2018 ◽  
Vol 47 (6) ◽  
pp. 2511-2521 ◽  
Author(s):  
Si-Yu Zhao ◽  
Jun Wang ◽  
Shao-Bo Ouyang ◽  
Zi-Kun Huang ◽  
Lan Liao

Background/Aims: Recent studies have demonstrated that circular RNAs (circRNAs) can serve as potential molecular markers for disease diagnosis. However, little is known about their diagnostic potential for oral squamous cell carcinoma (OSCC). This study aimed to determine the expression of circRNAs in the saliva of OSCC patients to identify novel biomarkers for OSCC screening. Methods: Microarray screening of circRNA was performed to identify differentially expressed circRNAs in saliva from 3 OSCC patients compared with 3 healthy controls. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the results, and the association between these confirmed salivary circRNAs and clinicopathological features was analyzed using the chi-squared test. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of the circRNAs identified. Preoperative expression and postoperative expression (1 month after the surgery) of hsa_circ_0001874 and hsa_circ_0001971 was also determined. Results: Our results indicated 12 upregulated and 20 downregulated circRNAs in the saliva from the OSCC patients compared with that from the healthy controls. Among the differentially expressed circRNAs, hsa_circ_0001874, hsa_circ_0001971, and hsa_circ_0008068 were upregulated and hsa_circ_0000140, hsa_circ_0002632, and hsa_circ_0008792 were downregulated in the OSCC group versus the healthy group. Clinical data indicated that salivary hsa_circ_0001874 was correlated with TNM stage (P=0.006) and tumor grade (P=0.023) and that hsa_circ_0001971 was correlated with TNM stage (P=0.019). The combination of hsa_circ_0001874 and hsa_circ_0001971 showed an area under the ROC curve of 0.922 (95% confidence interval, 0.883-0.961; P< 0.001). The risk score based on the combination of hsa_circ_0001874 and hsa_circ_0001971 also discriminated patients with OSCC from patients with oral leukoplakia (P< 0.001). Moreover, the expression levels of salivary hsa_circ_0001874 and hsa_circ_0001971 were clearly decreased in the postoperative samples compared with preoperative samples (P< 0.001). Conclusions: This is the first study to demonstrate the potential of salivary hsa_circ_0001874 and hsa_circ_0001971 as biomarkers for the diagnosis of OSCC.


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.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Feng Qiu ◽  
Bin Qiao ◽  
Nan Zhang ◽  
Zheng Fang ◽  
Lu Feng ◽  
...  

Abstract Background Circular RNAs (circRNAs) could participate in cis-dichlorodiammineplatinum (DDP) resistance of human cancers. However, circRNAs role in DDP resistance of oral squamous cell carcinoma (OSCC) progression remains largely undeveloped. Here, we attempted to explore the role of circ-SCMH1 (ID hsa_circ_0011946) in acquired DDP resistance. Methods Expression of circ-SCMH1, microRNA (miR)-338-3p and Lin-28 homolog B (LIN28B) was detected by real-time quantitative PCR and western blotting, and their interactions were confirmed by dual-luciferase reporter assay, RNA immunoprecipitation and RNA pull-down assay. DDP resistance was assessed by MTT assay, colony formation assay, flow cytometry, transwell assays, western blotting, and xenograft experiment. Transmission electron microscopic analysis, nanoparticle tracking analysis and western blotting confirmed the characterizations of extracellular vesicles (EVs). Results Circ-SCMH1 was upregulated in DDP-resistant OSCC tissues and cells (SCC-15/DDP and CAL-27/DDP). Circ-SCMH1 knockdown suppressed the half-maximal inhibitory concentration of DDP, colony formation, and migration/invasion in SCC-15/DDP and CAL-27/DDP cells, but promoted apoptosis rate and apoptotic proteins (Bax and cleaved-caspase-3) expression. However, silencing miR-338-3p abrogated above effects, and overexpressing miR-338-3p mimicked that. Similarly, miR-338-3p overexpression role could be counteracted by restoring LIN28B. Moreover, interfering circ-SCMH1 retarded tumor growth of SCC-15/DDP cells in vivo with DDP treatment or not. Mechanistically, circ-SCMH1 directly sponged miR-338-3p in regulating LIN28B, a target gene for miR-338-3p. Notably, circ-SCMH1 was an EVs cargo, and DDP-resistant OSCC cells-derived EVs could provoke circ-SCMH1 upregulation in parental cells. Conclusion Circ-SCMH1 contributes to chemoresistance of DDP-resistant OSCC cells partially via EVs secretion and circ-SCMH1/miR-338-3p/LIN28B axis.


2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Shuai Sun ◽  
Bowen Li ◽  
Yufan Wang ◽  
Xiang Li ◽  
Panpan Wang ◽  
...  

Background. Circular RNAs (circRNAs) are a type of covalently closed loop structure of endogenous RNAs. Recent studies have shown that circular RNAs may play an important role in human cancer. However, there is limited information on the function of circRNA in oral squamous cell carcinoma (OSCC). Methods. Hsa_circ_001242 expression levels in 40 paired OSCC tissues and four OSCC cell lines were selected using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of hsa_circ_001242 in OSCC. Results. Hsa_circ_001242 was significantly downregulated in OSCC tissues compared to paired adjacent normal tissues (P<0.001). Hsa_circ_001242 expression levels were significantly downregulated in four OSCC cell lines (SCC-9, SCC-15, SCC25, and CAL-27) than in human normal oral keratinocyte (HOK) cell lines. Moreover, the expression level of hsa_circ_001242 was negatively correlated with tumor size and T stage (P<0.05). The area under the ROC curve was 0.784. Conclusion. This study showed that hsa_circ_001242 was significantly downregulated in OSCC and may act as a potential novel biomarker for the diagnosis and treatment of OSCC.


2020 ◽  
Vol 48 (9) ◽  
pp. 030006052093688
Author(s):  
Hanyu Zhang ◽  
Yuehong Shen ◽  
Biru Zhang ◽  
Min Qian ◽  
Ying Zhang ◽  
...  

Objective Increasing evidence suggests that circular RNAs (circRNAs) play a major role in tumorigenesis and cancer progression. This study aimed to identify aberrant expression of hsa_circ_0003829 in oral squamous cell carcinoma (OSCC) and to explore its clinical significance. Methods We conducted a prospective clinical study to examine the expression pattern of hsa_circ_0003829 in 60 paired OSCC and normal clinical samples and in cell lines using real-time quantitative polymerase chain reaction. We also evaluated the diagnostic value of hsa_circ_0003829 in OSCC based on receiver operating characteristic (ROC) curve analysis, and examined the relationships between hsa_circ_0003829 expression and clinicopathological features in patients with OSCC. We further used bioinformatics software CircInteractome ( https: //Circinteractome.nia.nih.gov/ ) to predict circRNA–microRNA interactions. Results Hsa_circ_0003829 was significantly downregulated in OSCC compared with adjacent normal tissues. The area under the ROC curve was 0.81. Low expression levels of hsa_circ_0003829 in OSCC tissues were negatively correlated with lymph node metastasis status and TNM stage. Conclusions Downregulated expression of has_circ_0003829 suggests that this may be a key circRNA in OSCC, and may serve as a prospective biomarker for the diagnosis of OSCC.


2021 ◽  
Vol 11 ◽  
Author(s):  
Jie Yang ◽  
Xing-Hua Cao ◽  
Ke-Feng Luan ◽  
Yun-Dong Huang

Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy with increasing mortality and high recurrence. Ferroptosis is an emerging programed cell death and plays an essential role in tumorigenesis. Circular RNAs (circRNAs) have been reported as a type of critical regulators in OSCC development. In this study, we identified the function of circular RNA FNDC3B (circFNDC3B) in regulating ferroptosis during the malignant progression of OSCC. Our data demonstrated that the silencing of circFNDC3B by shRNA inhibited GPX4 and SLC7A11 expression and enhanced ROS, iron, and Fe2+ levels in OSCC cells. CircFNDC3B knockdown reinforced erastin-induced inhibitory effect on OSCC cells. The depletion of circFNDC3B repressed cell proliferation and enhanced cell apoptosis of OSCC cells. Mechanically, circFNDC3B was able to increase SLC7A11 by targeting miR-520d-5p. The overexpression of SLC7A11 reversed circFNDC3B depletion or miR-520d-5p-induced ferroptosis phenotypes of OSCC cells. Moreover, tumorgenicity assays in nude mice showed that the depletion of circFNDC3B repressed OSCC cell growth in vivo. Taken together, we concluded that circFNDC3B attenuated ferroptosis of OSCC cells and contributed to OSCC progression by regulating the miR-520d-5p/SLC7A11 axis. CircFNDC3B, miR-520d-5p, and SLC7A11 may serve as potential therapeutic targets of OSCC.


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.


2021 ◽  
Author(s):  
Qing Lu ◽  
Yanhai Che ◽  
Hongze Che ◽  
Min Hu

Abstract BackgroundA number of non-coding circular RNAs (circRNAs) have recently been implicated in the modulation of gene expression in cancer models. We therefore sought to explore if circZNF236 has a role in oral squamous cell carcinoma (OSCC).MethodsWe first examined circZNF236 expression in 32 pairs of OSCC and noncancerous tissues. We then investigated a functional role for circZNF236 using knockdown and overexpression approaches in OSCC cancer cell lines. Cell counting kit-8, wound healing, Transwell, and flow cytometry were employed to assess circZNF236 function in vitro. The association between circZNF236 and miR-145-5p, or that between miR-145-5p and malignant brain tumour domain containing 1 (MBTD1) was predicted by bioinformatics and demonstrated by dual-luciferase reporter assays, RNA pull-down assays as well as RNA immunoprecipitation (RIP) assays. A mouse OSCC xenograft model was employed to demonstrate the impacts of circZNF236 inhibition on tumor development in vivo. ResultsOSCC tissues and cells had higher levels of circZNF236 expression compared with normal controls. Furthermore, high circZNF2361 levels in patients with OSCC correlated with a poor prognosis. CircZNF236 silencing decreased the malignant properties of OSCC cells and suppressed OSCC tumor formation in the mouse model. We then noticed that miR-145-5p can be regulated by circZNF236, and that circZNF2361 promoted OSCC development by absorbing miR-145-5p and consequently upregulating MBTD1 expression.ConclusionCircZNF236 modulates OSCC via an miR-145-5p/MBTD1 axis. These results support the potential of circZNF236 as a treatment target for OSCC.


2021 ◽  
pp. 1-9
Author(s):  
Hanyu Zhang ◽  
Biru Zhang ◽  
Ying Zhang ◽  
Min Qian ◽  
Yuehong Shen ◽  
...  

BACKGROUND: As a novel class of endogenous ncRNAs, Circular RNAs (circRNAs) have been verified to be involved in the carcinogenesis and tumor progression. OBJECTIVE: This study aimed to investigate the potential function of a candidate circRNA hsa_circ_0036988 in oral squamous cell carcinoma (OSCC). METHODS: The altered expression of hsa_circ_0036988 was validated by quantitative real-time polymerase chain reaction (qRT-PCR) in OSCC samples and OSCC cell lines. The associations between the levels of hsa_circ_0036988 and the clinicopathological features were statistically analysed. The function of hsa_circ_0036988 in OSCC were evaluated via a series of in vitro experiments by using constructed plasmids or siRNA. Western blotting assays were conducted to evaluate changes in protein expression levels. RESULTS: Hsa_circ_0036988 was significantly downregulated in OSCC tissues compared with adjacent normal tissues. While low expression of hsa_circ_0036988 was highly correlated with lymph nodes metastasis. Overexpression or knockdown of hsa_circ_0036988 significantly affected the proliferation, migration and invasion of OSCC cells. Furthermore, the altered expression of hsa_circ_0036988 have an impact on the epithelial-to-mesenchymal transition (EMT)-related protein expression levels. CONCLUSIONS: Our findings indicated that hsa_circ_0036988 may affect cell proliferation, migration and invasion by regulating EMT progress, which might provide a therapeutic strategy for the treatment of OSCC.


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