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Altered expression pattern of circular RNAs in metastatic oral mucosal melanoma.

ABSTRACT: Circular RNAs (circRNAs) are known to be associated with carcinogenesis, and can serve as potential biomarkers for cancer diagnosis and therapeutic implications. However, little is known about their expression patterns in oral mucosal melanoma (OMM), an extremely rare cancer that is distinct from cutaneous melanoma for its clinical course and prognosis. To investigate circRNAs expression profile in OMM, we performed a circRNAs microarray to analyze 6 primary OMM samples with lymph nodes dissemination, and constructed a genome-wide circRNA profile. Our results revealed that 90 circRNAs were significantly dysregulated in the metastatic OMM tissues when compared to the paired adjacent tissues. Among them, hsa_circ_0005320, hsa_circ_0067531, hsa_circ_0008042 were significantly upregulated in primary tumor and metastatic lymph nodes compared to paired adjacent normal tissues and non-metastatic lymph nodes, whereas the expression of hsa_circ_0000869 and hsa_circ_0000853 were downregulated relatively. Gene Ontology (GO) and pathway analyses of differentially expressed circRNAs indicated that these identified circRNAs might play important roles in protein modification, protein binding and cellular metabolism in metastatic OMM. Functions of several selected circRNA were also identified. In addition, by using bioinformatics predictions, we further demonstrated that hsa_circ_0005320, hsa_circ_0067531 and hsa_circ_0000869 could serve as competing endogenous RNA (ceRNA), which might regulate tumorigenesis and metastatic of OMM by binding to specific microRNAs. Our results not only suggested that circRNAs might play critical roles in metastasis of OMM, but also provided critical information of circRNAs in regulating OMM progression. The findings would help us to develop potential biomarkers for clinical diagnosis and design therapeutic strategies for OMM.

SUBMITTER: Ju H

PROVIDER: S-EPMC6176177 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Altered expression pattern of circular RNAs in metastatic oral mucosal melanoma.

Ju Houyu H Zhang Liming L Mao Lu L Liu Shuli S Xia Weiya W Hu Jingzhou J Ruan Min M Ren Guoxin G

American journal of cancer research 20180901 9

Circular RNAs (circRNAs) are known to be associated with carcinogenesis, and can serve as potential biomarkers for cancer diagnosis and therapeutic implications. However, little is known about their expression patterns in oral mucosal melanoma (OMM), an extremely rare cancer that is distinct from cutaneous melanoma for its clinical course and prognosis. To investigate circRNAs expression profile in OMM, we performed a circRNAs microarray to analyze 6 primary OMM samples with lymph nodes dissemin ...[more]

PMID: 30323971

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Project description: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.

Dataset Information

Altered expression pattern of circular RNAs in metastatic oral mucosal melanoma.

Publications

Altered expression pattern of circular RNAs in metastatic oral mucosal melanoma.

Similar Datasets

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