Bioinformatics identification of the candidate microRNAs and construction of a competing endogenous RNA regulatory network in lacrimal gland adenoid cystic carcinoma high-grade transformation

Meixia Jiang; Xun Liu; Chuanli Zhang; Limin Zhu; Hai-Dong Wu; Lijie Dong; Tingting Wang; Tingting Lin; Yanjin He

doi:10.3892/ol.2021.12621

Bioinformatics identification of the candidate microRNAs and construction of a competing endogenous RNA regulatory network in lacrimal gland adenoid cystic carcinoma high-grade transformation

Oncol Lett. 2021 May;21(5):360. doi: 10.3892/ol.2021.12621. Epub 2021 Mar 8.

Authors

Meixia Jiang¹, Xun Liu¹, Chuanli Zhang¹, Limin Zhu¹, Hai-Dong Wu², Lijie Dong¹, Tingting Wang¹, Tingting Lin¹, Yanjin He¹

Affiliations

¹ Tianjin International Joint Research and Development Centre of Ophthalmology and Vision Science, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin 300384, P.R. China.
² Tianjin Key Laboratory of Early Draggability Evaluation of Innovative Drugs, Tianjin International Joint Academy of Biomedicine, Tianjin 300384, P.R. China.

Abstract

Adenoid cystic carcinoma of the lacrimal gland (LACC) is a major orbital malignancy. The recurrence rate and mortality rate are higher in LACC high-grade transformation (LACC-HGT) compared with in LACC. The present study aimed to identify the candidate microRNAs (miRNAs/miRs) and construct a competing endogenous RNA (ceRNA) regulatory network for LACC-HGT. A miRNA microarray on paraffin-embedded tissues was performed to identify the differentially expressed miRNAs (DEMs) of LACC-HGT. The overlap with the salivary adenoid cystic carcinoma miRNA/RNA sequencing dataset in the Gene Expression Omnibus was used to identify candidate miRNAs. In order to construct a ceRNA regulatory network of LACC-HGT, a microarray of mRNA and circRNA in primary cell lines was performed. The circRNAs and genes with high expression in LACC-HGT were predicted as targeting miRNAs, and the circRNA-miRNA-mRNA regulatory network was constructed. miR-140-3p was identified as part of the ceRNA network and as a candidate miRNA, therefore this was further analyzed using reverse transcription-quantitative (RT-q)PCR. Overall, the Agilent Human microarray analysis identified a total of 16 DEMs from the LACC-HGT paraffin-embedded tissues. A total of 653 DECs and 9,566 DEGs of LACC-HGT primary cell lines were screened via the microarray of mRNA and circRNA. The ceRNA regulatory network was constructed using the cross-binding of circRNA-miRNA, miRNA-mRNA and the downregulated miRNAs in LACC-HGT to clearly demonstrate the circRNA-miRNA-mRNA interaction relationship. RT-qPCR results confirmed that miR-140-3p was downregulated in LACC-HGT tissues and primary cell lines compared with LACC. Target genes CD200 and parathyroid hormone-related protein were significantly upregulated in LACC-HGT primary cell lines. miR-140-3p and its target genes may play an important role in LACC-HGT pathogenesis. In conclusion, the current bioinformatics study constructed a ceRNA network based on a microarray, which may help identify novel miRNA therapeutic targets for LACC-HGT.

Keywords: competing endogenous RNA; lacrimal gland adenoid cystic carcinoma with high-grade transformation; microarray.

Grants and funding

The present study was supported by a grant from The National Natural Science Foundation of China (grant no. 81570872) and The Tianjin Key Clinical Discipline Construction Project (grant nos. TJLCZDXKT006 and TJLCZDXKQ024), we acknowledge the support received from Tianjin Medical University Eye Institute.