Integrated Analysis of Long Non-Coding RNA -mRNA Profile and Validation in Diabetic Cataract

ABSTRACT

Purpose

To illustrate the expression profile of lncRNAs and mRNAs in diabetic cataract (DC) and explore their potential role in the pathogenesis of DC.

Methods

LncRNA and mRNA microarray were conducted using the lens epithelium of DC patients (n = 3) and controls from eye bank (n = 3). Further, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were employed to unveil their underlying biological function and signaling pathway. The co-expression network was constructed to explore the relationship between lncRNAs and mRNAs. Then, lens epithelial cells (LECs) were cultured in vitro under high glucose (HG) and normal glucose (NG) groups to further verified the expression profiles of mRNAs. At last, quantitative RT-PCR (qRT-PCR) was performed to confirm the microarray results for the aberrantly expressed lncRNAs, and to unveil the expression prolife of mRNAs in LECs.

Results

Eight thousand three hundred and twenty-six lncRNAs and 3303 mRNAs were dysregulated in DC. GO analysis unveiled that the upregulated mRNAs, highest enrichment score of the GO term belonged to oxidation-reduction process, while the highest for downregulated mRNAs went to protein lipidation. In the CC category, the most significant terms for upregulated and downregulated mRNAs appeared in intracellular part and intrinsic component of membrane, respectively. As to MF category, the most significant term for upregulated mRNAs was protein binding, and for downregulated mRNAs was catecholamine binding. KEGG pathways analysis demonstrated that the major enrichment score of pathways in upregulated mRNAs included Glycolysis/Gluconeogenesis, lysosome, carbon metabolism and AGE-RAGE signaling pathway. For the downregulated mRNAs, the glycosphingolipid biosynthesis-lacto and neolacto series pathway was included. Three lncRNAs (LINC01508, MAFA-AS1, MIAT) and the Sirtuin 2 are positively related in the co-expression network.

Conclusions

This study provided an overview of the lncRNAs and mRNAs expression, and suggesting that several aberrantly expressed lncRNAs might participate in the pathogenesis of DC.

KEYWORDS:

• Long noncoding RNA
• mRNA
• diabetic cataract
• pathogenesis
• sirtuin 2

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Authors’ contribution

Xiaoyan Han and Zhixiang Hua collected the samples. Xiaoyan Han and Lei Cai performed the experiments, analyzed the data and wrote original draft article. Yumeng Shi performed the experiments needed for revised and drafted the revised article. Yi Lu designed the experiment. Jin Yang and Dan Li designed the experiments and revised the article. Xiaoyan Han and Lei Cai contribute equally to this work; Jin Yang and Dan Li also contribute equally to this work; All authors read and approved the final manuscript.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [Grant No. 82171039], General Fund of Shanghai Health Bureau [grant 201740033] and Xinjiang Production And Construction Corps Young and Middle-aged Science and Technology Innovation Leading Talents Program [grant 2020CB030].