慢性镉暴露下食管鳞状细胞癌细胞的lncRNA-mRNA共表达网络分析

doi:10.3969/j.issn.1004-616x.2023.04.004

Abstract

Abstract: OBJECTIVE： To investigate involvement of the long non-coding RNA (lncRNA) and messenger RNA (mRNA) co-expression network in chronic low-dose cadmium exposure in esophageal squamous carcinoma (ESCC) cells，and to explore molecular mechanisms of hub lncRNAs and mRNAs in the cadmium-associated cancer progression and chemo-and radio-resistance. METHODS： EC109 cells were continually treated with 5 μmol/L cadmium chloride over 12 weeks to construct the chronic cadmium treated (CCT)-ESCC cell model，named as CCT-EC109. The whole-transcriptome sequencing was performed by the Illumina NovaSeq 6000 system，and then bioinformatics methods were applied to identify the differentially expressed (DE)- lncRNA and DE-mRNA expression profiles. Functions of target genes of DE-lncRNA were then predicted based on gene ontology (GO) and the Kyoto encyclopedia of genes and genomes (KEGG) forecast analysis. The lncRNA-mRNA co-expression network was conducted based on the Pearson correlation coefficient and the screened lncRNAs and mRNAs were verified using quantitative real-time polymerase chain reaction (qPCR). RESULTS： A total of 2 794 DE-lncRNAs and 4 267 DE-mRNAs were identified in the EC109 and CCT-EC109 cells. Intersection of the target genes of DE-lncRNA and DE-mRNAs yielded 1 546 cadmium-related mRNAs targeted by corresponding DE-lncRNA. GO analysis showed these genes were mainly enriched in metabolic process，membrane components and membrane closed cavity，and catalytic reaction，etc. For KEGG analysis，Hippo was shown to be the most significant enrichment pathway. Thirty-eight mRNAs were identified to be co-expressed with the top ten DE-lncRNAs. The results of qPCR assay indicated that both the key lncRNA NONHSAT097388.2 and its co-expressed mRNAs including EMP2，ECE1，ORAI1，and ZNF713，were significantly downregulated in the exposed cell line (all P<0.01)，while the expressions of PGF and MFAP5 were found to be upregulated (both of P<0.05). CONCLUSION： LncRNA-mRNA co-expression networks may play important roles in the mechanisms of progression and resistance in ESCC cells chronically exposed to cadmium. Meanwhile，these hub RNAs may serve as prognostic biomarkers or therapeutic targets for the ESCC patients with cadmium exposure.

Key words: cadmium, esophageal squamous carcinoma cell, long non-coding RNA, messenger RNA, co-expression network

CLC Number:

R735.1

PENG Lin, ZENG Mingqin, CHEN Jiongyu, ZHANG Xiarong, ZHU Rui, HUANG Yiteng. Integrative lncRNA-mRNA co-expression network analysis in the chronic cadmium-exposed esophageal squamous cell carcinoma cell[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(4): 266-272,278.

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Integrative lncRNA-mRNA co-expression network analysis in the chronic cadmium-exposed esophageal squamous cell carcinoma cell

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