Background Although several transcriptomic studies have explored the association between non-coding RNAs and Haemonchus contortus (H. contortus), the specific regulatory roles and mechanisms of long non-coding RNAs (lncRNAs) in the development of albendazole resistance remain insufficiently investigated. Objective The Illumina HiSeq™ 4000 sequencing platform was used to sequence the transcriptomes of albendazole-resistant H. contortus strains before (RA) and after (RB) administration. Methods For lncRNAs and messenger RNAs (mRNAs), association prediction of differentially expressed lncRNAs (DElncRNAs), differentially expressed mRNAs (DEmRNAs), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed. In parallel, an lncRNA/circRNA-miRNA-mRNA network was constructed and subjected to a functional enrichment analysis. The expression of lncRNAs and mRNAs was validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results In total, 1056 and 1072 novel lncRNAs were identified in the pre- and post-treatment groups, respectively. In albendazole-treated H. contortus samples, 15 lncRNAs and 149 mRNAs were dysregulated. The lncRNA MSTRG.1402.2, and the mRNA HCON_00154070 exhibited the most pronounced differences. GO enrichment analysis revealed that the mRNAs that exhibited aberrant expression following drug stimulation were involved in L-serine metabolic process, alpha-amino acid metabolic process, and oxidoreductase activity. KEGG analysis revealed that HCON_00130050 and HCON_00085890 were significantly enriched in the drug resistance ATP-binding cassette (ABC) transporter pathway. Furthermore, most of the target genes in the constructed MSTRG.3225.1/HCON_00036870, MSTRG.13862.3/HCON_00190400, and MSTRG.1643.2/miR-236-y/HCON_00110540 networks were enriched in metabolic and hormone regulatory pathways, including glutathione metabolism, insulin secretion, and endocrine and other factor-regulated calcium reabsorption. Moreover, qRT-PCR results demonstrated the accuracy of the transcriptome sequencing results. Conclusions After albendazole treatment, there were significantly differentially expressed lncRNAs and mRNAs in H. contortus, and some lncRNAs may be involved in the development of drug resistance by regulating metabolic pathways and ABC transporters.

Comparative analysis of lncRNA-mRNA networks in albendazole-resistant Haemonchus contortus

期刊论文
发表日期：

2025年11月6日

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Xindi Chen,
Tengyu Wang,
Chunxia Liu,
Weijie Wu,
Wenlong Wang

摘要

Background

Although several transcriptomic studies have explored the association between non-coding RNAs and Haemonchus contortus (H. contortus), the specific regulatory roles and mechanisms of long non-coding RNAs (lncRNAs) in the development of albendazole resistance remain insufficiently investigated.

Objective

The Illumina HiSeq™ 4000 sequencing platform was used to sequence the transcriptomes of albendazole-resistant H. contortus strains before (RA) and after (RB) administration.

Methods

For lncRNAs and messenger RNAs (mRNAs), association prediction of differentially expressed lncRNAs (DElncRNAs), differentially expressed mRNAs (DEmRNAs), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed. In parallel, an lncRNA/circRNA-miRNA-mRNA network was constructed and subjected to a functional enrichment analysis. The expression of lncRNAs and mRNAs was validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR).

Results

In total, 1056 and 1072 novel lncRNAs were identified in the pre- and post-treatment groups, respectively. In albendazole-treated H. contortus samples, 15 lncRNAs and 149 mRNAs were dysregulated. The lncRNA MSTRG.1402.2, and the mRNA HCON_00154070 exhibited the most pronounced differences. GO enrichment analysis revealed that the mRNAs that exhibited aberrant expression following drug stimulation were involved in L-serine metabolic process, alpha-amino acid metabolic process, and oxidoreductase activity. KEGG analysis revealed that HCON_00130050 and HCON_00085890 were significantly enriched in the drug resistance ATP-binding cassette (ABC) transporter pathway. Furthermore, most of the target genes in the constructed MSTRG.3225.1/HCON_00036870, MSTRG.13862.3/HCON_00190400, and MSTRG.1643.2/miR-236-y/HCON_00110540 networks were enriched in metabolic and hormone regulatory pathways, including glutathione metabolism, insulin secretion, and endocrine and other factor-regulated calcium reabsorption. Moreover, qRT-PCR results demonstrated the accuracy of the transcriptome sequencing results.

Conclusions

After albendazole treatment, there were significantly differentially expressed lncRNAs and mRNAs in H. contortus, and some lncRNAs may be involved in the development of drug resistance by regulating metabolic pathways and ABC transporters.