Regulatory role of lncRNA MSTRG.11540.1 on the novel-m1192-3p/CYP2C70 axis in modulating albendazole resistance in Haemonchus contortus
Abstract Background To investigate the role of long non-coding RNAs (lncRNAs) in the regulation of albendazole resistance in Haemonchus contortus (H. contortus) through competing endogenous RNA (ceRNA) mechanisms, a ceRNA network analysis was performed based on RNA-seq data from albendazole-sensitiv...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-08-01
|
| Series: | BMC Veterinary Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12917-025-04966-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849735830430547968 |
|---|---|
| author | Xindi Chen Tengyu Wang Xu Yan Ya Su Wa Gao Chunxia Liu Huilin Kou Yu Yu Xianran Meng Wenlong Wang Wenrui Guo |
| author_facet | Xindi Chen Tengyu Wang Xu Yan Ya Su Wa Gao Chunxia Liu Huilin Kou Yu Yu Xianran Meng Wenlong Wang Wenrui Guo |
| author_sort | Xindi Chen |
| collection | DOAJ |
| description | Abstract Background To investigate the role of long non-coding RNAs (lncRNAs) in the regulation of albendazole resistance in Haemonchus contortus (H. contortus) through competing endogenous RNA (ceRNA) mechanisms, a ceRNA network analysis was performed based on RNA-seq data from albendazole-sensitive and albendazole-resistant strains. Starting with significantly upregulated lncRNAs and incorporating functional enrichment analysis of predicted target genes, a potential regulatory axis—MSTRG.11540.1/novel-m1192-3p/HCON_00073890 (CYP2C70)—was identified from the ceRNA network. Transcriptomic analysis revealed that MSTRG.11540.1 and CYP2C70 were significantly upregulated (fold changes of 1.20 and 4.01, respectively; P < 0.01), while novel-m1192-3p was significantly downregulated (fold change: 5.91; P < 0.05) in resistant strains. This study employed dual-luciferase reporter assays and RNA interference (RNAi) to validate the interactions and functional relevance of the candidate RNA molecules. Furthermore, an egg hatch assay (EHA) was conducted to assess the impact of the lncRNA-mediated ceRNA axis on albendazole resistance. The aim was to provide insights into the molecular mechanisms by which lncRNAs may regulate drug resistance in H. contortus. Results A dual-luciferase reporter plasmid containing the predicted binding sites was constructed to investigate the candidate ceRNA axis MSTRG.11540.1/novel-m1192-3p/CYP2C70. The interaction assay revealed that novel-m1192-3p binds to MSTRG.11540.1, but no direct binding was observed between novel-m1192-3p and its predicted target gene CYP2C70. However, overexpression of novel-m1192-3p downregulated the expression of both MSTRG.11540.1 (45.71% reduction compared to NC group, P > 0.05) and CYP2C70 (40.74% reduction versus NC group, P < 0.05). Subsequent RNAi experiments confirmed the existence of the MSTRG.11540.1/novel-m1192-3p/CYP2C70 regulatory axis. Moreover, EHA results showed that knockdown of MSTRG.11540.1 significantly decreased the LD50 value of albendazole (52.91 µg/mL to 32.02 µg/mL). Conclusions This study confirmed that the lncRNA-mediated ceRNA axis MSTRG.11540.1/novel-m1192-3p/CYP2C70 is involved in the regulation of albendazole resistance in H. contortus. These findings provide potential molecular targets for further elucidation of anthelmintic resistance mechanisms and the development of novel therapeutic strategies. |
| format | Article |
| id | doaj-art-590caeca99024142987e65722c17db8a |
| institution | DOAJ |
| issn | 1746-6148 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Veterinary Research |
| spelling | doaj-art-590caeca99024142987e65722c17db8a2025-08-20T03:07:27ZengBMCBMC Veterinary Research1746-61482025-08-0121111210.1186/s12917-025-04966-8Regulatory role of lncRNA MSTRG.11540.1 on the novel-m1192-3p/CYP2C70 axis in modulating albendazole resistance in Haemonchus contortusXindi Chen0Tengyu Wang1Xu Yan2Ya Su3Wa Gao4Chunxia Liu5Huilin Kou6Yu Yu7Xianran Meng8Wenlong Wang9Wenrui Guo10Key Laboratory of Animal Disease Clinical Diagnosis and Treatment Technology, College of Veterinary Medicine, Inner Mongolia Agricultural UniversityKey Laboratory of Animal Disease Clinical Diagnosis and Treatment Technology, College of Veterinary Medicine, Inner Mongolia Agricultural UniversityNational Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural UniversityDepartment of Husbandry and Veterinary, Ulanqab Vocational CollegeInner Mongolia Key Laboratory of Tick-Borne Zoonotic Infectious Disease, Department of Medicine, Hetao CollegeKey Laboratory of Animal Disease Clinical Diagnosis and Treatment Technology, College of Life Science, Inner Mongolia Agricultural UniversityKey Laboratory of Animal Disease Clinical Diagnosis and Treatment Technology, College of Veterinary Medicine, Inner Mongolia Agricultural UniversityKey Laboratory of Animal Disease Clinical Diagnosis and Treatment Technology, College of Veterinary Medicine, Inner Mongolia Agricultural UniversityKey Laboratory of Animal Disease Clinical Diagnosis and Treatment Technology, College of Veterinary Medicine, Inner Mongolia Agricultural UniversityKey Laboratory of Animal Disease Clinical Diagnosis and Treatment Technology, College of Veterinary Medicine, Inner Mongolia Agricultural UniversityKey Laboratory of Animal Disease Clinical Diagnosis and Treatment Technology, College of Veterinary Medicine, Inner Mongolia Agricultural UniversityAbstract Background To investigate the role of long non-coding RNAs (lncRNAs) in the regulation of albendazole resistance in Haemonchus contortus (H. contortus) through competing endogenous RNA (ceRNA) mechanisms, a ceRNA network analysis was performed based on RNA-seq data from albendazole-sensitive and albendazole-resistant strains. Starting with significantly upregulated lncRNAs and incorporating functional enrichment analysis of predicted target genes, a potential regulatory axis—MSTRG.11540.1/novel-m1192-3p/HCON_00073890 (CYP2C70)—was identified from the ceRNA network. Transcriptomic analysis revealed that MSTRG.11540.1 and CYP2C70 were significantly upregulated (fold changes of 1.20 and 4.01, respectively; P < 0.01), while novel-m1192-3p was significantly downregulated (fold change: 5.91; P < 0.05) in resistant strains. This study employed dual-luciferase reporter assays and RNA interference (RNAi) to validate the interactions and functional relevance of the candidate RNA molecules. Furthermore, an egg hatch assay (EHA) was conducted to assess the impact of the lncRNA-mediated ceRNA axis on albendazole resistance. The aim was to provide insights into the molecular mechanisms by which lncRNAs may regulate drug resistance in H. contortus. Results A dual-luciferase reporter plasmid containing the predicted binding sites was constructed to investigate the candidate ceRNA axis MSTRG.11540.1/novel-m1192-3p/CYP2C70. The interaction assay revealed that novel-m1192-3p binds to MSTRG.11540.1, but no direct binding was observed between novel-m1192-3p and its predicted target gene CYP2C70. However, overexpression of novel-m1192-3p downregulated the expression of both MSTRG.11540.1 (45.71% reduction compared to NC group, P > 0.05) and CYP2C70 (40.74% reduction versus NC group, P < 0.05). Subsequent RNAi experiments confirmed the existence of the MSTRG.11540.1/novel-m1192-3p/CYP2C70 regulatory axis. Moreover, EHA results showed that knockdown of MSTRG.11540.1 significantly decreased the LD50 value of albendazole (52.91 µg/mL to 32.02 µg/mL). Conclusions This study confirmed that the lncRNA-mediated ceRNA axis MSTRG.11540.1/novel-m1192-3p/CYP2C70 is involved in the regulation of albendazole resistance in H. contortus. These findings provide potential molecular targets for further elucidation of anthelmintic resistance mechanisms and the development of novel therapeutic strategies.https://doi.org/10.1186/s12917-025-04966-8Haemonchus contortusAlbendazoleDrug resistanceLncRNACeRNARNAi |
| spellingShingle | Xindi Chen Tengyu Wang Xu Yan Ya Su Wa Gao Chunxia Liu Huilin Kou Yu Yu Xianran Meng Wenlong Wang Wenrui Guo Regulatory role of lncRNA MSTRG.11540.1 on the novel-m1192-3p/CYP2C70 axis in modulating albendazole resistance in Haemonchus contortus BMC Veterinary Research Haemonchus contortus Albendazole Drug resistance LncRNA CeRNA RNAi |
| title | Regulatory role of lncRNA MSTRG.11540.1 on the novel-m1192-3p/CYP2C70 axis in modulating albendazole resistance in Haemonchus contortus |
| title_full | Regulatory role of lncRNA MSTRG.11540.1 on the novel-m1192-3p/CYP2C70 axis in modulating albendazole resistance in Haemonchus contortus |
| title_fullStr | Regulatory role of lncRNA MSTRG.11540.1 on the novel-m1192-3p/CYP2C70 axis in modulating albendazole resistance in Haemonchus contortus |
| title_full_unstemmed | Regulatory role of lncRNA MSTRG.11540.1 on the novel-m1192-3p/CYP2C70 axis in modulating albendazole resistance in Haemonchus contortus |
| title_short | Regulatory role of lncRNA MSTRG.11540.1 on the novel-m1192-3p/CYP2C70 axis in modulating albendazole resistance in Haemonchus contortus |
| title_sort | regulatory role of lncrna mstrg 11540 1 on the novel m1192 3p cyp2c70 axis in modulating albendazole resistance in haemonchus contortus |
| topic | Haemonchus contortus Albendazole Drug resistance LncRNA CeRNA RNAi |
| url | https://doi.org/10.1186/s12917-025-04966-8 |
| work_keys_str_mv | AT xindichen regulatoryroleoflncrnamstrg115401onthenovelm11923pcyp2c70axisinmodulatingalbendazoleresistanceinhaemonchuscontortus AT tengyuwang regulatoryroleoflncrnamstrg115401onthenovelm11923pcyp2c70axisinmodulatingalbendazoleresistanceinhaemonchuscontortus AT xuyan regulatoryroleoflncrnamstrg115401onthenovelm11923pcyp2c70axisinmodulatingalbendazoleresistanceinhaemonchuscontortus AT yasu regulatoryroleoflncrnamstrg115401onthenovelm11923pcyp2c70axisinmodulatingalbendazoleresistanceinhaemonchuscontortus AT wagao regulatoryroleoflncrnamstrg115401onthenovelm11923pcyp2c70axisinmodulatingalbendazoleresistanceinhaemonchuscontortus AT chunxialiu regulatoryroleoflncrnamstrg115401onthenovelm11923pcyp2c70axisinmodulatingalbendazoleresistanceinhaemonchuscontortus AT huilinkou regulatoryroleoflncrnamstrg115401onthenovelm11923pcyp2c70axisinmodulatingalbendazoleresistanceinhaemonchuscontortus AT yuyu regulatoryroleoflncrnamstrg115401onthenovelm11923pcyp2c70axisinmodulatingalbendazoleresistanceinhaemonchuscontortus AT xianranmeng regulatoryroleoflncrnamstrg115401onthenovelm11923pcyp2c70axisinmodulatingalbendazoleresistanceinhaemonchuscontortus AT wenlongwang regulatoryroleoflncrnamstrg115401onthenovelm11923pcyp2c70axisinmodulatingalbendazoleresistanceinhaemonchuscontortus AT wenruiguo regulatoryroleoflncrnamstrg115401onthenovelm11923pcyp2c70axisinmodulatingalbendazoleresistanceinhaemonchuscontortus |