Genomics · 2026
Mechanistic insights into sheep pulmonary adenomatosis based on whole transcriptome sequencing.
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Zhu Lina, Li Qiao, Xiao Kaiyan, Shi Shujun, Chen Zhenghan, Wang Yumei, Zhang Rui, An Xuejiao, Yue Yaojing
Аннотация
OBJECTIVE: Sheep pulmonary adenocarcinoma (SPA), a chronic contagious lung neoplasm induced by jaagsiekte sheep retrovirus (JSRV), represents a unique animal model for studying virus-driven lung carcinogenesis. This study aimed to systematically dissect host transcriptional reprogramming in naturally infected lung tissues using whole-transcriptome sequencing and to identify core regulatory factors associated with SPA pathogenesis.
METHODS: Lung tumor tissues from naturally SPA-infected sheep and matched healthy lung tissues were collected as experimental samples. High-throughput whole-transcriptome sequencing was performed to profile coding and non-coding RNA expression. Differentially expressed mRNAs (DE-mRNAs), long non-coding RNAs (DE-lncRNAs), microRNAs (DE-miRNAs), and circular RNAs (DE-circRNAs) were identified through bioinformatic analyses. Functional enrichment analyses (Gene Ontology, GO) and Kyoto Encyclopedia of Genes and Genomes,KEGG) were conducted to elucidate the biological roles of these differentially expressed molecules. An integrative multi-omics approach was employed to construct a host endogenous competing endogenous RNA (ceRNA) regulatory network. Key differentially expressed molecules were further validated by RT-qPCR.
RESULTS: A total of 2067 DE-mRNAs, 72 DE-lncRNAs, 210 DE-miRNAs, and 477 DE-circRNAs were identified. Functional enrichment analyses revealed significant involvement of these molecules in key oncogenic signaling pathways, including MAPK, PI3K-Akt, mTOR, and Hippo. Integrative analysis enabled the construction of an SPA-specific ceRNA network, highlighting several critical regulatory axes: Novel_circ_008415-oar-miR-16b-ALDH1A2, MSTRG.36927.2-oar-miR-16b-CD22, and MSTRG.36932.1-oar-miR-16b-BCL2/CCND1. RT-qPCR validation confirmed that the expression trends of these key molecules were highly consistent with the sequencing data.
CONCLUSION: This study provides a comprehensive whole-transcriptome landscape of lung tissues from sheep naturally infected with SPA, uncovering the potential roles of non-coding RNAs-mediated via ceRNA mechanisms-in regulating tumor cell apoptosis, immune evasion, and malignant proliferation. Our findings offer novel molecular insights into JSRV-induced oncogenesis, identify candidate biomarkers for early diagnosis, and lay a theoretical foundation for the development of targeted therapeutic strategies against SPA.
METHODS: Lung tumor tissues from naturally SPA-infected sheep and matched healthy lung tissues were collected as experimental samples. High-throughput whole-transcriptome sequencing was performed to profile coding and non-coding RNA expression. Differentially expressed mRNAs (DE-mRNAs), long non-coding RNAs (DE-lncRNAs), microRNAs (DE-miRNAs), and circular RNAs (DE-circRNAs) were identified through bioinformatic analyses. Functional enrichment analyses (Gene Ontology, GO) and Kyoto Encyclopedia of Genes and Genomes,KEGG) were conducted to elucidate the biological roles of these differentially expressed molecules. An integrative multi-omics approach was employed to construct a host endogenous competing endogenous RNA (ceRNA) regulatory network. Key differentially expressed molecules were further validated by RT-qPCR.
RESULTS: A total of 2067 DE-mRNAs, 72 DE-lncRNAs, 210 DE-miRNAs, and 477 DE-circRNAs were identified. Functional enrichment analyses revealed significant involvement of these molecules in key oncogenic signaling pathways, including MAPK, PI3K-Akt, mTOR, and Hippo. Integrative analysis enabled the construction of an SPA-specific ceRNA network, highlighting several critical regulatory axes: Novel_circ_008415-oar-miR-16b-ALDH1A2, MSTRG.36927.2-oar-miR-16b-CD22, and MSTRG.36932.1-oar-miR-16b-BCL2/CCND1. RT-qPCR validation confirmed that the expression trends of these key molecules were highly consistent with the sequencing data.
CONCLUSION: This study provides a comprehensive whole-transcriptome landscape of lung tissues from sheep naturally infected with SPA, uncovering the potential roles of non-coding RNAs-mediated via ceRNA mechanisms-in regulating tumor cell apoptosis, immune evasion, and malignant proliferation. Our findings offer novel molecular insights into JSRV-induced oncogenesis, identify candidate biomarkers for early diagnosis, and lay a theoretical foundation for the development of targeted therapeutic strategies against SPA.