Abstract

BackgroundTibetan chickens, a unique native breed in the Qinghai-Tibet Plateau of China, possess a suite of adaptive features that enable them to tolerate the high-altitude hypoxic environment. Increasing evidence suggests that long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) play roles in the hypoxic adaptation of high-altitude animals, although their exact involvement remains unclear.ResultsThis study aimed to elucidate the global landscape of mRNAs, lncRNAs, and miRNAs using transcriptome sequencing to construct a regulatory network of competing endogenous RNAs (ceRNAs) and thus provide insights into the hypoxic adaptation of Tibetan chicken embryos. In total, 354 differentially expressed genes (DE genes), 389 differentially expressed lncRNAs (DE lncRNAs), and 73 differentially expressed miRNAs (DE miRNAs) were identified between Tibetan chickens (TC) and control Chahua chickens (CH). GO and KEGG enrichment analysis revealed that several important DE miRNAs and their target DE lncRNAs and DE genes are involved in angiogenesis (including blood vessel development and blood circulation) and energy metabolism (including glucose, carbohydrate, and lipid metabolism). The ceRNA network was then constructed with the predicted DE gene-DE miRNA-DE lncRNA interactions, which further revealed the regulatory roles of these differentially expressed RNAs during hypoxic adaptation of Tibetan chickens.ConclusionsAnalysis of transcriptomic data revealed several key candidate ceRNAs that may play high-priority roles in the hypoxic adaptation of Tibetan chickens by regulating angiogenesis and energy metabolism. These results provide insights into the molecular mechanisms of hypoxic adaptation regulatory networks from the perspective of coding and non-coding RNAs.

Highlights

  • Tibetan chickens, a unique native breed in the Qinghai-Tibet Plateau of China, possess a suite of adaptive features that enable them to tolerate the high-altitude hypoxic environment

  • We identified 10 known mRNAs that were related to hypoxic adaptation and involved in angiogenesis and blood circulation (NGFR, ACTC1, CASQ2, ERBB4, KCNMB4, NCS1, and NTSR1) (Fig. 6a), as well as energy metabolism (SSTR5, NR1H4, and GBE) (Fig. 6b)

  • KCNMB4 has been reported to regulate blood pressure and was enriched in the Gene Ontology (GO) terms of regulation of vasoconstriction, ion transport, and vascular smooth muscle contraction pathway [41]. These findings indicate that Tibetan chickens can improve blood circulation and stimulate the activity of HIF-1 through upregulation of ACTC1 and NCS1, and Tibetan chickens promote vasodilation through downregulation of KCNMB4 in Chorioallantoic membrane (CAM) to adapt to hypoxic conditions

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Summary

Introduction

A unique native breed in the Qinghai-Tibet Plateau of China, possess a suite of adaptive features that enable them to tolerate the high-altitude hypoxic environment. MicroRNAs (miRNAs) are small non-coding RNA molecules that inhibit gene expression by binding to specific mRNAs. LncRNAs are another type of noncoding RNA, with a length of more than 200 nucleotides (nt), that regulate gene expression through a number of mechanisms, including epigenetic regulation (genetic imprinting and chromatin remodeling), transcriptional regulation (transcription interference), post-transcriptional regulation (splicing), and so on [1]. LncRNAs are another type of noncoding RNA, with a length of more than 200 nucleotides (nt), that regulate gene expression through a number of mechanisms, including epigenetic regulation (genetic imprinting and chromatin remodeling), transcriptional regulation (transcription interference), post-transcriptional regulation (splicing), and so on [1] Both of these non-coding RNAs play different roles in various aspects of cellular function, including the regulation of hypoxia-related genes. There have been various studies on genes involved in high-altitude adaptation in humans and animals, the regulatory mechanism of non-coding RNAs involved in hypoxic adaptation remains largely unknown

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