PAX9 regulates squamous cell differentiation and carcinogenesis in the oro‐oesophageal epithelium

Xiong, Zhaohui; Ren, Shuang; Chen, Hao; Liu, Yao; Huang, Caizhi; Zhang, Yawan Lyvia; Odera, Joab Otieno; Chen, Tong; Kist, Ralf; Peters, Heiko; Garman, Katherine S.; Sun, Zheng; Chen, Xiaoxin

doi:10.1002/path.4998

Cited by 34 publications

(39 citation statements)

References 36 publications

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“…We found four genes with pecoran-specific CNEs within their immediate upstream/downstream 10-kbp regions (SIM2, PAX9, KCNK5, and DENND2C) (table S36), of which PAX9 and SIM2 are important transcriptional factors. PAX9 regulates squamous cell differentiation in the esophageal epithelium (82). A CNE with two pecoran-specific mutations was found at the 5′ upstream of PAX9 in pecorans, which might play a role in regulating PAX9 expression in the omasum.…”

Section: Genomic Variations Related To Ruminant Morphological Charactmentioning

confidence: 95%

Large-scale ruminant genome sequencing provides insights into their evolution and distinct traits

Chen¹,

Qiu²,

Jiang³

et al. 2019

Science

334

307

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The ruminants are one of the most successful mammalian lineages, exhibiting morphological and habitat diversity and containing several key livestock species. To better understand their evolution, we generated and analyzed de novo assembled genomes of 44 ruminant species, representing all six Ruminantia families. We used these genomes to create a time-calibrated phylogeny to resolve topological controversies, overcoming the challenges of incomplete lineage sorting. Population dynamic analyses show that population declines commenced between 100,000 and 50,000 years ago, which is concomitant with expansion in human populations. We also reveal genes and regulatory elements that possibly contribute to the evolution of the digestive system, cranial appendages, immune system, metabolism, body size, cursorial locomotion, and dentition of the ruminants.

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Section: Genomic Variations Related To Ruminant Morphological Charactmentioning

confidence: 95%

Large-scale ruminant genome sequencing provides insights into their evolution and distinct traits

Chen¹,

Qiu²,

Jiang³

et al. 2019

Science

334

307

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“…the abomasum of the ruminants, the third-chamber stomachs of camels and cetaceans). Notably, PAX9 23 , a known key transcription factor during esophagus differentiation, is highly expressed in all three FC stomachs and may play a role in the origin of the FC stomachs from their anatomic origin ( Supplementary Table 5 ). Our results therefore indicate that the FC stomachs in Cetartiodactyla share a common developmental origin from the esophagus, and that changes in epidermis development may be an ancestral feature in this proto-rumen.…”

Section: Resultsmentioning

confidence: 99%

Tracing the origin of a new organ by inferring the genetic basis of rumen evolution

Pan

Wang

et al. 2020

Preprint

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36The rumen is the hallmark organ of ruminants and hosts a diverse ecosystem of 37 microorganisms that facilitates efficient digestion of plant fibers. We used 897 38 transcriptomes from three Cetartiodactyla lineages: ruminants, camels and cetaceans, 39 as well as data from ruminant comparative genomics and functional assays to explore 40 the genetic basis of rumen origin and evolution. Comparative analyses reveal that the 41 rumen and the first-chamber stomachs of camels and cetaceans shared a common 42 tissue origin from the esophagus. The rumen recruited genes from other tissues/organs 43 and up-regulated many esophagus genes to aquire functional innovations involving 44 epithelium absorption, improvement of the ketone body metabolism and regulation of 45 microbial community. These innovations involve such genetic changes as 46 ruminant-specific conserved elements, newly evolved genes and positively selected 47 genes. Our in vitro experiements validate the functions of one enhancer, one 48 positively selected gene and two newly evolved antibacterial genes. Our study 49 provides novel insights into the origin and evolution of a complex organ. 50 3Evolutionary biology has a long history of trying to understand how complex organs 51 evolve 1 . The origin of some notable organs has been central to animal evolution, e.g. 52 the eyes of animals 2,3 , electric organs of fishes 4 , mammalian placenta 5,6 and ruminant 53 headgear 7 . Another remarkable organ innovation found in mammals are the 54 multi-chambered stomachs found in the Cetartiodactyla lineages, including Tylopoda 55 (e.g. camels), Tayassuidae (e.g. peccaries), Hippopotamidae (e.g. hippos), Cetacea 56 (e.g. whales) and Ruminantia (Fig. 1). Among these, ruminants have the most complex 57 digestive system in herbivores, allowing efficient uptake of nutrients from plant 58 material by providing a microbial fermentation ecosystem in the highly specialized 59 rumen 8 . Camels (Tylopoda) have three-chambered stomachs and are also sometimes 60 called "pseudo-ruminants" due to their similar ruminating behavior and microbial 61 fermentation taking place in their first-chamber (FC) stomach 9 . The whales (Cetacea) 62 form the sister group of the Ruminantia 10 , however the FC of their four-chambered 63 stomach is mainly used as a temporary storage chamber for ingested food and for 64 mechanical grinding of food items 11 . With the rumen, ruminants obtained a unique 65 evolutionary advantage through superior utilization of short chain fatty acids (SCFAs) 66 from microbial fermentation, which significantly promoted the expansion and 67 diversification of ruminant taxa 12 . The evolutionary innovation of the rumen is 68 therefore interesting not only in its functional complexity and uniqueness, but also 69 because it has greatly benefited humans by providing high-quality nutrition in the shape 70 of highly productive ruminant livestock species 13,14 . 71The anatomical predecessor from which the rumen evolved has been proposed to 72 4 be the esophagus 15 , yet the...

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“…LncRNA DIO3OS has been emphasized as a novel promising biomarker for the diagnosis of inflammatory bowel disease [16]. Interestingly, PAX9 has been established to modulate the differentiation of squamous cells and carcinogenesis in orooesophageal epithelium [28]. Additionally, PAX9 has been highlighted as a key player in the differentiation process of esophageal keratinocytes and internal stratified squamous epithelium [19].…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA DIO3OS Binds to microRNA-130b to Restore Radiosensitivity in Esophageal Squamous Cell Carcinoma by Upregulating PAX9

et al. 2019

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Background: Esophageal squamous cell carcinoma (ESCC) ranks as one of the most fatal cancers worldwide for its aggression and unsatisfactory survival rate. The long non-coding RNA (lncRNA)-microRNA (miRNA)-mRNA axis has been highlighted as a potency biomarker for enhancing the radiosensitivity of ESCC. Hence, we investigated the functional mechanism of the DIO3OS/miR-130b/paired box 9 (PAX9) axis in the radioresistance of ESCC cells. Methods: In cell experiments, we altered the miR-130b expression in ESCC cells using mimics or inhibitors to examine its effects on ESCC cell activities in response to 4 Gy irradiation, as well as the involvement of DIO3OS and PAX9. Tumor xenograft experiments were then conducted to observe the effect of miR-130b, DIO3OS and PAX9 on radiosensitivity of ESCC ells in vivo. Results: miR-130b was found to be highly-expressed in the ESCC. Downregulated miR-130b inhibited proliferation, invasion and resistance to apoptosis in ESCC cells. DIO3OS and PAX9 were reduced in ESCC. A notable finding revealed that miR-130b could bind to DIO3OS and PAX9 respectively. DIO3OS could upregulate PAX9 by binding to miR-130b, which ultimately promoted the radiosensitivity of ESCC in vitro and in vivo. Conclusion: Taken together, DIO3OS upregulates the expression of PAX9 by binding to miR-130b, ultimately promoting the radiosensitivity of ESCC.

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PAX9 regulates squamous cell differentiation and carcinogenesis in the oro‐oesophageal epithelium

Cited by 34 publications

References 36 publications

Large-scale ruminant genome sequencing provides insights into their evolution and distinct traits

Large-scale ruminant genome sequencing provides insights into their evolution and distinct traits

Tracing the origin of a new organ by inferring the genetic basis of rumen evolution

Long Non-Coding RNA DIO3OS Binds to microRNA-130b to Restore Radiosensitivity in Esophageal Squamous Cell Carcinoma by Upregulating PAX9

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