Functional conservation of lncRNA<i>JPX</i>despite sequence and structural divergence

Karner, Heather; Webb, Chiu-Ho; Carmona, Sarah; Liu, Yu; Lin, Bryan; Erhard, Micaela; Chan, Dalen; Baldi, Pierre; Spitale, Robert C.; Sun, Sha

doi:10.1101/686113

Cited by 2 publications

References 87 publications

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Mechanistic diversification of XIST regulatory network in mammals

Rosspopoff¹,

Huret²,

Collier³

et al. 2019

Preprint

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X chromosome inactivation (XCI) is a developmental regulatory process that initiates with remarkable diversity in various mammalian species. Here we addressed the contribution of XCI 15 regulators, most of which are lncRNA genes characterized in the mouse, to this mechanistic diversity.By combining analysis of single-cell RNA-seq data from early human embryogenesis with various functional assays in naïve and primed pluripotent stem cells and in differentiated cells, we demonstrate that JPX is a major regulator of XIST expression in human and in mouse. However, the underlying mechanisms differ radically between species and require Jpx RNA in the mouse and the 20 act of transcription of JPX locus in the human. Moreover, biogenesis of XIST is affected at different regulatory steps between these species. This study illustrates how diversification of LRGs modes of action during evolution provide opportunities for innovations within constrained gene regulatory networks. 25 KEYWORDSX chromosome inactivation, XIST, JPX, lncRNA, pluripotency, single-cell RNA-seq, human embryogenesis, evolution, gene regulatory networks 30 Graphical abstract Xist RNA Ftx Jpx lncRNA Post-transcriptional effect JPX transcription XIST transcription FTX RNAPII recruitment Ht1 Mouse Human RNAPII CTCF mature RNA

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Mechanistic diversification of XIST regulatory network in mammals

Rosspopoff¹,

Huret²,

Collier³

et al. 2019

Preprint

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lncRNA JPX/miR-33a-5p/Twist1 axis regulates tumorigenesis and metastasis of lung cancer by activating Wnt/β-catenin signaling

et al. 2020

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Background MicroRNAs (miRNAs) and Twist1-induced epithelial-mesenchymal transition (EMT) in cancer cell dissemination are well established, but the involvement of long noncoding RNAs (lncRNAs) in Twist1-mediated signaling remains largely unknown. Methods RT-qPCR and western blotting were conducted to detect the expression levels of lncRNA JPX and Twist1 in lung cancer cell lines and tissues. The impact of JPX on Twist1 expression, cell growth, invasion, apoptosis, and in vivo tumor growth were investigated in lung cancer cells by western blotting, rescue experiments, colony formation assay, flow cytometry, and xenograft animal experiment. Results We observed that lncRNA JPX was upregulated in lung cancer metastatic tissues and was closely correlated with tumor size and an advanced stage. Functionally, JPX promoted lung cancer cell proliferation in vitro and facilitated lung tumor growth in vivo. Additionally, JPX upregulated Twist1 by competitively sponging miR-33a-5p and subsequently induced EMT and lung cancer cell invasion. Interestingly, JPX and Twist1 were coordinately upregulated in lung cancer tissues and cells. Mechanically, the JPX/miR-33a-5p/Twist1 axis participated in EMT progression by activating Wnt/β-catenin signaling. Conclusions These findings suggest that lncRNA JPX, a mediator of Twist1 signaling, could predispose lung cancer cells to metastasis and may serve as a potential target for targeted therapy.

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Functional conservation of lncRNAJPXdespite sequence and structural divergence

Cited by 2 publications

References 87 publications

Mechanistic diversification of XIST regulatory network in mammals

Mechanistic diversification of XIST regulatory network in mammals

lncRNA JPX/miR-33a-5p/Twist1 axis regulates tumorigenesis and metastasis of lung cancer by activating Wnt/β-catenin signaling

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