Deregulated lncRNA expression profile in the mouse lung adenocarcinomas with KRAS‐G12D mutation and P53 knockout

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by mutations in the GBA1 gene, which produces the glucocerebrosidase (GCase) protein. There are more than 500 mutations reported in GBA1, among which L444P (p.Leu444Pro) and F213I (p.Phe213Ile) are the most common in the Chinese population, while the function of F213I mutation remains elusive. This study aims to establish the GD mouse model of partially humanized Gba1 gene with F213I mutation. In vitro GCase activity assays showed that the product of partially humanized Gba1 gene, in which the mouse exons 5-7 were replace by the corresponding human exons, displayed similar activity with the wild-type mouse Gba1, while the F213I mutation in the humanized Gba1 led to significant decrease in enzyme activity. ES cell targeting was used to establish the mice expressing the partially humanized Gba1-F213I. Gba1F213I/+ mice did not show obviously abnormal phenotypes, but homozygous Gba1F213I/F213I mice died within 24 h after birth, whose epidermal stratum corneum were abnormal from the wild-type. The GCase activity in Gba1F213I/F213I mice greatly decreased. In conclusion, our results showed that the partially humanized GD mouse model with the F213I mutation was developed and homozygous F213I mutation is lethal for newborn mice.

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“…The primers are listed in Supplementary Table S1 . PCR was performed as reported by Zhang et al ( Zhang et al, 2019 ).…”

Section: Methodsmentioning

confidence: 99%

Establishment and Phenotypic Analysis of the Novel Gaucher Disease Mouse Model With the Partially Humanized Gba1 Gene and F213I Mutation

et al. 2022

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“…The primers are listed in Supplementary Table S3 . PCR was performed as reported by Zhang et al (2019) .…”

Section: Methodsmentioning

confidence: 99%

“…Feature Extraction Software v10.7 was used for data extraction from raw microarray image files. Quantile normalization and subsequent data processing were performed using the GeneSpring GX V13.0 software package (Agilent Technologies) ( Zhang et al, 2019 ).…”

Section: Methodsmentioning

confidence: 99%

Ablation of Zfhx4 results in early postnatal lethality by disrupting the respiratory center in mice

Zhang

et al. 2021

Journal of Molecular Cell Biology

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Breathing is an integrated motor behavior that is driven and controlled by a network of brainstem neurons. Zfhx4 is a zinc finger transcription factor and our results showed that it was specifically expressed in several regions of the mouse brainstem. Mice lacking Zfhx4 died shortly after birth from an apparent inability to initiate respiration. We also found that the electrical rhythm of brainstem‒spinal cord preparations was significantly depressed in Zfhx4-null mice compared to wild-type mice. Immunofluorescence staining revealed that Zfhx4 was co-expressed with Phox2b and Math1 in the brainstem and that Zfhx4 ablation greatly decreased the expression of these proteins, especially in the retrotrapezoid nucleus (RTN). Combined ChIP‒seq and mRNA expression microarray analysis identified Phox2b as the direct downstream target gene of Zfhx4, and this finding was validated by ChIP‒qPCR. Previous studies have reported that both Phox2b and Math1 play key roles in the development of the respiratory center, and Phox2b and Math1 knockout mice are neonatal lethal due to severe central apnea. On top of this, our study revealed that Zfhx4 is a critical regulator of Phox2b expression and essential for perinatal breathing.

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“…Intriguingly, p53 negatively regulated NONMMUT015812 expression. 95 PVT1b is a stress-specific PVT1 isoform activated by p53; activated PVT1b promoted transcriptional inhibition of Myc and inhibited cellular proliferation in LAD cell lines. 96 Furthermore, PVT1b loss enhanced tumor growth that indicated a potential to control lung cancer development by regulating PVT1b activity.…”

Section: Lncrnas Regulate Lung Cancer Metastasis By Regulating Signal...mentioning

confidence: 98%

Revisiting Lung Cancer Metastasis: Insight From the Functions of Long Non-coding RNAs

Huang

Zhu

Liang

et al. 2021

Technol Cancer Res Treat

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Globally, lung cancer is the most common cause of cancer-related deaths. After diagnosis at all stages, <7% of patients survive for 10 years. Thus, diagnosis at later stages and the lack of effective and personalized drugs reflect a significant need to better understand the mechanisms underpinning lung cancer progression. Metastasis should be responsible for the high lethality and recurrence rates seen in lung cancer. Metastasis depends on multiple crucial steps, including epithelial–mesenchymal transition, vascular remodeling, and colonization. Therefore, in-depth investigations of metastatic molecular mechanisms can provide valuable insights for lung cancer treatment. Recently, long noncoding RNAs (lncRNAs) have attracted considerable attention owing to their complex roles in cancer progression. In lung cancer, multiple lncRNAs have been reported to regulate metastasis. In this review, we highlight the major molecular mechanisms underlying lncRNA-mediated regulation of lung cancer metastasis, including (1) lncRNAs acting as competing endogenous RNAs, (2) lncRNAs regulating the transduction of several signal pathways, and (3) lncRNA coordination with enhancer of zeste homolog 2. Thus, lncRNAs appear to execute their functions on lung cancer metastasis by regulating angiogenesis, autophagy, aerobic glycolysis, and immune escape. However, more comprehensive studies are required to characterize these lncRNA regulatory networks in lung cancer metastasis, which can provide promising and innovative novel therapeutic strategies to combat this disease.

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Deregulated lncRNA expression profile in the mouse lung adenocarcinomas with KRAS‐G12D mutation and P53 knockout

Cited by 6 publications

References 29 publications

Establishment and Phenotypic Analysis of the Novel Gaucher Disease Mouse Model With the Partially Humanized Gba1 Gene and F213I Mutation

Establishment and Phenotypic Analysis of the Novel Gaucher Disease Mouse Model With the Partially Humanized Gba1 Gene and F213I Mutation

Ablation of Zfhx4 results in early postnatal lethality by disrupting the respiratory center in mice

Revisiting Lung Cancer Metastasis: Insight From the Functions of Long Non-coding RNAs

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