Interactome analysis illustrates diverse gene regulatory processes associated with LIN28A in human iPS cell-derived neural progenitor cells

Yu, Nam-Kyung; McClatchy, Daniel B.; Diedrich, Jolene K.; Romero, Sarah; Choi, Ji Sun; Martínez‐Bartolomé, Salvador; Delahunty, Claire; Muotri, Alysson R.; Yates, John R.

doi:10.1016/j.isci.2021.103321

Cited by 4 publications

(2 citation statements)

References 105 publications

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“…Anti-Lin28a antibodies can detect multiple species of differing mobility across tissues and developmental stages, possibly contributed to by diverse post-translational modifications. 44 , 61 , 94 , 95 , 96 , 97 , 98 , 99 We knocked-in a myc epitope tag to the endogenous Lin28a locus to unambiguously identify Lin28a protein. Elevated levels of Lin28a protein were observed in the Fmr1 KO condition compared to Fmr1 WT siblings ( Figures 3 B and S3 B) by immunoprecipitation and blotting of embryonic forebrain (E15 - E16) lysates against the myc epitope tag.…”

Section: Resultsmentioning

confidence: 99%

Growth-suppressor microRNAs mediate synaptic overgrowth and behavioral deficits in Fragile X mental retardation protein deficiency

Subramanian,

Mills,

Paranjpe

et al. 2024

iScience

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Section: Resultsmentioning

confidence: 99%

Growth-suppressor microRNAs mediate synaptic overgrowth and behavioral deficits in Fragile X mental retardation protein deficiency

Subramanian,

Mills,

Paranjpe

et al. 2024

iScience

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“…2E, Supplementary Tables 1-2). By contrast, the RNA binding protein LIN28A, which was experimentally shown to interact with SMARCA4 and SMARCB1 41 , was upregulated only at the transcriptomic level in almost all SWI/SNF mutants (log2FC = 4.66 -8.38; Fig. 2D, Supplementary Tables 1-2).…”

Section: Loss Of Individual Swi/snf Subunits Distinctly Alters Gene A...mentioning

confidence: 96%

Integrated multiomic profiling reveals SWI/SNF subunit-specific pathway alterations and targetable vulnerabilities

Santamarina,

Astier,

Garrido

et al. 2024

Preprint

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SummaryMutations in subunits of the SWItch Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex occur in ≈20% of cancers and represent a highly unmet medical need. To identify novel therapeutic approaches, we systematically characterized transcriptomic and proteomic changes caused by the loss of SWI/SNF subunits or other epigenetic enzymes in isogenic cell lines, which we subsequently integrated with high-throughput drug screening and independent genetic screens of the DepMap project. Using an optimized bioinformatics pipeline for pathway enrichment, we identifiedMetabolism of proteinsas the most frequently dysregulated Reactome pathway category in SWI/SNF-defective cell lines. Drug screening and multiomic integration revealed multiple chemicals selectively cytotoxic for SWI/SNF-defective models, including CBP/EP300 or mitochondrial respiration inhibitors. A novel algorithm for the analysis of DepMap CRISPR screens independently identified synthetic lethality between SWI/SNF defects andEP300or mitochondrial respiration genes, which we further revalidated in disease-relevant models. These results unravel novel genetic dependencies for SWI/SNF-defective cancers.

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C/EBPβ-Lin28a positive feedback loop triggered by C/EBPβ hypomethylation enhances the proliferation and migration of vascular smooth muscle cells in restenosis

Zhou,

Jiang,

Guo

et al. 2024

Chinese Medical Journal

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Background: The main cause of restenosis after percutaneous transluminal angioplasty (PTA) is the excessive proliferation and migration of vascular smooth muscle cells (VSMCs). Lin28a has been reported to play critical regulatory roles in this process. However, whether CCAAT/enhancer-binding proteins β (C/EBPβ) binds to the Lin28a promoter and drives the progression of restenosis has not been clarified. Therefore, in the present study, we aim to clarify the role of C/EBPβ–Lin28a axis in restenosis. Methods: Restenosis and atherosclerosis rat models of type 2 diabetes (n = 20, for each group) were established by subjecting to PTA. Subsequently, the difference in DNA methylation status and expression of C/EBPβ between the two groups were assessed. EdU, Transwell, and rescue assays were performed to assess the effect of C/EBPβ on the proliferation and migration of VSMCs. DNA methylation status was further assessed using Methyltarget sequencing. The interaction between Lin28a and ten-eleven translocation 1 (TET1) was analysed using co-immunoprecipitation (Co-IP) assay. Student’s t-test and one-way analysis of variance were used for statistical analysis. Results: C/EBPβ expression was upregulated and accompanied by hypomethylation of its promoter in restenosis when compared with atherosclerosis. In vitro C/EBP β overexpression facilitated the proliferation and migration of VSMCs and was associated with increased Lin28a expression. Conversely, C/EBP β knockdown resulted in the opposite effects. Chromatin immunoprecipitation assays further demonstrated that C/EBPβ could directly bind to Lin28a promoter. Increased C/EBPβ expression and enhanced proliferation and migration of VSMCs were observed after decitabine treatment. Further, mechanical stretch promoted C/EBPβ and Lin28a expression accompanied by C/EBP β hypomethylation. Additionally, Lin28a overexpression reduced C/EBP β methylation via recruiting TET1 and enhanced C/EBPβ-mediated proliferation and migration of VSMCs. The opposite was noted in Lin28a knockdown cells. Conclusion: Our findings suggest that the C/EBPβ–Lin28a axis is a driver of restenosis progression, and presents a promising therapeutic target for restenosis.

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Interactome analysis illustrates diverse gene regulatory processes associated with LIN28A in human iPS cell-derived neural progenitor cells

Cited by 4 publications

References 105 publications

Growth-suppressor microRNAs mediate synaptic overgrowth and behavioral deficits in Fragile X mental retardation protein deficiency

Growth-suppressor microRNAs mediate synaptic overgrowth and behavioral deficits in Fragile X mental retardation protein deficiency

Integrated multiomic profiling reveals SWI/SNF subunit-specific pathway alterations and targetable vulnerabilities

C/EBPβ-Lin28a positive feedback loop triggered by C/EBPβ hypomethylation enhances the proliferation and migration of vascular smooth muscle cells in restenosis

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