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GLIS3 expression in the thyroid gland in relation to TSH signaling and regulation of gene expression
In this study, we demonstrate that GLIS3 protein is first detectable at E15.5 of murine thyroid development, a time at which GLIS3 target genes, such as Slc5a5 (Nis), become expressed. This, together with observations showing that ubiquitous Glis3KO mice do not display major changes in prenatal thyroid gland morphology, indicated that CH in Glis3KO mice is due to dyshormonogenesis rather than thyroid dysgenesis. Analysis of GLIS3 in postnatal thyroid suggested a link between GLIS3 protein expression and blood TSH levels. This was supported by data showing that treatment with TSH, cAMP, or adenylyl cyclase activators or exp...
Source: Cellular and Molecular Life Sciences : CMLS - January 28, 2024 Category: Cytology Authors: Hong Soon Kang Sara A Grimm Xiao-Hui Liao Anton M Jetten Source Type: research

Functional role of Ash2l in oxLDL induced endothelial dysfunction and atherosclerosis
Cell Mol Life Sci. 2024 Jan 27;81(1):62. doi: 10.1007/s00018-024-05130-5.ABSTRACTEndothelial injury and dysfunction in the artery wall fuel the process of atherosclerosis. As a key epigenetic regulator, Ash2l (Absent, small, or homeotic-Like 2) is involved in regulating vascular injury and its complications. However, the role of Ash2l in atherosclerosis has not yet been fully elucidated. Here, we found increased Ash2l expression in high-cholesterol diet-fed ApoE-/- mice and oxidized LDL (oxLDL) treated endothelial cells (ECs). Furthermore, Ash2l promoted the scavenger receptors transcription by catalyzing histone H3 lysine...
Source: Cellular and Molecular Life Sciences : CMLS - January 27, 2024 Category: Cytology Authors: Zhenghua Su Jinghuan Wang Chenxi Xiao Wen Zhong Jiayao Liu Xinhua Liu Yi Zhun Zhu Source Type: research

Re-expression of epigenetically silenced PTPRR by histone acetylation sensitizes RAS-mutant lung adenocarcinoma to SHP2 inhibition
Cell Mol Life Sci. 2024 Jan 28;81(1):64. doi: 10.1007/s00018-023-05034-w.ABSTRACTSilenced protein tyrosine phosphatase receptor type R (PTPRR) participates in mitogen-activated protein kinase (MAPK) signaling cascades during the genesis and development of tumors. Rat sarcoma virus (Ras) genes are frequently mutated in lung adenocarcinoma, thereby resulting in hyperactivation of downstream MAPK signaling. However, the molecular mechanism manipulating the regulation and function of PTPRR in RAS-mutant lung adenocarcinoma is not known. Patient records collected from the Cancer Genome Atlas and Gene Expression Omnibus showed t...
Source: Cellular and Molecular Life Sciences : CMLS - January 27, 2024 Category: Cytology Authors: Tingting Du Xiaowen Hu Zhenyan Hou Weida Wang Shen You Mingjin Wang Ming Ji Nina Xue Xiaoguang Chen Source Type: research

Targeted mutagenesis in mice via an engineered AsCas12f1 system
Cell Mol Life Sci. 2024 Jan 28;81(1):63. doi: 10.1007/s00018-023-05100-3.ABSTRACTSpCas9 and AsCas12a are widely utilized as genome editing tools in human cells, but their applications are largely limited by their bulky size. Recently, AsCas12f1 protein, with a small size (422 amino acids), has been demonstrated to be capable of cleaving double-stranded DNA protospacer adjacent motif (PAM). However, low editing efficiency and large differences in activity against different genomic loci have been a limitation in its application. Here, we show that engineered AsCas12f1 sgRNA has significantly improved the editing efficiency i...
Source: Cellular and Molecular Life Sciences : CMLS - January 27, 2024 Category: Cytology Authors: Peng Fan Hejun Wang Feiyu Zhao Tao Zhang Jinze Li Xiaodi Sun Yongduo Yu Haoyang Xiong Liangxue Lai Tingting Sui Source Type: research

Hypoxia-driven deSUMOylation of EXOSC10 promotes adaptive changes in the transcriptome profile
Cell Mol Life Sci. 2024 Jan 27;81(1):58. doi: 10.1007/s00018-023-05035-9.ABSTRACTReduced oxygen availability (hypoxia) triggers adaptive cellular responses via hypoxia-inducible factor (HIF)-dependent transcriptional activation. Adaptation to hypoxia also involves transcription-independent processes like post-translational modifications; however, these mechanisms are poorly characterized. Investigating the involvement of protein SUMOylation in response to hypoxia, we discovered that hypoxia strongly decreases the SUMOylation of Exosome subunit 10 (EXOSC10), the catalytic subunit of the RNA exosome, in an HIF-independent ma...
Source: Cellular and Molecular Life Sciences : CMLS - January 26, 2024 Category: Cytology Authors: Chrysa Filippopoulou Chairini C Thom é Sofia Perdikari Evgenia Ntini George Simos Katherine E Bohnsack Georgia Chachami Source Type: research

Vascular injury activates the ELK1/SND1/SRF pathway to promote vascular smooth muscle cell proliferative phenotype and neointimal hyperplasia
CONCLUSIONS: The present study identifies ELK1/SND1/SRF as a novel pathway in promoting the proliferative VSMC phenotype and neointimal hyperplasia in vascular injury, predisposing the vessels to pathological remodeling. This provides a potential therapeutic target for vascular stenosis.PMID:38279051 | PMC:PMC10817852 | DOI:10.1007/s00018-023-05095-x (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - January 26, 2024 Category: Cytology Authors: Chao Su Mingxia Liu Xuyang Yao Wei Hao Jinzheng Ma Yuanyuan Ren Xingjie Gao Lingbiao Xin Lin Ge Ying Yu Minxin Wei Jie Yang Source Type: research

APC mutations disrupt β-catenin destruction complex condensates organized by Axin phase separation
Cell Mol Life Sci. 2024 Jan 27;81(1):57. doi: 10.1007/s00018-023-05068-0.ABSTRACTThe Wnt/β-catenin pathway is critical to maintaining cell fate decisions. Recent study showed that liquid-liquid-phase separation (LLPS) of Axin organized the β-catenin destruction complex condensates in a normal cellular state. Mutations inactivating the APC gene are found in approximately 80% of all human colorectal cancer (CRC). However, the molecular mechanism of the formation of β-catenin destruction complex condensates organized by Axin phase separation and how APC mutations impact the condensates are still unclear. Here, we report th...
Source: Cellular and Molecular Life Sciences : CMLS - January 26, 2024 Category: Cytology Authors: Dan Zhang Qi-Qi Ni Shu-Yang Wang Wen-Feng He Ze-Xuan Hong Hui-Ye Liu Xiao-Hong Chen Li-Jie Chen Fang-Yi Han Ling-Jie Zhang Xiao-Ming Li Yan-Qing Ding Hong-Li Jiao Ya-Ping Ye Source Type: research

α-Synuclein reduces acetylserotonin O-methyltransferase mediated melatonin biosynthesis by microtubule-associated protein 1 light chain 3 beta-related degradation pathway
Cell Mol Life Sci. 2024 Jan 27;81(1):61. doi: 10.1007/s00018-023-05053-7.ABSTRACTPrevious studies have demonstrated that α-synuclein (α-SYN) is closely associated with rapid eye movement sleep behavior disorder (RBD) related to several neurodegenerative disorders. However, the exact molecular mechanisms are still rarely investigated. In the present study, we found that in the α-SYNA53T induced RBD-like behavior mouse model, the melatonin level in the plasma and pineal gland were significantly decreased. To elucidate the underlying mechanism of α-SYN-induced melatonin reduction, we investigated the effect of α-SYN in m...
Source: Cellular and Molecular Life Sciences : CMLS - January 26, 2024 Category: Cytology Authors: Congcong Jia Lulu Tian Cheng Cheng Jun Zhang Murad Al-Nusaif Tianbai Li Huijia Yang Yushan Lin Song Li Weidong Le Source Type: research

Spatiotemporal modulation of nitric oxide and Notch signaling by hemodynamic-responsive Trpv4 is essential for ventricle regeneration
Cell Mol Life Sci. 2024 Jan 27;81(1):60. doi: 10.1007/s00018-023-05092-0.ABSTRACTZebrafish have a remarkable ability to regenerate injured hearts. Altered hemodynamic forces after larval ventricle ablation activate the endocardial Klf2a-Notch signaling cascade to direct zebrafish cardiac regeneration. However, how the heart perceives blood flow changes and initiates signaling pathways promoting regeneration is not fully understood. The present study demonstrated that the mechanosensitive channel Trpv4 sensed the altered hemodynamic forces in injured hearts and its expression was regulated by blood flow. In addition to medi...
Source: Cellular and Molecular Life Sciences : CMLS - January 26, 2024 Category: Cytology Authors: Chunxiao Yu Xueyu Li Jinmin Ma Shuzhang Liang Yan Zhao Qi Li Ruilin Zhang Source Type: research

Single  cell multi-omics of fibrotic kidney reveal epigenetic regulation of antioxidation and apoptosis within proximal tubule
CONCLUSIONS: In conclusion, as we know oxidation and apoptosis are traumatic factors during fibrosis, thus enhancing antioxidation and inhibiting the Nfix-Ifi27 pathway to inhibit apoptosis could be a potential treatment for kidney fibrosis.PMID:38270638 | PMC:PMC10811088 | DOI:10.1007/s00018-024-05118-1 (Source: Cellular and Molecular Life Sciences : CMLS)
Source: Cellular and Molecular Life Sciences : CMLS - January 25, 2024 Category: Cytology Authors: Zhejun Chen Liqing Ye Minyan Zhu Cong Xia Junfen Fan Hongbo Chen Zhijian Li Shan Mou Source Type: research

Tumor suppressor let-7 acts as a key regulator for pluripotency gene expression in Muse cells
Cell Mol Life Sci. 2024 Jan 23;81(1):54. doi: 10.1007/s00018-023-05089-9.ABSTRACTIn embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), the expression of an RNA-binding pluripotency-relevant protein, LIN28, and the absence of its antagonist, the tumor-suppressor microRNA (miRNA) let-7, play a key role in maintaining pluripotency. Muse cells are non-tumorigenic pluripotent-like stem cells residing in the bone marrow, peripheral blood, and organ connective tissues as pluripotent surface marker SSEA-3(+). They express pluripotency genes, differentiate into triploblastic-lineage cells, and self-renew at the...
Source: Cellular and Molecular Life Sciences : CMLS - January 23, 2024 Category: Cytology Authors: Gen Li Shohei Wakao Masaaki Kitada Mari Dezawa Source Type: research

Ribosomal protein L24 mediates mammalian microRNA processing in an evolutionarily conserved manner
Cell Mol Life Sci. 2024 Jan 23;81(1):55. doi: 10.1007/s00018-023-05088-w.ABSTRACTTo investigate the mechanism(s) underlying the expression of primate-specific microRNAs (miRs), we sought DNA regulatory elements and proteins mediating expression of the primate-specific hsa-miR-608 (miR-608), which is located in the SEMA4G gene and facilitates the cholinergic blockade of inflammation by targeting acetylcholinesterase mRNA. 'Humanized' mice carrying pre-miR-608 flanked by 250 bases of endogenous sequences inserted into the murine Sema4g gene successfully expressed miR-608. Moreover, by flanking miR-608 by shortened fragments ...
Source: Cellular and Molecular Life Sciences : CMLS - January 23, 2024 Category: Cytology Authors: Yonat Tzur Serafima Dubnov Nimrod Madrer Adi Bar Bettina Nadorp Nibha Mishra Paul Heppenstall Estelle R Bennett David S Greenberg Katarzyna Winek Hermona Soreq Source Type: research

Substrate promiscuity of Dicer toward precursors of the let-7 family and their 3'-end modifications
In this study, we systematically investigated the impact of sequence and structural features of all human let-7 pre-miRNAs, including their 3'-end modifications, on Dicer binding and processing. Through the combination of SHAPE structural probing, in vitro binding and kinetic studies using purified human Dicer, we show that despite structural discrepancies among pre-let-7 RNAs, Dicer exhibits remarkable promiscuity in binding and cleaving these substrates. Moreover, the 1- or 2-nt 3'-overhang, 3'-mono-uridylation, and 3'-oligo-uridylation of pre-let-7 substrates appear to have little effect on Dicer binding and cleavage ra...
Source: Cellular and Molecular Life Sciences : CMLS - January 23, 2024 Category: Cytology Authors: Gunjan Dadhwal Hebatallah Samy Jonathan Bouvette Fatima El-Azzouzi Pierre Dagenais Pascale Legault Source Type: research

FOXA2-initiated transcriptional activation of INHBA induced by methylmalonic acid promotes pancreatic neuroendocrine neoplasm progression
In this study, we first identified methylmalonic acid (MMA) as an oncometabolite for PanNEN progression, based on serum metabolomics of metastatic PanNEN compared with non-metastatic PanNEN patients. One of the key findings was the potentially novel mechanism of epithelial-mesenchymal transition (EMT) triggered by MMA. Inhibin βA (INHBA) was characterized as a key regulator of MMA-induced PanNEN progression according to transcriptomic analysis, which has been validated in vitro and in vivo. Mechanistically, INHBA was activated by FOXA2, a neuroendocrine (NE) specific transcription factor, which was initiated during MMA-in...
Source: Cellular and Molecular Life Sciences : CMLS - January 22, 2024 Category: Cytology Authors: Chunhua Hu Mujie Ye Jianan Bai Pengfei Liu Feiyu Lu Jinhao Chen Yanling Xu Lijun Yan Ping Yu Zequan Xiao Danyang Gu Lin Xu Ye Tian Qiyun Tang Source Type: research

Combination of blockade of endothelin signalling and compensation of IGF1 expression protects the retina from degeneration
Cell Mol Life Sci. 2024 Jan 22;81(1):51. doi: 10.1007/s00018-023-05087-x.ABSTRACTRetinitis pigmentosa (RP) and macular dystrophy (MD) cause severe retinal dysfunction, affecting 1 in 4000 people worldwide. This disease is currently assumed to be intractable, because effective therapeutic methods have not been established, regardless of genetic or sporadic traits. Here, we examined a RP mouse model in which the Prominin-1 (Prom1) gene was deficient and investigated the molecular events occurring at the outset of retinal dysfunction. We extracted the Prom1-deficient retina subjected to light exposure for a short time, conduc...
Source: Cellular and Molecular Life Sciences : CMLS - January 22, 2024 Category: Cytology Authors: Naoya Shigesada Naoya Shikada Manabu Shirai Michinori Toriyama Fumiaki Higashijima Kazuhiro Kimura Toru Kondo Yasumasa Bessho Takuma Shinozuka Noriaki Sasai Source Type: research