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CTNNB1
JOURNAL OF THE WORLD AQUACULTURE SOCIETY · 2024 · IF 2.3

Identification of CTNNB1 in the lined seahorse, Hippocampus erectus, and its function in innate immunity and cell proliferation

Lele Zhang,Fang Wang,Chunhui Lv,Lanliang Yu,Xiaojing Ci,Ning Zhang,Longwu Jia,Yuanyuan Xue,Xu Zhang,Xiaolei Su,Kai Wang

β-Catenin ( CTNNB ) is a core downstream mediator in the Wnt/β-catenin signaling pathway, which plays a role in immune regulation and cell differentiation. In the present study, two CTNNB genes were identified by genomic analysis of Hippocampus erectus and named He-CTNNB1 and He-CTNNB2 . He-CTNNB1 was more conserved than He-CTNNB2 . The full length of He-CTNNB1 was 2369 bp, including an open reading frame of 2275 bp that encoded 737 amino acids containing 12 armadillo repeats. Phylogenetic analysis revealed that He-CTNNB1 clusters had homologs in other bony fishes. Tissue distribution analysis showed the highest mRNA expression of He-CTNNB1 in the ovary, liver, and kidney of the lined seahorse under normal physiological conditions. The transcription level of He-CTNNB1 was significantly increased in the liver and kidney in response to LPS, poly I:C, and Edwardsiella tarda challenge ( p < 0.05). In vitro overexpression of He-CTNNB1 significantly upregulated the expression of key genes of the canonical Wnt/β-catenin signaling pathway, such as axin2 , cMyc , and cyclinD ( p < 0.05), which increased cell proliferation during the wound-healing process. Taken together, our results suggest that He-CTNNB1 is essential for cell proliferation and the innate immune response in H. erectus .

CAS / MDL: 9005-64-5
研究领域: 分子生物学 · 免疫学 · 鱼类生理学
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Cell Death & Disease · 2023 ·Vol. 14 ·期 2 ·1-14 · IF 9

RBM3 suppresses stemness remodeling of prostate cancer in bone microenvironment by modulating N6-methyladenosine on CTNNB1 mRNA

Zhang Shouyi,Lv Chengcheng,Niu Yichen,Li Changqi,Li Xiuming,Shang Yu,Zhang Yunchao,Zhang Yue,Zhang Yong,Zeng Yu

Bone metastasis is the most happened metastatic event in prostate cancer (PCa) and needs a large effort in treatment. When PCa metastasizes to the bone, the new microenvironment can induce the epigenome reprogramming and stemness remodeling of cancer cells, thereby increasing the adaptability of cancer cells to the bone microenvironment, and this even leads to the occurrence of secondary tumor metastasis. Our group has previously found that RNA binding motif 3 (RBM3) affects the stem cell-like properties of PCa by interfering with alternative splicing of CD44. However, whether RBM3, as a stress-response protein, can resist microenvironmental remodeling of PCa particularly in bone metastasis remains unknown. By co-culturing PCa cells with osteoblasts to mimic PCa bone metastases, we found that RBM3 upregulates the N6-methyladenosine (m 6 A) methylation on the mRNA of catenin beta 1 (CTNNB1) in a manner dependent on methyltransferase 3 (METTL3), an N6-adenosine-methyltransferase complex catalytic subunit. Consequently, this modification results in a decreased stability of CTNNB1 mRNA and a followed inactivation of Wnt signaling, which ultimately inhibits the stemness remodeling of PCa cells by osteoblasts. Thus, the present study may extend our understanding of the inhibitory role of RBM3 on particularly bone metastasis of PCa.

CAS / MDL: 50-76-0
研究领域: 肿瘤学 · 分子生物学 · 癌症生物学
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CELLULAR SIGNALLING · 2024 · IF 4.4

Decreased expression of KLF6 in ectopic endometrial stromal cells contributes to endometriosis progression by targeting CTNNB1

Jingwen Shi,Wenda Jing,Yueyun He,Ying Huang

Despite decades of research, endometriosis remains a mysterious gynecological disease with unknown etiology and pathogenesis. Krüppel-like Factor 6 (KLF6), a transcription factor, has a wide expression profile and regulates a variety of biological processes. Here, we investigated the expression and function of KLF6 and its possible regulatory mechanisms in endometriosis. To determine the function of KLF6, knockdown and overexpression experiments were performed in eutopic endometrial stromal cells (EU-ESCs) and ectopic endometrial stromal cells (EC-ESCs), respectively. Cell viability, apoptosis, migration, invasion, and angiogenesis assays were conducted in ESCs. ChIP-sequencing and mRNA-sequencing were performed to investigate the functional mechanism of KLF6 in regulating ESCs. We found that KLF6 was highly expressed in eutopic endometrium of endometriosis patients, compared with ectopic endometrium. Similarly, the same was true in EU-ESCs, which was compared with EC-ESCs. Overexpression of KLF6 significantly suppressed EC-ESC proliferation, migration and invasion and induced cell apoptosis, while knockdown of KLF6 resulted in the opposite effects on EU-ESCs. Overexpression of KLF6 significantly inhibited EC-ESC angiogenesis. Mechanistically, the results of ChIP sequencing and mRNA sequencing revealed that CTNNB1 may be a transcriptional target regulated by KLF6. Reintroduction of KLF6 reversed the effects of KLF6 knockdown on EU-ESCs. KLF6 inhibited the proliferation, migration and angiogenesis of EC-ESCs by inhibiting the expression of CTNNB1. Our findings provided a new perspective on the role of KLF6 in endometriosis progression and inspire potential targeted therapeutic strategies.

CAS / MDL: 30525-89-4 28718-90-3
研究领域: 妇科学 · 分子生物学 · 转录因子 · 疾病发病机制
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SENSORS AND ACTUATORS B-CHEMICAL · 2023 · IF 8.4

DNAzyme mediated catalytic hairpin self-assembly strategy enables the sensitive and facile investigation of N6-methyladenine

Xinghui Zhou,Chengpeng Li,Wanxue Wang,Feng Zhang,Yi Zhou,Danping Chen,Zhenchao Wang

N 6 -methyladenosine (m 6 A) is a crucial post-transcriptional epigenetic modification in RNAs which associates with numerous cancers development. Here, a cost-effective, and easy-to-operate fluorescence strategy for m 6 A analysis was developed based on the different cleavage efficiency of 8–17 DNAzyme for methylation and unmethylation sites. By arranging 8–17 DNAzyme to recognize and cleave 5'-rAG-3' and 5'-rm 6 AG-3' motifs in the target sequence respectively, various short ssDNA oligoes were produced, leaving different amounts of target sequence. Benefiting from the varying degrees of retardation of CHA amplification reaction, the tiny discrepancy between m 6 A and unmethylated adenine (A) can be distinguished. Moreover, we found that 8–17 DNAzyme was more sensitive to m 6 A than to A. Importantly, the strategy we proposed not only avoids sophisticated chemical labelling and expensive proteins, but also can be easily performed on the ordinary heating apparatus of accessible laboratory. The DCHA strategy demonstrated good analytical performance in complex biological matrices, and was successfully applied to hepatocellular carcinoma-related m 6 A analysis in CTNNB1, MGAT5 and SOCS-2 mRNAs with satisfactory results, showing its potential in clinical analysis.

研究领域: 分子生物学 · 生物化学 · 癌症生物学 · 表观遗传学
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Bioengineered · 2022 · IF 6.832

CircRNA CTNNB1 (circCTNNB1) ameliorates cerebral ischemia/reperfusion injury by sponging miR-96-5p to up-regulate scavenger receptor class B type 1 (SRB1) expression

Chun Chen,Xiaolong Chang,Shifei Zhang,Qi Zhao,Chunyan Lei

Emerging studies show that circRNA catenin beta 1 (circCTNNB1) plays a critical role in cancer. However, the expression and function of circCTNNB1 in cerebral ischemia/reperfusion injury (IRI) have not been reported. The present study discovered that circCTNNB1 and scavenger receptor class B type 1 (SRB1) expression levels were significantly down-regulated in mouse astrocytes (mAS) treated with oxygen glucose deprivation and reperfusion (OGD/R), and similar results were observed in a mouse middle cerebral artery occlusion model. Overexpression of circCTNNB1 alleviated cell apoptosis, oxidative stress and the inflammatory response induced by OGD/R in vitro. Up-regulation of circCTNNB1 increased SRB1 expression levels to protect mAS cells from OGD/R-induced damage. CircCTNNB1 and SRB1 interacted with miR-96-5p, and the overexpression of miR-96-5p efficiently reversed the function of circCTNNB1 in OGD/R-treated mAS cells. CircCTNNB1 protected against cerebral ischemia-reperfusion injury by up-regulating SRB1 in vivo. In conclusion, our findings suggest that circCTNNB1 acts as a competitive endogenous RNA for miR-96-5p to alleviate cerebral IRI, which provides novel evidence that circCTNNB1 and SRB1 may be biomarkers and therapeutic targets for cerebral IRI.

研究领域: 神经科学 · 分子生物学 · 细胞生物学
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Food Bioscience · 2025 · IF 5.9

Integrating zebrafish model and network pharmacology for screening and identification of edible herbs with therapeutic potential of anti-photoaging: A promising drug Gentiana rigescens Franch.

Ruoxin Chen,Jiahao Ren,Zhenlong Zhou,Wenjun Zhang,Jianyu Su

Gentiana rigescens Franch. extract have demonstrated various important bioactivities, however, their potential against photoaging has yet to be evaluated. This study explored the anti-photoaging effects of Gentiana rigescens Franch. root extract (GRFR) and stem (GRFS), along with their underlying mechanisms and bioactive components, using the UVB-induced zebrafish model. GRFS demonstrated superior anti-photoaging efficacy compared to GRFR. GRFS significantly alleviated UVB-induced tail fin damage, increasing the relative tail fin area from 31.23% to 80.92% (at 1mg/mL), and reducing ROS levels from 244.80% to 150.95%. It also inhibited lipid peroxidation, lowering malondialdehyde (MDA) levels from 202.87 nmol/g to 142.83 nmol/g. Furthermore, GRFS enhanced antioxidant enzyme activities, increasing superoxide dismutase (SOD) from 80.94 U/g to 104.06 U/g. Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) indicated substantial distinctions in the composition and content of major constituents between GRFR and GFRS, which may explain the differences in their anti-photoaging activities. And then network pharmacology was used to investigate possible mechanisms of GFRS, which identified five potential targets including CTNNB1, ESR1, AKT1, JUN and EGFR, as well as three key active compounds including aspartyl-phenylalanine (Asp-Phe), N-acetyl-L-phenylalanine (N-Acetyl-L-Phe), and phenylalanyl-tyrosine (Phe-Tyr). Finally, the molecular docking revealed that Phe-Tyr exhibited the strongest binding affinity for AKT1 (-8.86 kcal/mol), indicating that it may be the most potent anti-photoaging compound in GFRS. These findings suggest that G . rigescens , with its potent anti-photoaging properties, offers superior protection against UVB-induced photoaging and holds promise as a natural therapeutic agent.

研究领域: 药理学 · 植物学 · 皮肤科学 · 生物化学 · 计算生物学 · 天然产物研究 · 生物技术
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