更新于：2024-05-01

CNN1

calponin 1

更新于：2024-05-01

基本信息

别名

Basic calponin、calponin 1、Calponin H1, smooth muscle

+ [4]

简介

Thin filament-associated protein that is implicated in the regulation and modulation of smooth muscle contraction. It is capable of binding to actin, calmodulin and tropomyosin. The interaction of calponin with actin inhibits the actomyosin Mg-ATPase activity (By similarity).

关联

100 项与 CNN1 相关的临床结果

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100 项与 CNN1 相关的转化医学

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0 项与 CNN1 相关的专利（医药）

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273

项与 CNN1 相关的文献（医药）

2024-01-17·Aging

Long non-coding RNA MEG3 acts as a suppressor in breast cancer by regulating miR-330/CNN1.

Article

作者: Dandan Yi ; Zetian Wang ; Haojie Yang ; Ru Wang ; Xianbiao Shi ; Zhijian Liu ; Fazhan Xu ; Qing Lu ; Xiao Chu ; Jianfeng Sang

BACKGROUND:

The current study aimed to investigate the molecular mechanism of long non-coding RNA (lncRNA) MEG3 in the development of breast cancer.

METHODS:

The regulating relationships among lncRNA MEG3, miRNA-330 and CNN1 were predicted by bioinformatics analysis of breast cancer samples in the Cancer Genome Atlas database. The differential expression of lncRNA MEG3, miRNA-330 and CNN1 was first validated in breast cancer tissues and cells. The effects of lncRNA MEG3 on breast cancer malignant properties were evaluated by manipulating its expression in MCF-7 and BT-474 cells. Rescue experiments, dual-luciferase assays, and RNA immunoprecipitation (RIP) experiments were further used to validate the relationships among lncRNA MEG3, miRNA-330 and CNN1.

RESULTS:

Bioinformatics analysis showed that lncRNA MEGs and CNN1 were significantly downregulated in breast cancer tissues, while miR-330 was upregulated. These differential expressions were further validated in our cohort of breast cancer samples. High expression levels of lncRNA MEG3 and CNN1 as well as low expression of miR-330 were significantly associated with favorable overall survival. Overexpression of lncRNA MEG3 significantly inhibited cell viability, migration and invasion, decreased cells in S stage and promoted cell apoptosis. Dual-luciferase reporter gene assay and RIP experiments showed that lncRNA MEG3 could directly bind to miR-330. Moreover, miR-330 mimics on the basis of lncRNA MEG3 overexpression ameliorated the tumor-suppressing effects of lncRNA MEG3 in breast cancer malignant properties by decreasing CNN1 expression.

CONCLUSION:

Our study indicated lncRNA MEG3 is a breast cancer suppressor by regulating miR-330/CNN1 axis.

2023-12-29·Journal of the European Academy of Dermatology and Venereology : JEADV

Consistency of convolutional neural networks in dermoscopic melanoma recognition: A prospective real-world study about the pitfalls of augmented intelligence.

Article

作者: E V Goessinger ; S E Cerminara ; A M Mueller ; P Gottfrois ; S Huber ; M Amaral ; F Wenz ; L Kostner ; L Weiss ; M Kunz ; J-T Maul ; S Wespi ; E Broman ; S Kaufmann ; V Patpanathapillai ; I Treyer ; A A Navarini ; L V Maul

BACKGROUND:

Deep-learning convolutional neural networks (CNNs) have outperformed even experienced dermatologists in dermoscopic melanoma detection under controlled conditions. It remains unexplored how real-world dermoscopic image transformations affect CNN robustness.

OBJECTIVES:

To investigate the consistency of melanoma risk assessment by two commercially available CNNs to help formulate recommendations for current clinical use.

METHODS:

A comparative cohort study was conducted from January to July 2022 at the Department of Dermatology, University Hospital Basel. Five dermoscopic images of 116 different lesions on the torso of 66 patients were captured consecutively by the same operator without deliberate rotation. Classification was performed by two CNNs (CNN-1/CNN-2). Lesions were divided into four subgroups based on their initial risk scoring and clinical dignity assessment. Reliability was assessed by variation and intraclass correlation coefficients. Excisions were performed for melanoma suspicion or two consecutively elevated CNN risk scores, and benign lesions were confirmed by expert consensus (n = 3).

RESULTS:

117 repeated image series of 116 melanocytic lesions (2 melanomas, 16 dysplastic naevi, 29 naevi, 1 solar lentigo, 1 suspicious and 67 benign) were classified. CNN-1 demonstrated superior measurement repeatability for clinically benign lesions with an initial malignant risk score (mean variation coefficient (mvc): CNN-1: 49.5(±34.3)%; CNN-2: 71.4(±22.5)%; p = 0.03), while CNN-2 outperformed for clinically benign lesions with benign scoring (mvc: CNN-1: 49.7(±22.7)%; CNN-2: 23.8(±29.3)%; p = 0.002). Both systems exhibited lowest score consistency for lesions with an initial malignant risk score and benign assessment. In this context, averaging three initial risk scores achieved highest sensitivity of dignity assessment (CNN-1: 94%; CNN-2: 89%). Intraclass correlation coefficients indicated 'moderate'-to-'good' reliability for both systems (CNN-1: 0.80, 95% CI:0.71-0.87, p < 0.001; CNN-2: 0.67, 95% CI:0.55-0.77, p < 0.001).

CONCLUSIONS:

Potential user-induced image changes can significantly influence CNN classification. For clinical application, we recommend using the average of three initial risk scores. Furthermore, we advocate for CNN robustness optimization by cross-validation with repeated image sets.

TRIAL REGISTRATION:

ClinicalTrials.gov (NCT04605822).

2023-12-26·Journal of cellular and molecular medicine

Calponin 1 inhibits agonist-induced ERK activation and decreases calcium sensitization in vascular smooth muscle.

Article

作者: Lova Prasadareddy Kajuluri ; Qing Rex Lyu ; Jaser Doja ; Ajay Kumar ; Michael P Wilson ; Samantha R Sgrizzi ; Elika Rezaeimanesh ; Joseph M Miano ; Kathleen G Morgan

Smooth muscle cell (SMC) contraction and vascular tone are modulated by phosphorylation and multiple modifications of the thick filament, and thin filament regulation of SMC contraction has been reported to involve extracellular regulated kinase (ERK). Previous studies in ferrets suggest that the actin-binding protein, calponin 1 (CNN1), acts as a scaffold linking protein kinase C (PKC), Raf, MEK and ERK, promoting PKC-dependent ERK activation. To gain further insight into this function of CNN1 in ERK activation and the regulation of SMC contractility in mice, we generated a novel Calponin 1 knockout mouse (Cnn1 KO) by a single base substitution in an intronic CArG box that preferentially abolishes expression of CNN1 in vascular SMCs. Using this new Cnn1 KO mouse, we show that ablation of CNN1 has two effects, depending on the cytosolic free calcium level: (1) in the presence of elevated intracellular calcium caused by agonist stimulation, Cnn1 KO mice display a reduced amplitude of stress and stiffness but an increase in agonist-induced ERK activation; and (2) during intracellular calcium depletion, in the presence of an agonist, Cnn1 KO mice exhibit increased duration of SM tone maintenance. Together, these results suggest that CNN1 plays an important and complex modulatory role in SMC contractile tone amplitude and maintenance.

项与 CNN1 相关的新闻（医药）

2023-03-24

·生物谷

CCR：科学家首次发现，耐药卵巢癌能细胞“催眠”同伙，促进周围癌细胞集体耐药！

这项研究报告了一种新的化疗耐药机制，即化疗可促进静止态卵巢癌细胞表达大量FST，并以旁分泌的方式影响其邻近肿瘤细胞的增殖和耐药。通过敲除FST或使用FST中和抗体可提高肿瘤细胞或小鼠肿瘤模型对化疗药物卵巢癌是女性常见恶性肿瘤之一。由于卵巢位于盆腔较深部，缺乏早期筛查方法，多数患者确诊时已是晚期，具有病程复杂，易复发，远期生存率低等特点。因此，卵巢癌成为了女性生殖道肿瘤诊治中的“硬骨头”。手术和化疗是卵巢癌的常规治疗手段，其中约70%的患者经化疗后能够实现缓解，但大部分患者仍会对化疗药物耐药，最终导致卵巢癌治疗失败，但目前尚无较好的方法可以解决耐药问题。不过近日，美国匹兹堡大学Ronald Buckanovich教授团队发表于癌症领域著名期刊Clinical Cancer Research的最新研究[1]，为克服卵巢癌耐药带来了希望。该研究发现，化疗可通过激活转录因子NFATC4，使静止态卵巢癌细胞分泌大量卵泡抑制素（follistatin, FST），从而促进周围肿瘤细胞耐药；而靶向FST在临床前研究中逆转了卵巢癌细胞的耐药，并提高了卵巢癌小鼠模型的存活率和生存期。文章首页截图在肿瘤中，有部分暂停增殖、处于G0期的细胞，被称为静止态癌细胞。由于化疗主要针对快速分裂的细胞，静止态癌细胞由于分裂缓慢而对化疗药物耐受，既往研究已经证明，静止态癌细胞在多种癌症的耐药中扮演了重要角色[2]。静止态癌细胞在卵巢癌的化疗耐药中也起到重要作用[3]。Buckanovich教授团队在此前的工作中发现，转录因子NFATC4在卵巢癌肿瘤干细胞中高表达，化疗可激活NFATC4入核促进其发挥转录调控作用[4]，从而诱导细胞进入静止状态并发生耐药。但是，其中的具体机制尚不清楚。因此，研究团队这次首先通过体外实验，鉴定出受NFATC4调控的141个靶基因，其中RCAN1, CNN1, COL3A1, FST和ANO1的mRNA表达量上调最为明显。考虑到FST在卵巢的发育和功能中具有重要作用[5]，并且临床发现卵巢癌患者血清中的FST也出现升高[6]，研究团队决定探索NFATC4下游靶点FST的作用。体外细胞实验证实，NFATC4确实能调控FST蛋白表达，且对高级别浆液性卵巢癌（HGSOC）患者肿瘤组织中，不同分裂速度的癌细胞进行比较时，发现静止态癌细胞中FST表达量显著增高（P<0.01），可达到快速分裂细胞的23倍，由此可见，NFATC4对FST的调控作用主要发生于静止态肿瘤细胞中。用化疗药物顺铂或紫杉醇处理不同卵巢癌细胞系，可导致FST的mRNA表达量增加10-72倍，导致FST的蛋白表达量增加4-50倍，且静止态癌细胞是FST增加的主要来源，这部分细胞的FST分泌量大约是正常分裂癌细胞的3倍。不同化疗药物（紫杉醇，Taxol；顺铂，Ciplatin）处理后不同卵巢癌细胞系FST分泌量的变化情况同时，在卵巢癌肿瘤模型小鼠上也观察到化疗促进FST分泌的现象。那么这些大量分泌的FST，到底有什么用呢？研究显示，高浓度FST处理可导致体外培养的卵巢癌细胞数量明显减少（P<0.001）；进一步的分析发现，FST对细胞生长的影响是由于抑制增殖，且仅对快速分裂的细胞增殖产生明显作用，并不影响静止态癌细胞。不同浓度FST对不同卵巢癌细胞生长的影响前面提到过，许多化疗药物主要针对的是快速分裂的癌细胞，而一旦细胞增殖速度减慢，药效肯定会大打折扣！果然，研究团队发现FST能促进化疗耐药：与单独使用紫杉醇相比，联合FST处理时肿瘤细胞存活数量可提高1.5-2.5倍（P<0.05）。使用顺铂进行实验也得到相似结果，机制分析则显示，FST可通过ATF2信号转导通路促进化疗耐药。值得一提的是，研究者们还通过细胞共培养实验证明，静止态癌细胞产生的FST可以旁分泌的方式，抑制其邻近快速分裂癌细胞的增殖。打个比方来说，静止态癌细胞就像花的花芯，而相邻的细胞就像花瓣，当化疗药物来袭时，静止态癌细胞就分泌FST来保护整个“花朵”。在此过程中，更多的肿瘤细胞会进入静止状态，并进一步影响其周围更多的细胞，越来越多的耐药细胞也就随之产生，最终导致癌症复发。 FST可促进化疗药物（紫杉醇，Taxol；顺铂，Cisplatin）发生耐药接下来，研究团队尝试将FST作为治疗靶点，使用FST中和抗体或CRISPR-Cas9敲除FST，均能显著增加卵巢癌细胞对化疗药物的敏感性（P<0.01）；而为进一步评估敲除FST在体内的作用，研究者建立了卵巢癌移植瘤小鼠模型，并用紫杉醇进行治疗，结果显示，相比野生型小鼠，注射FST-KO细胞的小鼠存活率显著提高（P<0.0001），总生存期也明显延长。在化疗药物治疗同时FST敲除对移植瘤小鼠存活率和生存期的影响最后，研究团队还比较了化疗前后卵巢癌患者体内FST的变化情况：与化疗前相比，患者FST水平在化疗后24小时后增加了1-3倍；而对数百名卵巢癌患者的TCGA数据分析发现，高水平FST与较低的生存率相关，表明FST也有望作为逆转人卵巢癌耐药的新靶点。总的来说，这项研究报告了一种新的化疗耐药机制，即化疗可促进静止态卵巢癌细胞表达大量FST，并以旁分泌的方式影响其邻近肿瘤细胞的增殖和耐药。通过敲除FST或使用FST中和抗体可提高肿瘤细胞或小鼠肿瘤模型对化疗药物的敏感性。 FST介导的卵巢癌化疗耐药模式图本次研究对卵巢癌的治疗具有重要意义，化疗目前仍是不可手术卵巢癌的有效治疗手段，减少耐药和复发将大大改善患者预后，而且FST是一种分泌性蛋白，因此是中和抗体的理想靶点，期待相关抗体药物能早日被成功研发出来。