更新于：2024-05-01

COL14A1

collagen type XIV alpha 1 chain

更新于：2024-05-01

基本信息

别名

COL14A1、Collagen alpha-1(XIV) chain、collagen type XIV alpha 1 chain

+ [2]

简介

Plays an adhesive role by integrating collagen bundles. It is probably associated with the surface of interstitial collagen fibrils via COL1. The COL2 domain may then serve as a rigid arm which sticks out from the fibril and protrudes the large N-terminal globular domain into the extracellular space, where it might interact with other matrix molecules or cell surface receptors (By similarity).

关联

100 项与 COL14A1 相关的临床结果

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100 项与 COL14A1 相关的转化医学

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0 项与 COL14A1 相关的专利（医药）

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170

项与 COL14A1 相关的文献（医药）

2024-02-02·Biomolecules

Identifying OGN as a Biomarker Covering Multiple Pathogenic Pathways for Diagnosing Heart Failure: From Machine Learning to Mechanism Interpretation.

Article

作者: Yihao Zhu ; Bin Chen ; Yao Zu

BACKGROUND:

The pathophysiologic heterogeneity of heart failure (HF) necessitates a more detailed identification of diagnostic biomarkers that can reflect its diverse pathogenic pathways.

METHODS:

We conducted weighted gene and multiscale embedded gene co-expression network analysis on differentially expressed genes obtained from HF and non-HF specimens. We employed a machine learning integration framework and protein-protein interaction network to identify diagnostic biomarkers. Additionally, we integrated gene set variation analysis, gene set enrichment analysis (GSEA), and transcription factor (TF)-target analysis to unravel the biomarker-dominant pathways. Leveraging single-sample GSEA and molecular docking, we predicted immune cells and therapeutic drugs related to biomarkers. Quantitative polymerase chain reaction validated the expressions of biomarkers in the plasma of HF patients. A two-sample Mendelian randomization analysis was implemented to investigate the causal impact of biomarkers on HF.

RESULTS:

We first identified COL14A1, OGN, MFAP4, and SFRP4 as candidate biomarkers with robust diagnostic performance. We revealed that regulating biomarkers in HF pathogenesis involves TFs (BNC2, MEOX2) and pathways (cell adhesion molecules, chemokine signaling pathway, cytokine-cytokine receptor interaction, oxidative phosphorylation). Moreover, we observed the elevated infiltration of effector memory CD4+ T cells in HF, which was highly related to biomarkers and could impact immune pathways. Captopril, aldosterone antagonist, cyclopenthiazide, estradiol, tolazoline, and genistein were predicted as therapeutic drugs alleviating HF via interactions with biomarkers. In vitro study confirmed the up-regulation of OGN as a plasma biomarker of HF. Mendelian randomization analysis suggested that genetic predisposition toward higher plasma OGN promoted the risk of HF.

CONCLUSIONS:

We propose OGN as a diagnostic biomarker for HF, which may advance our understanding of the diagnosis and pathogenesis of HF.

2023-10-30·Scientific reports

Primary breast tumor induced extracellular matrix remodeling in premetastatic lungs.

Article

作者: Ruoqing Cai ; Caitlin M Tressler ; Menglin Cheng ; Kanchan Sonkar ; Zheqiong Tan ; Santosh Kumar Paidi ; Vinay Ayyappan ; Ishan Barman ; Kristine Glunde

The premetastatic niche hypothesis proposes an active priming of the metastatic site by factors secreted from the primary tumor prior to the arrival of the first cancer cells. We investigated several extracellular matrix (ECM) structural proteins, ECM degrading enzymes, and ECM processing proteins involved in the ECM remodeling of the premetastatic niche. Our in vitro model consisted of lung fibroblasts, which were exposed to factors secreted by nonmalignant breast epithelial cells, nonmetastatic breast cancer cells, or metastatic breast cancer cells. We assessed ECM remodeling in vivo in premetastatic lungs of female mice growing orthotopic primary breast tumor xenografts, as compared to lungs of control mice without tumors. Premetastatic lungs contained significantly upregulated Collagen (Col) Col4A5, matrix metalloproteinases (MMPs) MMP9 and MMP14, and decreased levels of MMP13 and lysyl oxidase (LOX) as compared to control lungs. These in vivo findings were consistent with several of our in vitro cell culture findings, which showed elevated Col14A1, Col4A5, glypican-1 (GPC1) and decreased Col5A1 and Col15A1 for ECM structural proteins, increased MMP2, MMP3, and MMP14 for ECM degrading enzymes, and decreased LOX, LOXL2, and prolyl 4-hydroxylase alpha-1 (P4HA1) for ECM processing proteins in lung fibroblasts conditioned with metastatic breast cancer cell media as compared to control. Taken together, our data show that premetastatic priming of lungs by primary breast tumors resulted in significant ECM remodeling which could facilitate metastasis by increasing interstitial fibrillar collagens and ECM stiffness (Col14A1), disruptions of basement membranes (Col4A5), and formation of leaky blood vessels (MMP2, MMP3, MMP9, and MMP14) to promote metastasis.

2023-10-16·Cancer letters

Hypoxia-induced circ-CDYL-EEF1A2 transcriptional complex drives lung metastasis of cancer stem cells from hepatocellular carcinoma.

Article

作者: Ruijiao Kong ; Wenxin Wei ; Qiuhong Man ; Liang Chen ; Yin Jia ; Hui Zhang ; Zixin Liu ; Kai Cheng ; Chuanbin Mao ; Shanrong Liu

Hepatocellular carcinoma (HCC) is often associated with poor outcomes due to lung metastasis. ICAM-1⁺ circulating tumor cells, termed circulating cancer stem cells (CCSCs), possess stem cell-like characteristics. However, it is still unexplored how their presence indicates lung metastasis tendency, and particularly, what mechanism drives their lung metastasis. Here, we demonstrated that a preoperative CCSC count in 5 mL of blood (CCSC⁵) of >3 was a risk factor for lung metastasis in clinical HCC patients. The CSCs overexpressed with circ-CDYL entered the bloodstream and developed lung metastases in mice. Mechanistically, circ-CDYL promoted COL14A1 expression and thus ERK signaling to facilitate epithelial-mesenchymal transition. Furthermore, we uncovered that an RNA-binding protein, EEF1A2, acted as a novel transcriptional (co-) factor to cooperate with circ-CDYL and initiate COL14A1 transcription. A high circ-CDYL level is caused by HIF-1⍺-mediated transcriptional upregulation of its parental gene CDYL and splicing factor EIF4A3 under a hypoxia microenvironment. Hence, the hypoxia microenvironment enables the high-tendency lung metastasis of ICAM-1⁺ CCSCs through the HIF-1⍺/circ-CDYL-EEF1A2/COL14A1 axis, potentially allowing clinicians to preoperatively detect ICAM-1⁺ CCSCs as a real-time biomarker for precisely deciding HCC treatment strategies.

项与 COL14A1 相关的新闻（医药）

2024-02-22

·今日头条

【Nature子刊】中国医学科学院北京协和医学院王冬来团队：揭示调节肺癌转移新机制

本文为转化医学网原创，转载请注明出处作者：Sophia 导读：转移是肺癌相关死亡的主要原因，但控制肺肿瘤转移的机制仍未完全阐明。SE 易位（SET）在肺肿瘤中过表达，并与不良预后相关。 2024年2月14日，中国医学科学院北京协和医学院基础医学研究所王冬来课题组在《Nature Communications》上发表题为“Oncoprotein SET-associated transcription factor ZBTB11 triggers lung cancer metastasis”的研究文章，研究证明了 ZBTB11 是一种关键的转移调节因子，并揭示了 ZBTB11 调节肺肿瘤转移的多种机制。 https://www-nature-com.libproxy1.nus.edu.sg/articles/s41467-024-45585-5 研究背景 01 最新的全球癌症统计数据显示，虽然肺癌发病率已降至第二位，但仍然是癌症死亡的主要原因。肺癌在组织学上可分为小细胞肺癌（SCLC）和非小细胞肺癌（NSCLC），后者可进一步分为腺癌（LUAD）、鳞状细胞癌（LUSC）、大细胞癌等。在所有类型的肺癌中，超过40%是腺癌，转移是恶性肿瘤晚期的标志，是患者肺癌相关死亡的主要原因。然而，肺癌转移的调控机制仍不完全清楚。癌蛋白 SET 最初是在急性未分化白血病（AUL）研究中发现的，在研究染色体易位引起的 DNA 断点时发现了一种新的致癌 SET-CAN 融合基因。条件基因敲除小鼠模型中 SET 表达的完全丧失揭示了胚胎致死表型，证明了 SET 在调节正常发育中的关键作用。更引人注目的是，SET过表达是包括肺癌在内的不同类型癌症中的常见事件，这表明SET在成体细胞中的异常表达有助于肿瘤的发生和/或进展。通过单独或联合策略靶向异常 SET 可能会触发细胞质和细胞核参与的肿瘤机制，包括肺癌，干预。然而，决定 SET 用于肺癌转移调节的细胞核内的主要 TFs 仍然不明确。据报道，ZBTB11 参与了长链非编码 RNA （lncRNA） DUBR 介导的肺癌细胞迁移和侵袭，这表明 ZBTB11 在肺癌进展过程中具有潜在作用。然而， ZBTB11 在肺癌中控制的精确转录谱、调控网络和生物学后果在很大程度上仍然未知。研究进展 02 为了研究肺癌细胞中 SET 和 ZBTB11 之间的功能相互作用，我们试图鉴定 SET 介导的 ZBTB11 直接靶基因的调控。为此，我们首先在SET耗竭96小时后通过RNA-seq评估H1299细胞中的差异表达基因（图3a）。如图 3b 所示，我们鉴定了 164 和 145 个基因，它们在 SET 敲低时分别上调和下调。同样，大多数SET调节的基因也富集在蛋白质编码类别中（~67%，207，图3c）。基于这些数据集，我们发现了 35 个推定的 ZBTB11 直接靶基因，这些基因受 SET（图3d）的共调控。有趣的是，这些基因可以清楚地分为两组：18 个基因在 SET 和 ZBTB11 耗竭时被转录抑制，17 个基因在 SET 和 ZBTB11 耗竭时被转录激活（图3e）。SET/ZBTB11 共调控靶基因的转录谱表明 SET 可能与 ZBTB11 在转录调控方面具有功能协同作用。值得注意的是，GO分析显示，由共调控靶基因富集的顶级生物过程是“细胞外基质组织”，与ZBTB11调控基因富集的生物过程完全相同（图3f）。此外，使用靶标特异性引物的RT-qPCR测定进一步证实，参与细胞外基质组织的MMP9、MMP19、SPARC、PECAM1、SPP1和COL14A1基因确实在H1299细胞中受到SET和ZBTB11的共同调节（图3g）。在 H1975 肺癌细胞中，这些基因在 SET 和/或 ZBTB11 敲低时的类似转录调控也被概括。 SET与ZBTB11在转录调控方面合作总的来说，这些数据表明 SET 与 ZBTB11 在转录调控中合作，并促使我们关注 SET-ZBTB11 蛋白复合物在肿瘤发生和进展时调节细胞外基质相关生物过程的潜在作用。研究结果 03 在这项研究中，我们将 ZBTB11 确定为细胞核中癌蛋白 SET 的结合伙伴。对 ChIP-seq 和 RNA-seq 的综合分析表明，ZBTB11 在肺癌细胞中充当转录因子。SET通过作为辅因子与ZBTB11合作进行转录调控，SET和ZBTB11之间的相互作用在调节肺癌细胞的转移行为中至关重要。从机制上讲，我们发现 MMP9 是有助于 SET-ZBTB11 复合物介导的转移调节的主要下游效应子。此外，ZBTB11 通过转录抑制 PRRG2 表现出一种作用模式，与 YAP1 的激活建立连接，以 SET-ZBTB11 复合物非依赖性方式促进肺肿瘤转移。更重要的是，ZBTB11的条件性敲除可显著抑制体内遗传病变诱导的原发性肺肿瘤的远端转移。综上所述，我们的研究表明，SET结合伙伴ZBTB11在调节肺肿瘤转移中起着关键作用。参考资料： https://www-nature-com.libproxy1.nus.edu.sg/articles/s41467-024-45585-5 注：本文旨在介绍医学研究进展，不能作为治疗方案参考。如需获得健康指导，请至正规医院就诊。热门·直播/活动 🕓 上海｜3月01日-02日 ▶第三届长三角单细胞组学技术应用论坛暨空间组学前沿论坛将在上海召开，诚邀您的参与！点击对应文字查看详情

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