BAP31-Mediated miR-206/133b Cluster Promotes Transendothelial Migration and Metastasis of Colorectal Cancer.
BAP31-Mediated miR-206/133b Cluster Promotes Transendothelial Migration and Metastasis of Colorectal Cancer.
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DOI：
10.3390/ijms242316740
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发表时间：
2023-11-25
影响因子：
5.6
通讯作者：
Wang, Bing
中科院分区：
文献类型：
--
作者：
Zhang, Qi;Wang, Changli;Wu, Yufei;Liu, Jingjing;Wang, Tianyi;Wang, Bing
失调的B细胞受体相关蛋白31（BAP 31）在肿瘤进展中起着至关重要的作用。本研究旨在探讨BAP 31对结直肠癌（CRC）中miR-206/133 b簇的作用及其分子机制。进行qPCR以检测组织和细胞中的miRNA和mRNA水平。使用蛋白质印迹分析来评估生物标志物和靶标的水平，以及BAP 31和HOXD 10的水平。进行伤口愈合、共培养和transwell测定以评估CRC细胞的跨内皮迁移能力。采用荧光素酶测定来评估miRNA对靶标的结合作用，以及基因组片段的起始转录作用。通过体内动物研究建立肿瘤生长和肺转移模型。BAP 31在CRC细胞中的过表达导致miR-206/133 b簇的表达减少。miR-206/133 b簇的表达与CRC细胞的跨内皮迁移能力相关。发现miR-206/133 b簇在紧密连接途径（hsa 04530）中直接调节细胞分裂周期42（CDC 42）和肌动蛋白相关蛋白2/3复合物亚基5（ARPC 5）。此外，还发现miR-206/133 b簇的潜在转录调节因子是同源框D10（HOXD 10）。我们进一步阐明了BAP 31通过抑制HOXD 10从细胞质向细胞核的转位来调节miR-206/133 b簇表达水平的分子机制和功能机制。总之，这项研究为BAP 31如何调节miR-206/133 b簇的转录以及BAP 31相关的肺转移如何在CRC中出现提供了有价值的见解。
Dysregulated B cell receptor-associated protein 31 (BAP31) plays a crucial role in tumor progression. This study aimed to investigate the functions and molecular mechanism of BAP31 on the miR-206/133b cluster in colorectal cancer (CRC). qPCR was conducted to detect miRNA and mRNA levels in tissues and cells. Western blot assays were used to assess the levels of biomarkers and targets, as well as the levels of BAP31 and HOXD10. Wound healing, coculture and transwell assays were conducted to assess the transendothelial migration abilities of CRC cells. A luciferase assay was employed to assess miRNA binding effects on targets, as well as the initiating transcription effect of genomic fragments. Tumor growth and lung metastatic models were established through an in vivo animal study. BAP31 overexpression in CRC cells led to a reduction in the expression of the miR-206/133b cluster. The expression of the miR-206/133b cluster was correlated with the transendothelial migration capability of CRC cells. The miR-206/133b cluster was found to directly regulate cell division cycle 42 (CDC42) and actin-related protein 2/3 complex subunit 5 (ARPC5) in the tight junction pathway (hsa04530). Moreover, a potential transcription regulator of the miR-206/133b cluster was also found to be Homeobox D10 (HOXD10). We further elucidated the molecular mechanisms and functional mechanisms of BAP31’s regulatory role in the expression levels of the miR-206/133b cluster by inhibiting HOXD10 translocation from the cytoplasm to the nucleus. In conclusion, this study provides valuable insights into how BAP31 regulates the transcription of the miR-206/133b cluster and how BAP31-related lung metastases arise in CRC.
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癌症中的microRNA生物发生途径。
DOI：
10.1038/nrc3932
发表时间：
2015-06
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Lin S;Gregory RI
通讯作者：
Gregory RI
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影响因子：
5.8
作者：
Hua, Xu;Chen, Luxiao;Wingender, Edgar
通讯作者：
Wingender, Edgar
影响因子：
14.9
作者：
Mendes ND;Freitas AT;Sagot MF
通讯作者：
Sagot MF
mirTrans：人类细胞系 microRNA 转录调控的资源
影响因子：
14.9
作者：
Hua X;Tang R;Xu X;Wang Z;Xu Q;Chen L;Wingender E;Li J;Zhang C;Wang J
通讯作者：
Wang J
影响因子：
5.6
作者：
Matoušková P;Hanousková B;Skálová L
通讯作者：
Skálová L