The BAP31/miR-181a-5p/RECK axis promotes angiogenesis in colorectal cancer via fibroblast activation.
The BAP31/miR-181a-5p/RECK axis promotes angiogenesis in colorectal cancer via fibroblast activation.
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DOI：
10.3389/fonc.2023.1056903
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发表时间：
2023
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
b细胞受体相关蛋白31 （BAP31）已被认为是一种肿瘤相关蛋白，并在很大程度上被证明可促进多种癌症的转移。肿瘤转移的发生有多个步骤，血管生成的诱导被认为是肿瘤转移过程中的一个限速步骤。本研究探讨BAP31通过调节肿瘤微环境对结直肠癌血管生成的影响。首先，来自bap31调控的crc的外泌体在体内和体外影响正常成纤维细胞向促血管生成癌症相关成纤维细胞（CAFs）的转变。接下来，进行microRNA测序，分析BAP31-过表达的crc分泌的外泌体的microRNA表达谱。结果表明，BAP31在crc中的表达显著改变了外泌体microrna的水平，如miR-181a- 5p。同时，体外成管实验显示，高水平miR-181a-5p的成纤维细胞显著促进内皮细胞血管生成。至关重要的是，我们首先使用双荧光素酶活性测定法确定了miR-181a-5p直接靶向具有卡扎尔基序（RECK）的逆转诱导半胱氨酸富蛋白的3'-非翻译区（3 ' utr），通过上调基质金属蛋白酶-9 （MMP-9）和母亲抗十五肢瘫痪同源物2/母亲抗十五肢瘫痪同源物3 （Smad2/3）的磷酸化，驱动成纤维细胞转化为促血管生成CAFs。发现来自bap31过表达/ bap31敲低的crc的外泌体通过miR-181a-5p/RECK轴操纵成纤维细胞向促血管生成CAFs的转变。
B-cell receptor–associated protein 31 (BAP31) has been recognized as a tumor-associated protein and has largely been shown to promote metastasis in a variety of cancers. Cancer metastasis arises through multistep pathways, and the induction of angiogenesis is shown to be a rate-limiting step in the process of tumor metastasis. This study explored the effect of BAP31 on colorectal cancer (CRC) angiogenesis by regulating the tumor microenvironment. First, exosomes from BAP31-regulated CRCs affected the transition of normal fibroblasts to proangiogenic cancer-associated fibroblasts (CAFs) in vivo and in vitro. Next, microRNA sequencing was performed to analyze the microRNA expression profile of exosomes secreted from BAP31- overexpressing CRCs. The results indicated that the expression of BAP31 in CRCs significantly altered the levels of exosomal microRNAs, such as miR-181a- 5p. Meanwhile, an in vitro tube formation assay showed that fibroblasts with high levels of miR-181a-5p significantly promoted endothelial cell angiogenesis. Critically, we first identified that miR-181a-5p directly targeted the 3'-untranslated region (3′UTR) of reversion-inducing cysteine-rich protein with kazal motifs (RECK) using the dual-luciferase activity assay, which drove fibroblast transformation into proangiogenic CAFs by upregulating matrix metalloproteinase-9 (MMP-9) and phosphorylation of mothers against decapentaplegic homolog 2/Mothers against decapentaplegic homolog 3 (Smad2/3). Exosomes from BAP31-overexpressing/BAP31-knockdown CRCs are found to manipulate the transition of fibroblasts into proangiogenic CAFs by the miR-181a-5p/RECK axis.
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DOI：
10.1146/annurev.pathol.4.110807.092222
发表时间：
2009
期刊：
Annual review of pathology
影响因子：
--
作者：
Lee YS;Dutta A
通讯作者：
Dutta A
影响因子：
5.6
作者：
Kasprzak A
通讯作者：
Kasprzak A
影响因子：
16.2
作者：
Cho C;Smallwood PM;Nathans J
通讯作者：
Nathans J
影响因子：
37.3
作者：
Liu K;Xie F;Gao A;Zhang R;Zhang L;Xiao Z;Hu Q;Huang W;Huang Q;Lin B;Zhu J;Wang H;Que J;Lan X
通讯作者：
Lan X
影响因子：
11.2
作者：
Li Y;Kuscu C;Banach A;Zhang Q;Pulkoski-Gross A;Kim D;Liu J;Roth E;Li E;Shroyer KR;Denoya PI;Zhu X;Chen L;Cao J
通讯作者：
Cao J