CTNNBIP1-CLSTN1 functions as a housekeeping chimeric RNA and regulates cell proliferation through SERPINE2.
CTNNBIP1-CLSTN1 functions as a housekeeping chimeric RNA and regulates cell proliferation through SERPINE2.
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DOI：
10.1038/s41420-023-01668-8
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发表时间：
2023-10-07
影响因子：
7
通讯作者：
Li, Hui
中科院分区：
文献类型：
--
作者：
Chen, Chen;Qin, Fujun;Singh, Sandeep;Tang, Yue;Li, Hui
嵌合RNA是癌症特有的，是染色体重排的产物，这一传统理解正在受到挑战。然而，支持嵌合RNA在正常生理中的功能的实验证据很少。我们决定专注于一种特定的嵌合RNA，CTNNBIP1-CLSTN1。我们检测了它在不同组织和细胞类型中的表达，并对其在癌细胞和非癌细胞中的表达进行了定量比较。我们进一步研究了它在一组非肿瘤细胞中的作用，并探讨了其作用机制。我们发现这个融合转录本在几乎所有的组织和广泛的细胞类型中都有表达，包括成纤维细胞、上皮细胞、干细胞、血管内皮细胞和肝细胞。此外，CTNNBIP1-CLSTN1在非癌细胞系中的表达水平与在癌细胞系中的表达水平没有明显差异。此外，在至少三种细胞类型中，沉默CTNNBIP1-CLSTN1通过诱导G2/M期停滞和细胞凋亡而显著降低细胞增殖率。重要的是，救援实验证实，细胞周期停滞是通过嵌合体的外源表达恢复的，而不是野生型亲本基因。进一步的证据表明，CTNNBIP1-CLSTN1通过Serpine2调控细胞增殖。因此，CTNNBIP1-CLSTN1是一类新的融合RNAs的例子，被称为“管家嵌合RNAs”。
The conventional understanding that chimeric RNAs are unique to carcinoma and are the products of chromosomal rearrangement is being challenged. However, experimental evidence supporting the function of chimeric RNAs in normal physiology is scarce. We decided to focus on one particular chimeric RNA, CTNNBIP1-CLSTN1. We examined its expression in various tissues and cell types and compared it quantitatively among cancer and noncancer cells. We further investigated its role in a panel of noncancer cells and investigated the functional mechanism. We found that this fusion transcript is expressed in almost all tissues and a wide range of cell types, including fibroblasts, epithelial cells, stem cells, vascular endothelial cells, and hepatocytes. In addition, the CTNNBIP1-CLSTN1 expression level in noncancerous cell lines was not evidently different from that in cancer cell lines. Furthermore, in at least three cell types, silencing CTNNBIP1-CLSTN1 significantly reduced the cell proliferation rate by inducing G2/M arrest and apoptosis. Importantly, rescue experiments confirmed that cell cycle arrest was restored by exogenous expression of the chimera but not the wild-type parental gene. Further evidence is provided that CTNNBIP1-CLSTN1 regulates cell proliferation through SERPINE2. Thus, CTNNBIP1-CLSTN1 is an example of a new class of fusion RNAs, dubbed “housekeeping chimeric RNAs”.
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影响因子：
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发表时间：
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期刊：
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影响因子：
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作者：
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