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CTNNBIP1-CLSTN1作为一种管家嵌合RNA发挥作用,并通过SERPINE2调节细胞增殖。

CTNNBIP1-CLSTN1 Functions as a Housekeeping Chimeric RNA, and Regulates Cell Proliferation through SERPINE2.

作者信息

Li Hui, Chen Chen, Tang Yue, Qin Fujun, Singh Sandeep

机构信息

School of Basic Medical Sciences.

Zhengzhou University.

出版信息

Res Sq. 2023 Jul 17:rs.3.rs-3112431. doi: 10.21203/rs.3.rs-3112431/v1.

Abstract

The conventional wisdom that chimeric RNAs being peculiarity of carcinoma, and the products of chromosomal rearrangement is being challenged, However, experimental evidence supporting chimeric RNAs in normal physiology being functional is scarce. We decided to focus on one particular chimeric RNA, . We examined its expression among various tissues and cell types, and compared quantitatively among cancer and non-cancer cells. We further investigated its role in a panel of non-cancer cells and probed 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, stem, vascular endothelial cells, and hepatocytes. The expression level in non-cancerous cell lines is also not evidently different from that in the cancer cell lines. Furthermore, silencing significantly reduces cell proliferation rate, by inducing G2/M arrest in cell cycle progress and apoptosis in at least three cell types. Importantly, rescue experiments confirmed that the cell cycle arrest can be regained by exogenous expression of the chimera, but not the wild type parental gene. Further evidence is provided that regulates cell proliferation through . Thus, represents an example of a new class of fusion RNA, dubbed "housekeeping chimeric RNAs".

摘要

嵌合RNA是癌症特有的且是染色体重排产物这一传统观念正受到挑战。然而,支持正常生理状态下嵌合RNA具有功能的实验证据很少。我们决定聚焦于一种特定的嵌合RNA, 。我们检测了它在各种组织和细胞类型中的表达,并在癌细胞和非癌细胞之间进行了定量比较。我们进一步研究了它在一组非癌细胞中的作用,并探究了其功能机制。我们发现这种融合转录本在几乎所有组织以及包括成纤维细胞、上皮细胞、干细胞、血管内皮细胞和肝细胞在内的多种细胞类型中都有表达。在非癌细胞系中的表达水平与癌细胞系中的表达水平也没有明显差异。此外,沉默 可显著降低细胞增殖率,这是通过在细胞周期进程中诱导G2/M期阻滞以及在至少三种细胞类型中诱导凋亡来实现的。重要的是,拯救实验证实,通过外源表达嵌合体而非野生型亲本基因可恢复细胞周期阻滞。进一步的证据表明 通过 调节细胞增殖。因此, 代表了一类新的融合RNA的例子,被称为“管家嵌合RNA”。

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