RB1 5'UTR 含有与细胞周期控制和癌症进展相关的 IRES。

RB1 5́UTR contains an IRES related to cell cycle control and cancer progression.

机构信息

Changzhou Capmus of Hohai University, Changzhou, Jiangsu Province 213022, PR China.

Nanjing Kingsley Biotechnology Co., Ltd, Nanjing, Jiangsu Province 210000, PR China.

出版信息

Gene. 2023 Dec 15;887:147724. doi: 10.1016/j.gene.2023.147724. Epub 2023 Aug 19.

DOI:10.1016/j.gene.2023.147724

PMID:37604323

Abstract

Retinoblastoma gene1 (RB1) is the first tumor suppressor gene that stands as the guardian of the gate of the G period and plays a central role in proliferation and differentiation. However, no reports focused on the possible internal ribosome entry site (IRES) function of the RB1 gene flanking sequence. In this study, we constructed a bicistronic reporter with the RB1 5'untranslated region (5́UTR) inserted between two reporter coding regions. We found RB1 5'UTR harbors an IRES and has higher activity in cancer cell lines than normal cells. Besides, RB1 IRES acquired the highest activity in the G/G phase of the cell cycle, and the RB1 5'UTR mutation collected from retinoblastoma decreased IRES activity compared with RB1 5'UTR wild-type. These data indicated that RB1 IRES is a mechanism of stress regulation and is related to cell cycle control and cancer progression.

摘要

视网膜母细胞瘤基因 1（RB1）是第一个肿瘤抑制基因，作为 G 期大门的守护者，在增殖和分化中发挥核心作用。然而，目前尚无研究关注 RB1 基因侧翼序列中可能存在的内部核糖体进入位点（IRES）功能。在这项研究中，我们构建了一个双顺反子报告基因，其中 RB1 的 5′非翻译区（5′UTR）插入两个报告基因编码区之间。我们发现 RB1 5′UTR 含有一个 IRES，并且在癌细胞系中的活性高于正常细胞。此外，RB1 IRES 在细胞周期的 G1/G0 期具有最高的活性，而从视网膜母细胞瘤中收集的 RB1 5′UTR 突变与 RB1 5′UTR 野生型相比降低了 IRES 的活性。这些数据表明，RB1 IRES 是一种应激调节机制，与细胞周期控制和癌症进展有关。