关键词: ALDH1A3 Bladder cancer Chemical carcinogenesis CircLMBR1 High-throughput sequencing

来  源:   DOI:10.1016/j.ncrna.2024.05.004   PDF(Pubmed)

Abstract:
UNASSIGNED: Circular RNAs (circRNAs) have been identified as playing an integral role in the development of bladder cancer (BC). However, the mechanism by which circRNAs operate in the chemical carcinogenesis of BC remains unclear.
UNASSIGNED: To explore this mechanism, we used RNA high-throughput sequencing to identify differentially expressed circRNA in bladder epithelial cells and chemically induced malignant transformed BC cells. Subsequently, in vitro experiments were conducted to investigate the biological function and molecular mechanism of circLMBR1 in BC. Finally, animal experiments were conducted to examine the clinical relevance of circLMBR1 in vivo.
UNASSIGNED: Our profiling of circular RNA expression during cellular malignant transformation induced by chemical carcinogens identified a subset of circRNAs associated with cell transformation. We verified that the expression of circLMBR1 in bladder epithelial malignant transformed cells was decreased compared with control cells, as well as in BC tissues and bladder cell lines. Furthermore, circLMBR1 was seen to inhibit the proliferation, invasion, and migration of BC cells both in vitro and in vivo. Mechanistically, circLMBR1 was found to exert its antitumor effect by binding to the protein ALDH1A3.
UNASSIGNED: Our findings have revealed that circLMBR1 inhibits the progression of BC cells by binding to ALDH1A3 and upregulating its expression. As such, circLMBR1 serves as a promising predictor of BC and may provide a novel therapeutic target for the treatment of BC.
摘要:
环状RNA(circRNAs)已被鉴定为在膀胱癌(BC)的发展中起着不可或缺的作用。然而,circRNAs在BC化学致癌作用中的作用机制尚不清楚.
为了探索这种机制,我们使用RNA高通量测序来鉴定膀胱上皮细胞和化学诱导的恶性转化BC细胞中差异表达的circRNA。随后,通过体外实验研究了circLMBR1在BC中的生物学功能和分子机制。最后,进行动物实验以检查circLMBR1在体内的临床相关性。
我们对化学致癌物诱导的细胞恶性转化过程中环状RNA表达的分析鉴定了与细胞转化相关的circRNAs子集。我们证实circLMBR1在膀胱上皮恶性转化细胞中的表达较对照细胞降低,以及BC组织和膀胱细胞系。此外,发现circLMBR1抑制增殖,入侵,和BC细胞在体外和体内的迁移。机械上,发现circLMBR1通过与蛋白质ALDH1A3结合而发挥其抗肿瘤作用。
我们的发现表明,circLMBR1通过与ALDH1A3结合并上调其表达来抑制BC细胞的进展。因此,circLMBR1作为BC的一个有前途的预测因子,可能为BC的治疗提供一个新的治疗靶点。
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