ABSTRACT

RNA-binding proteins are important regulators of RNA metabolism and are of critical importance in all steps of the gene expression cascade. The role of aberrantly expressed RBPs in human disease is an exciting research field and the potential application of RBPs as a therapeutic target or a diagnostic marker represents a fast-growing area of research.

Aberrant overexpression of the human RNA-binding protein La has been found in various cancer entities including lung, cervical, head and neck, and chronic myelogenous leukaemia. Cancer-associated La protein supports tumour-promoting processes such as proliferation, mobility, invasiveness and tumour growth. Moreover, the La protein maintains the survival of cancer cells by supporting an anti-apoptotic state that may cause resistance to chemotherapeutic therapy.

The human La protein represents a multifunctional post-translationally modified RNA-binding protein with RNA chaperone activity that promotes processing of non-coding precursor RNAs but also stimulates the translation of selective messenger RNAs encoding tumour-promoting and anti-apoptotic factors. In our model, La facilitates the expression of those factors and helps cancer cells to cope with cellular stress. In contrast to oncogenes, able to initiate tumorigenesis, we postulate that the aberrantly elevated expression of the human La protein contributes to the non-oncogenic addiction of cancer cells. In this review, we summarize the current understanding about the implications of the RNA-binding protein La in cancer progression and therapeutic resistance. The concept of exploiting the RBP La as a cancer drug target will be discussed.

摘要

RNA 结合蛋白是 RNA 代谢的重要调节剂，在基因表达级联的所有步骤中都至关重要。异常表达的 RBP 在人类疾病中的作用是一个令人兴奋的研究领域，RBP 作为治疗靶点或诊断标志物的潜在应用代表了一个快速增长的研究领域。

在各种癌症实体中发现了人类 RNA 结合蛋白 La 的异常过度表达，包括肺癌、宫颈癌、头颈癌和慢性粒细胞白血病。癌症相关的 La 蛋白支持肿瘤促进过程，如增殖、迁移、侵袭和肿瘤生长。此外，La 蛋白通过支持可能导致化疗耐药的抗凋亡状态来维持癌细胞的存活。

人类 La 蛋白是一种多功能的翻译后修饰的 RNA 结合蛋白，具有 RNA 伴侣活性，可促进非编码前体 RNA 的加工，但也刺激编码肿瘤促进和抗凋亡因子的选择性信使 RNA 的翻译。在我们的模型中，La 促进这些因子的表达并帮助癌细胞应对细胞压力。与能够启动肿瘤发生的致癌基因相反，我们假设人类 La 蛋白的异常升高表达有助于癌细胞的非致癌成瘾。在这篇综述中，我们总结了目前对 RNA 结合蛋白 La 在癌症进展和治疗抵抗中的影响的理解。将讨论利用 RBP La 作为癌症药物靶点的概念。