长非编码 RNA HOXA-AS3 的肿瘤调节作用

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-04-07 DOI:10.1016/j.pbiomolbio.2024.04.003
Zhi Xiong Chong , Wan Yong Ho , Swee Keong Yeap
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引用次数: 0

摘要

长非编码 RNA(lncRNA)HOXA-AS3 的失调已被证明会导致多种癌症类型的发生。多项研究表明,这种长非编码 RNA 在多种癌症中具有肿瘤调节作用或预后意义。总的来说,HOXA-AS3 可作为一种竞争性内源性 RNA(ceRNA),抑制七种微 RNA(miRNA)的活性,包括 miR-29a-3p、miR-29 b-3p、miR-29c、miR-218-5p、miR-455-5p、miR-1286 和 miR-4319。这使这些 miRNA 的下游信使 RNA(mRNA)靶标摆脱了 miRNA 介导的翻译抑制,从而使它们能够发挥调节细胞活动的作用。受 lncRNA HOXA-AS3 及其相关下游靶标调控的途径包括 WNT/β-catenin 和上皮细胞向间质转化(EMT)活动。此外,HOXA-AS3 还能与同源染色体 HOXA3 和 HOXA6 等其他细胞蛋白相互作用,影响与这些蛋白相关的致癌信号通路。一般来说,HOXA-AS3 在大多数已讨论过的人类癌症中都有过表达,这使得该 lncRNA 成为诊断癌症或预测癌症患者临床结果的潜在候选者。因此,以HOXA-ASS3为靶点可能是一种减缓癌症进展的新治疗方法,也可能是一种潜在的生物标志物和治疗靶点。将 lncRNA HOXA-AS3 用作生物标志物或治疗靶点的一个缺点是,大多数报道 lncRNA HOXA-AS3 调节肿瘤作用的研究都是单一的观察性、体外或体内研究。要进一步证实lncRNA HOXA-AS3的肿瘤调节作用,必须进行更深入的机理研究和大规模临床试验。此外,目前还没有lncRNA HOXA-ASS3抑制剂经过临床前和临床试验,设计这样一种抑制剂至关重要,因为它有可能减缓癌症的进展。
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Tumour-regulatory role of long non-coding RNA HOXA-AS3

Dysregulation of long non-coding RNA (lncRNA) HOXA-AS3 has been shown to contribute to the development of multiple cancer types. Several studies have presented the tumour-modulatory role or prognostic significance of this lncRNA in various kinds of cancer. Overall, HOXA-AS3 can act as a competing endogenous RNA (ceRNA) that inhibits the activity of seven microRNAs (miRNAs), including miR-29a-3p, miR-29 b-3p, miR-29c, miR-218–5p, miR-455–5p, miR-1286, and miR-4319. This relieves the downstream messenger RNA (mRNA) targets of these miRNAs from miRNA-mediated translational repression, allowing them to exert their effect in regulating cellular activities. Examples of the pathways regulated by lncRNA HOXA-AS3 and its associated downstream targets include the WNT/β-catenin and epithelial-to-mesenchymal transition (EMT) activities. Besides, HOXA-AS3 can interact with other cellular proteins like homeobox HOXA3 and HOXA6, influencing the oncogenic signaling pathways associated with these proteins. Generally, HOXA-AS3 is overexpressed in most of the discussed human cancers, making this lncRNA a potential candidate to diagnose cancer or predict the clinical outcomes of cancer patients. Hence, targeting HOXA-AS3 could be a new therapeutic approach to slowing cancer progression or as a potential biomarker and therapeutic target. A drawback of using lncRNA HOXA-AS3 as a biomarker or therapeutic target is that most of the studies that have reported the tumour-regulatory roles of lncRNA HOXA-AS3 are single observational, in vitro, or in vivo studies. More in-depth mechanistic and large-scale clinical trials must be conducted to confirm the tumour-modulatory roles of lncRNA HOXA-AS3 further. Besides, no lncRNA HOXA-AS3 inhibitor has been tested preclinically and clinically, and designing such an inhibitor is crucial as it may potentially slow cancer progression.

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