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揭示 HOXA11-AS 在人类癌症和其他疾病中的分子机制和功能的最新进展(综述)。

Recent advances in unraveling the molecular mechanisms and functions of HOXA11‑AS in human cancers and other diseases (Review).

机构信息

Tianjin Neurological Institute, Key Laboratory of Post‑Neuroinjury Neuro‑Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, Heping, Tianjin 300052, P.R. China.

Tianjin Customs District China, Heping, Tianjin 300041, P.R. China.

出版信息

Oncol Rep. 2020 Jun;43(6):1737-1754. doi: 10.3892/or.2020.7552. Epub 2020 Mar 19.

Abstract

A large number of previously published research articles have demonstrated that the expression levels of long noncoding RNAs (lncRNAs) are generally dysregulated, either through overexpression or underexpression, in cancer and other types of disease. As a recently discovered lncRNA, HOXA11 antisense RNA (HOXA11‑AS) is able to serve as an oncogenic or tumor‑suppressor gene and serves a vital role in the processes of proliferation, invasion, and migration of cancer cells. HOXA11‑AS appears to be a major factor contributing to epigenetic modification, and exerts transcriptional, post‑transcriptional, translational and post‑translational regulatory effects on genes through a variety of mechanisms; for example, by competing endogenous RNA (ceRNA) and a molecular scaffold mechanism. A number of reports have demonstrated that HOXA11‑AS functions as a protein scaffold for polycomb repressive complex 2 (PRC2), lysine‑specific histone demethylase 1 (LSD1) and DNA methyltransferase 1 (DNMT1) to perform epigenetic modifications on chromosomes in the nucleus. Furthermore, HOXA11‑AS is also located in the cytoplasm and can act as a ceRNA, which sponges miRNAs. In addition, HOXA11‑AS may be useful as a biomarker for the diagnosis and prognosis of cancer. In the present review article, the clinical value, phenotype and mechanism of HOXA11‑AS in a variety of tumors types are briefly summarized, as well as its clinical value in certain additional diseases. The perspective of the authors is that HOXA11‑AS may represent an effective tumor marker and therapeutic target for cancer diagnosis and therapy.

摘要

大量已发表的研究文章表明,长链非编码 RNA(lncRNA)的表达水平通常在癌症和其他类型的疾病中失调,表现为过表达或低表达。HOXA11 反义 RNA(HOXA11-AS)作为一种新发现的 lncRNA,能够作为癌基因或肿瘤抑制基因发挥作用,在癌细胞的增殖、侵袭和迁移过程中发挥重要作用。HOXA11-AS 似乎是表观遗传修饰的主要因素,通过多种机制对基因发挥转录、转录后、翻译和翻译后调控作用;例如,通过竞争性内源性 RNA(ceRNA)和分子支架机制。有报道表明,HOXA11-AS 作为多梳抑制复合物 2(PRC2)、赖氨酸特异性组蛋白去甲基酶 1(LSD1)和 DNA 甲基转移酶 1(DNMT1)的蛋白质支架,在核内对染色体进行表观遗传修饰。此外,HOXA11-AS 也位于细胞质中,可以作为 ceRNA,与 microRNA 结合。此外,HOXA11-AS 可能可作为癌症诊断和预后的生物标志物。在本综述文章中,简要总结了 HOXA11-AS 在多种肿瘤类型中的临床价值、表型和作用机制,以及其在某些其他疾病中的临床价值。作者认为 HOXA11-AS 可能代表癌症诊断和治疗的有效肿瘤标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3158/7160552/0b9f55e773b2/OR-43-06-1737-g00.jpg

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