Targeting transposable elements in cancer: developments and opportunities

IF 9.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et biophysica acta. Reviews on cancer Pub Date : 2024-06-25 DOI:10.1016/j.bbcan.2024.189143
Zi-Yu Wang , Li-Ping Ge , Yang Ouyang , Xi Jin, Yi-Zhou Jiang
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Abstract

Transposable elements (TEs), comprising nearly 50% of the human genome, have transitioned from being perceived as “genomic junk” to key players in cancer progression. Contemporary research links TE regulatory disruptions with cancer development, underscoring their therapeutic potential. Advances in long-read sequencing, computational analytics, single-cell sequencing, proteomics, and CRISPR-Cas9 technologies have enriched our understanding of TEs' clinical implications, notably their impact on genome architecture, gene regulation, and evolutionary processes. In cancer, TEs, including long interspersed element-1 (LINE-1), Alus, and long terminal repeat (LTR) elements, demonstrate altered patterns, influencing both tumorigenic and tumor-suppressive mechanisms. TE-derived nucleic acids and tumor antigens play critical roles in tumor immunity, bridging innate and adaptive responses. Given their central role in oncology, TE-targeted therapies, particularly through reverse transcriptase inhibitors and epigenetic modulators, represent a novel avenue in cancer treatment. Combining these TE-focused strategies with existing chemotherapy or immunotherapy regimens could enhance efficacy and offer a new dimension in cancer treatment. This review delves into recent TE detection advancements, explores their multifaceted roles in tumorigenesis and immune regulation, discusses emerging diagnostic and therapeutic approaches centered on TEs, and anticipates future directions in cancer research.

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针对癌症中的转座元件:发展与机遇。
可转座元件(Transposable elements,TEs)占人类基因组的近 50%,已从被视为 "基因组垃圾 "转变为癌症进展的关键角色。当代研究将可转座元件调控紊乱与癌症发展联系起来,凸显了其治疗潜力。长读测序、计算分析、单细胞测序、蛋白质组学和 CRISPR-Cas9 技术的进步丰富了我们对 TEs 临床意义的理解,尤其是它们对基因组结构、基因调控和进化过程的影响。在癌症中,TE(包括 LINE-1、Alus 和 LTR)显示出改变的模式,对致瘤和抑瘤机制都有影响。TE 衍生的核酸和肿瘤抗原在肿瘤免疫中发挥着关键作用,是先天性和适应性反应的桥梁。鉴于 TE 在肿瘤学中的核心作用,TE 靶向疗法,特别是通过逆转录酶抑制剂和表观遗传调节剂,代表了癌症治疗的新途径。将这些以 TE 为重点的策略与现有的化疗或免疫治疗方案相结合,可以提高疗效,为癌症治疗提供一个新的维度。本综述深入探讨了 TE 检测的最新进展,探讨了 TE 在肿瘤发生和免疫调节中的多方面作用,讨论了以 TE 为中心的新兴诊断和治疗方法,并展望了癌症研究的未来方向。
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来源期刊
Biochimica et biophysica acta. Reviews on cancer
Biochimica et biophysica acta. Reviews on cancer 医学-生化与分子生物学
CiteScore
17.20
自引率
0.00%
发文量
138
审稿时长
33 days
期刊介绍: Biochimica et Biophysica Acta (BBA) - Reviews on Cancer encompasses the entirety of cancer biology and biochemistry, emphasizing oncogenes and tumor suppressor genes, growth-related cell cycle control signaling, carcinogenesis mechanisms, cell transformation, immunologic control mechanisms, genetics of human (mammalian) cancer, control of cell proliferation, genetic and molecular control of organismic development, rational anti-tumor drug design. It publishes mini-reviews and full reviews.
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