Solovyeva Anna I, Afanasev Roman V, Popova Marina A, Enukashvily Natella I
Lab of the Non-Coding DNA Studies, Institute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, Russia.
Zoological Institute of Russian Academy of Sciences, 199034 St. Petersburg, Russia.
Curr Issues Mol Biol. 2024 Aug 5;46(8):8576-8599. doi: 10.3390/cimb46080505.
Transposable elements (TEs) comprise a substantial portion of the mammalian genome, with potential implications for both embryonic development and cancer. This study aimed to characterize the expression profiles of TEs in embryonic stem cells (ESCs), cancer cell lines, tumor tissues, and the tumor microenvironment (TME). We observed similarities in TE expression profiles between cancer cells and ESCs, suggesting potential parallels in regulatory mechanisms. Notably, four TE RNAs (HERVH, LTR7, HERV-Fc1, HERV-Fc2) exhibited significant downregulation across cancer cell lines and tumor tissues compared to ESCs, highlighting potential roles in pluripotency regulation. The strong up-regulation of the latter two TEs (HERV-Fc1, HERV-Fc2) in ESCs has not been previously demonstrated and may be a first indication of their role in the regulation of pluripotency. Conversely, tandemly repeated sequences (MSR1, CER, ALR) showed up-regulation in cancer contexts. Moreover, a difference in TE expression was observed between the TME and the tumor bulk transcriptome, with distinct dysregulated TE profiles. Some TME-specific TEs were absent in normal tissues, predominantly belonging to LTR and L1 retrotransposon families. These findings not only shed light on the regulatory roles of TEs in both embryonic development and cancer but also suggest novel targets for anti-cancer therapy. Understanding the interplay between cancer cells and the TME at the TE level may pave the way for further research into therapeutic interventions.
转座元件（TEs）构成了哺乳动物基因组的很大一部分，对胚胎发育和癌症都有潜在影响。本研究旨在表征TEs在胚胎干细胞（ESCs）、癌细胞系、肿瘤组织和肿瘤微环境（TME）中的表达谱。我们观察到癌细胞和ESCs之间TE表达谱的相似性，这表明调控机制可能存在潜在的相似之处。值得注意的是，与ESCs相比，四种TE RNA（HERVH、LTR7、HERV-Fc1、HERV-Fc2）在癌细胞系和肿瘤组织中均表现出显著下调，突出了它们在多能性调控中的潜在作用。后两种TE（HERV-Fc1、HERV-Fc2）在ESCs中的强烈上调此前尚未得到证实，这可能是它们在多能性调控中发挥作用的首个迹象。相反，串联重复序列（MSR1、CER、ALR）在癌症环境中表现出上调。此外，在TME和肿瘤整体转录组之间观察到TE表达的差异，TE谱存在明显的失调。一些TME特异性TE在正常组织中不存在，主要属于LTR和L1逆转录转座子家族。这些发现不仅揭示了TEs在胚胎发育和癌症中的调控作用，还为抗癌治疗提出了新的靶点。在TE水平上理解癌细胞与TME之间的相互作用可能为进一步研究治疗干预措施铺平道路。
