Background: Transactivation Response Element RNA-binding Protein (TRBP2) is a double-stranded RNA-binding protein widely known for its critical contribution to RNA interference (RNAi), a conserved mechanism of gene-expression regulation mediated through small non-coding RNA moieties (ncRNAs). Nevertheless, TRBP2 has also proved to be involved in other molecular pathways and biological processes, such as cell growth, organism development, spermatogenesis, and stress response. Mutations or aberrant expression of TRBP2 have been previously associated with diverse human pathologies, including Alzheimer’s disease, cardiomyopathy, and cancer, with TRBP2 playing an essential role(s) in proliferation, invasion, and metastasis of tumor cells. Methods: Hence, the present study aims to investigate, via employment of advanced flow cytometry, immunofluorescence, cell transgenesis and bioinformatics technologies, new, still elusive, functions and properties of TRBP2, particularly regarding its cell cycle-specific control during cancer cell division. Results: We have identified a novel, mitosis-dependent regulation of TRBP2 protein expression, as clearly evidenced by the lack of its immunofluorescence-facilitated detection during mitotic phases, in several human cancer cell lines of different tissue origin. Notably, the obtained TRBP2-downregulation patterns seem to derive from molecular mechanisms that act independently of oncogenic activities (e.g., malignancy grade), metastatic capacities (e.g., low versus high), and mutational signatures (e.g., p53−/−or p53ΔΥ126) of cancer cells. Conclusions: Taken together, we herein propose that TRBP2 serves as a novel cell cycle-dependent regulator, likely exerting mitosis-suppression functions, and, thus, its mitosis-specific downregulation can hold strong promise to be exploited for the efficient and successful prognosis, diagnosis, and (radio-/chemo-)therapy of diverse human malignancies, in the clinic.
背景：反式激活反应元件RNA结合蛋白（TRBP2）是一种双链RNA结合蛋白，因其在RNA干扰（RNAi）中的关键作用而广为人知。RNA干扰是一种通过小分子非编码RNA介导的基因表达调控保守机制。然而，TRBP2也被证实参与其他分子通路和生物过程，如细胞生长、个体发育、精子发生和应激反应。先前研究表明，TRBP2的突变或异常表达与多种人类疾病相关，包括阿尔茨海默病、心肌病和癌症，其中TRBP2在肿瘤细胞的增殖、侵袭和转移过程中发挥重要作用。方法：因此，本研究旨在通过运用先进的流式细胞术、免疫荧光、细胞转基因和生物信息学技术，探索TRBP2尚未明确的新功能与特性，特别是在癌细胞分裂过程中对细胞周期的特异性调控作用。结果：我们在多种不同组织来源的人类癌细胞系中发现，TRBP2蛋白表达存在一种新型的有丝分裂依赖性调控机制，其有丝分裂期免疫荧光检测缺失的现象明确证实了这一点。值得注意的是，所获得的TRBP2下调模式似乎源于独立于癌细胞致癌活性（如恶性程度）、转移能力（如低转移与高转移）和突变特征（如p53−/−或p53ΔΥ126）的分子机制。结论：综上所述，我们认为TRBP2作为一种新型细胞周期依赖性调控因子，可能发挥有丝分裂抑制功能，因此其有丝分裂特异性下调机制在临床上具有重要应用前景，有望为多种人类恶性肿瘤的有效预后、诊断及（放/化）疗提供新策略。
肿瘤(癌症)患者之家