Centre for Genetic Disorders, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
Centre for Genetic Disorders, Institute of Science, Banaras Hindu University, Varanasi 221005, India.
Biochim Biophys Acta Gen Subj. 2020 Dec;1864(12):129719. doi: 10.1016/j.bbagen.2020.129719. Epub 2020 Aug 31.
Renal Cell Carcinoma (RCC) is the ninth leading cause of death among kidney cancer. Xp11.2 translocation harboring TFE3 fusion proteins, act as an oncogene in translocation cancers that constitute the hallmark of translocation renal cell carcinoma (tRCC). G-quadruplex (G4), an alternative nucleic acid structure is an emerging and promising factor in cancer. The presence of G4 within the genome plays a pioneering role in cancer as it contributes to genomic aberration as well as inhibition in cell proliferation.
Here we discuss the link between G4 and tRCC. We compile the available information of G-quadruplex & propose their dual role in tRCC, suggesting both stabilization and destabilization of G-quadruplex could be considered targets for tRCC.
Our in Silico analysis of TFE3 and their three fusions partner's PRCC, SFPQ, and ASPSCR1 discloses a few putative G4 forming sequences (PQS) in their corresponding fusion gene or fusion transcript. Stabilization of G4 structure within fusion gene/transcript can be of great use towards potential therapeutics targeting fusion protein derived oncogenesis, as G4 is a serious menace for DNA polymerization, transcription & translation. G-quadruplex at intron-2 of the TFE3 has been reported to mediate its translocation also. Both stabilization and destabilization of the G4 structure would be a promising approach in the suppression of cancerous cell proliferation.
Pioneering studies discovered the relevance of G4 in cancer therapy and explore our approaches towards therapeutic innovation against oncogenic fusion protein and tRCC. Selectively targeting G4 in oncogenic fusion transcript will emerge as potential druggable structures.
肾细胞癌（RCC）是导致肾癌死亡的第九大原因。Xp11.2 易位携带 TFE3 融合蛋白，作为易位癌的癌基因，构成易位肾细胞癌（tRCC）的标志。G-四链体（G4）是一种替代核酸结构，是癌症中一个新兴且有前途的因素。基因组中 G4 的存在在癌症中起着开创性的作用，因为它有助于基因组异常以及抑制细胞增殖。
本文讨论了 G4 与 tRCC 之间的联系。我们整理了 G-四链体的现有信息，并提出了它们在 tRCC 中的双重作用，表明 G-四链体的稳定和不稳定都可以被认为是 tRCC 的靶点。
我们对 TFE3 及其三个融合伙伴 PRCC、SFPQ 和 ASPSCR1 的计算机分析揭示了它们相应融合基因或融合转录本中几个可能的 G4 形成序列（PQS）。融合基因/转录本中 G4 结构的稳定对于靶向融合蛋白衍生致癌作用的潜在治疗可能非常有用，因为 G4 对 DNA 聚合酶、转录和翻译是一个严重的威胁。TFE3 内含子 2 中的 G-四链体已被报道介导其易位。G4 结构的稳定和不稳定都是抑制癌细胞增殖的有前途的方法。
开创性的研究发现了 G4 在癌症治疗中的相关性，并探讨了我们针对致癌融合蛋白和 tRCC 的治疗创新方法。选择性靶向致癌融合转录本中的 G4 将成为潜在的可成药结构。
