Disease Molecular Biology and Epigenetics Laboratory, National Institute of Molecular Biology and Biotechnology, University of the Philippines Diliman, 1101, Quezon City, Philippines.
Sci Rep. 2021 Apr 27;11(1):9021. doi: 10.1038/s41598-021-88539-3.
Circular RNAs have emerged as functional regulatory molecules whose aberrant expression has been linked to diverse pathophysiological processes. Here, we report that circPVT1 interferes with let-7 binding to NRAS, confirming this axis as one route by which circPVT1 can instigate an oncogenic program in A549 lung cancer cells and HCT116 colorectal cancer cells. CircPVT1 knockdown significantly reduced NRAS levels and attenuated cancer hallmark phenotypes such as proliferation, migration, resistance to apoptosis, cytoskeletal disorganization, and epithelial-mesenchymal transition. The effects of circPVT1 knockdown were at least partially rescued by blocking binding of let-7 to NRAS 3'UTR with a target protector, suggesting that a circPVT1/let-7/NRAS axis exists and acts in cells to reverse NRAS downregulation and favor oncogenicity. While the phenotypic effects of circPVT1 knockdown may be attributable to the global action of circPVT1, the target protection assays resolved the relative contribution of the circPVT1/let-7/NRAS axis specifically.
环状 RNA 已成为功能调节分子，其异常表达与多种病理生理过程有关。在这里，我们报告 circPVT1 干扰 let-7 与 NRAS 的结合，证实了这一轴作为 circPVT1 可以在 A549 肺癌细胞和 HCT116 结直肠癌细胞中引发致癌程序的途径之一。circPVT1 敲低显著降低了 NRAS 水平，并减弱了癌症标志性表型，如增殖、迁移、抗凋亡、细胞骨架紊乱和上皮-间充质转化。用靶标保护器阻断 let-7 与 NRAS 3'UTR 的结合，至少部分挽救了 circPVT1 敲低的作用，这表明 circPVT1/let-7/NRAS 轴存在并在细胞中起作用，以逆转 NRAS 下调并有利于致癌性。虽然 circPVT1 敲低的表型效应可能归因于 circPVT1 的全局作用，但靶标保护测定明确了 circPVT1/let-7/NRAS 轴的相对贡献。
