School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, India.
J Cell Biochem. 2019 Sep;120(9):14700-14710. doi: 10.1002/jcb.28731. Epub 2019 May 14.
Oncogenesis involves continuous genetic alterations that lead to compromised cellular integrity and immortal cell fate. The cells remain under excessive stress due to endo- and exogenous influences. Human Satellite III long noncoding RNA (SatIII lncRNA) is a key regulator of the global cellular stress response, although its function is poorly explained in cancers. The principal regulator of cancer meshwork is tumor protein p53, which if altered may result in chemoresistance. The heat shock factor 1 (HSF1) being a common molecule between the oncogenic control and global cellular stress acts as an oncogene as well as transcribes SatIII upon heat shock. This prompted us to determine the structure of SatIII RNA and establish the association between SatIII-HSF1-p53. We determined the most stable structure of SatIII RNA with the least energy of - 115.7 kcal/mol. Also, we observed a possible interaction of p53 with SatIII and HSF1 using support vector machine (SVM) algorithm for predicting RNA-protein interaction (RPI). Further, we employ the STRING database to understand if p53 is an interacting component of the nuclear stress bodies (nSBs). A precise inference was drawn from molecular docking which confirmed the interaction of SatIII-HSF1-p53, where a mutated p53 resulted in an altered DNA-binding property with the SatIII molecule. This study being first of its kind infers p53 to be a possible integral component of the nSBs, which may regulate cellular stress response during cancer progression in the presence of HSF1 and SatIII. An extended research on the regulations of SatIII and p53 may open new avenues in the field of apoptosis in cancer and the early approach of molecular targeting.
肿瘤发生涉及导致细胞完整性受损和细胞永生化的连续遗传改变。由于内源性和外源性影响，细胞仍然处于过度应激状态。人类卫星 III 长链非编码 RNA（SatIII lncRNA）是细胞整体应激反应的关键调节因子，尽管其在癌症中的功能尚未得到充分解释。癌症网络的主要调节因子是肿瘤蛋白 p53，如果发生改变，可能导致化疗耐药。热休克因子 1（HSF1）是致癌控制和细胞整体应激之间的共同分子，既作为癌基因，又在热休克时转录 SatIII。这促使我们确定 SatIII RNA 的结构，并建立 SatIII-HSF1-p53 之间的关联。我们确定了 SatIII RNA 的最稳定结构，其能量最低为-115.7 kcal/mol。此外，我们使用支持向量机（SVM）算法预测 RNA-蛋白质相互作用（RPI），观察到 p53 与 SatIII 和 HSF1 之间可能存在相互作用。此外，我们利用 STRING 数据库了解 p53 是否是核应激体（nSBs）的相互作用成分。分子对接得出了精确的推断，证实了 SatIII-HSF1-p53 的相互作用，其中突变型 p53导致与 SatIII 分子的 DNA 结合特性发生改变。这项研究是同类研究中的首例，推断 p53 可能是 nSBs 的一个组成部分，在 HSF1 和 SatIII 存在的情况下，可能调节癌症进展过程中的细胞应激反应。对 SatIII 和 p53 的调控进行深入研究，可能为癌症细胞凋亡和早期分子靶向治疗开辟新途径。
