Data from Subcellular Distribution of p53 by the p53-Responsive lncRNA <i>NBAT1</i> Determines Chemotherapeutic Response in Neuroblastoma

• DOI: 10.1158/0008-5472.c.6512115.v1
• Publication Date: 2023-03-31T05:57:19Z
• Authors: Sanhita Mitra; Somsundar Veppil ...; Mirco Di Marco; Prasanna Kumar Ju...; Subazini Thankasw...; Silke Reischl; Daniel Jachimowicz; Santhilal Subhash; Ivan Raimondi; Leo Kurian; Maite Huarte; Per Kogner; Matthias Fischer; John Inge Johnsen; Tanmoy Mondal; Chandrasekhar Kan...
• Keywords: Nuclear export signal

&lt;div&gt;Abstract&lt;p&gt;Neuroblastoma has a low mutation rate for the &lt;i&gt;p53&lt;/i&gt; gene. Alternative ways of p53 inactivation have been proposed in neuroblastoma, such as abnormal cytoplasmic accumulation wild-type p53. However, mechanisms leading to via are not well investigated. Here we show that neuroblastoma risk-associated locus 6p22.3-derived tumor suppressor &lt;i&gt;NBAT1&lt;/i&gt; is p53-responsive lncRNA regulates subcellular levels. Low expression provided resistance genotoxic drugs by promoting cytoplasm and loss from mitochondrial nuclear compartments. Depletion altered CRM1 function contributed p53-dependent gene during drug treatment. inhibition rescued functions sensitized &lt;i&gt;NBAT1&lt;/i&gt;-depleted cells drugs. Combined MDM2 was even more effective sensitizing aggressive with accumulation. Thus, our mechanistic studies uncover an &lt;i&gt;NBAT1&lt;/i&gt;-dependent CRM1/MDM2-based potential combination therapy patients high-risk neuroblastoma.&lt;/p&gt;Significance:&lt;p&gt;This study shows how mediates chemotherapeutic response modulating pathways identifies treatment strategy neuroblastoma.&lt;/p&gt;&lt;/div&gt;