{Reference Type}: Journal Article
{Title}: Therapeutic SHPRH-146aa encoded by circ-SHPRH dynamically upregulates P21 to inhibit CDKs in neuroblastoma.
{Author}: Chang S;Ren D;Zhang L;Liu S;Yang W;Cheng H;Zhang X;Hong E;Geng D;Wang Y;Chen C;Zhang J;Shi T;Guo Y;Ni X;Wang H;Jin Y;
{Journal}: Cancer Lett
{Volume}: 598
{Issue}: 0
{Year}: 2024 Aug 28
{Factor}: 9.756
{DOI}: 10.1016/j.canlet.2024.217120
{Abstract}: Recent research has underscored the significance of circular RNAs (circRNAs) in various cancers, including neuroblastoma (NB). Specifically, circ-SHPRH, a unique circRNA, has been revealed to inhibit tumor growth by sequestering miRNAs or producing the SHPRH-146aa protein. To explore circ-SHPRH's involvement in NB and its potential application in gene therapy, this study examined circ-SHPRH expression in 94 NB tissues and cell lines (SK-N-BE(2), SH-SY5Y) using real-time PCR and fluorescence in situ hybridization (FISH). Functional assays encompassing both overexpression and knockdown experiments in NB cell lines, as well as in vivo investigations, were conducted. RNA-seq analysis revealed a correlation between circ-SHPRH and the pathway of P21 (CDKN1A), a pivotal cell cycle regulator. Validation through PCR and other techniques confirmed that circ-SHPRH upregulated P21 expression. Furthermore, the regulatory role of circ-SHPRH in the P21-CDK pathway was corroborated through SHPRH-146aa expression analysis. Notably, adenovirus-mediated circ-SHPRH overexpression effectively curbed NB tumor growth in NSG mice, while combining circ-SHPRH with everolimus exhibited potential for NB treatment. This study elucidates the remarkable significance of circ-SHPRH in NB and its prospective utility in gene therapy, thereby paving the way for innovative therapeutic approaches.