TY - JOUR
T1 - Therapeutic SHPRH-146aa encoded by circ-SHPRH dynamically upregulates P21 to inhibit CDKs in neuroblastoma
AU - Chang, Saishuo
AU - Ren, Dong
AU - Zhang, Li
AU - Liu, Shan
AU - Yang, Wei
AU - Cheng, Haiyan
AU - Zhang, Xuexi
AU - Hong, Enyu
AU - Geng, Di
AU - Wang, Yadi
AU - Chen, Chenghao
AU - Zhang, Jie
AU - Shi, Tieliu
AU - Guo, Yongli
AU - Ni, Xin
AU - Wang, Huanmin
AU - Jin, Yaqiong
N1 - Publisher Copyright:
© 2024 Elsevier B.V.
PY - 2024/8/28
Y1 - 2024/8/28
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85198518810
U2 - 10.1016/j.canlet.2024.217120
DO - 10.1016/j.canlet.2024.217120
M3 - 文章
C2 - 39002691
AN - SCOPUS:85198518810
SN - 0304-3835
VL - 598
JO - Cancer Letters
JF - Cancer Letters
M1 - 217120
ER -
