2. Academic Validation
  3. Activation of the p53 signaling pathway by piRNA-MW557525 overexpression induces a G0/G1 phase arrest thus inhibiting neuroblastoma growth

Activation of the p53 signaling pathway by piRNA-MW557525 overexpression induces a G0/G1 phase arrest thus inhibiting neuroblastoma growth

  • Eur J Med Res. 2023 Nov 8;28(1):503. doi: 10.1186/s40001-023-01493-w.
Tao Mi 1,  Xiaojun Tan 1 2,  Zhang Wang 1,  Zhaoxia Zhang 1,  Liming Jin,  Jinkui Wang 1,  Mujie Li 1,  Xin Wu 1,  Dawei He 3
Affiliations

Affiliations

  • 1 Department of Urology; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation Base of Child Development and Critical Disorders; Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Yuzhong District, Chongqing, 400014, People's Republic of China.
  • 2 Department of Urology, Nanchong Central Hospital, The Second Clinical Medical College, North Sichuan Medical College, Nanchong, 637000, Sichuan, China.
  • 3 Department of Urology; Chongqing Key Laboratory of Children Urogenital Development and Tissue Engineering; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation Base of Child Development and Critical Disorders; Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Yuzhong District, Chongqing, 400014, People's Republic of China. [email protected].
PMID: 37941038 DOI: 10.1186/s40001-023-01493-w
Abstract

Background: Neuroblastoma (NB) is the most common extracranial malignant solid tumor in children. Due to drug resistance to radiotherapy and chemotherapy, mainly due to the existence of Cancer Stem Cells (CSCs), some children still have a poor prognosis. Therefore, researchers have focused their attention on CSCs. Our research group successfully constructed Cancer stem cell-like cells named Piwil2-iCSCs by reprogramming human preputial fibroblasts (FBs) with the PIWIL2 gene in the early stage, and Piwil2-iCSCs were confirmed to induce the formation of embryonic tumors. PiRNAs, noncoding small RNAs that interact with PIWI proteins, play important roles in a variety of tumors. Therefore, our study aimed to explore the role of differentially expressed (DE) piRNAs derived from sequencing of Piwil2-iCSCs in NB.

Methods: The DE piRNAs in Piwil2-iCSCs were screened using high-throughput sequencing and further verified in NB tissues and cells. An unknown piRNA, named piRNA-MW557525, showed obvious downregulation in NB. Thus we studied the effect of piRNA-MW557525 on the biological behavior of NB through in vitro and in vivo experiments. On this basis, we successfully constructed a stably transfected NB cell line overexpressing piRNA-MW557525 and performed transcriptome sequencing to further explore the mechanism of piRNA-MW557525 in NB.

Results: In vitro, piRNA-MW557525 inhibited NB cell proliferation, migration and invasion and induced apoptosis; in vivo, piRNA-MW557525 significantly reduced the volume and weight of tumors and inhibited their proliferation, migration and invasion. piRNA-MW557525 overexpression induced G0/G1 phase arrest in NB cells via activation of the P53-P21-CDK2-Cyclin E signaling pathway thus inhibiting NB growth.

Conclusions: Our findings show that piRNA-MW557525 functions as a tumor suppressor gene in NB and may serve as an innovative biomarker and possible therapeutic target for NB.

Keywords

Cell cycle; Neuroblastoma; P53; piRNA-MW557525; piRNAs.

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