PiRNA hsa_pir_018849通过调节CCN5 mRNA的稳定性促进骨肉瘤细胞的增殖和侵袭。

PiRNA hsa_pir_018849 promotes the proliferation and invasion of osteosarcoma cells by regulating the stability of CCN5 mRNA.

作者信息

Huang Jiale, Yang Saishuai, Liu Peng, Jiang He, Cui Zhiming, Chen Jiajia

机构信息

Department of Spine Surgery, Affiliated Hospital 2 of Nantong University, No. 666, ShengLi Road, Chongchuan District, Nantong, Jiangsu, 226001, China.

Research Institute for Spine and Spinal Cord Disease of Nantong University, No. 666, ShengLi Road, Chongchuan District, Nantong, Jiangsu, 226001, China.

出版信息

J Orthop Surg Res. 2025 Aug 2;20(1):725. doi: 10.1186/s13018-025-06148-6.

DOI:10.1186/s13018-025-06148-6

PMID:40753411

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12317495/

Abstract

BACKGROUND

Osteosarcoma is a primary malignant bone tumor and that is predominantly found in adolescents and young adults, and it often occurs during periods of rapid bone growth. The precise specific etiology of osteosarcoma remains largely unknown. Piwi-interacting RNAs (piRNAs) are a class of small noncoding RNAs that are typically 24 to 31 nucleotides long, and they have potential therapeutic applications in diseases.

METHODS

Small RNA sequencing and qPCR were initially used to detect differentially expressed piRNAs in the MG63 osteosarcoma cell line and in osteosarcoma tissues. The expression of hsa_piR_018849 in osteosarcoma cells was modulated using hsa_piR_018849 mimics and inhibitors. The impact of hsa_piR_018849 on the proliferation of osteosarcoma cells was assessed using CCK-8 and colony formation assays. Flow cytometry was used to investigate the effects of hsa_piR_018849 on osteosarcoma cell apoptosis. Cell scratch and Transwell assays were utilized to evaluate the impact of hsa_piR_018849 on the migration and invasion of osteosarcoma cells. mRNA sequencing was conducted to elucidate the mechanisms by which hsa_piR_018849 regulates osteosarcoma cell functions.

RESULTS

Overexpression of hsa_piR_018849 promoted the proliferation, migration, and invasion of osteosarcoma cells while inhibiting apoptosis. Conversely, knockdown of hsa_piR_018849 suppressed osteosarcoma cell proliferation, migration, and invasion but promoted osteosarcoma cell apoptosis. Hsa_piR_018849 facilitated the proliferation of osteosarcoma cells in vivo. The expression levels of CCN5 were reduced by hsa_piR_018849. Hsa_piR_018849 reduced the stability of CCN5 by binding to the coding sequence (CDS) region of CCN5 mRNA.

CONCLUSION

PiRNA hsa_piR_018849 regulates the function of osteosarcoma cells by targeting and inhibiting the expression of CCN5.

摘要

背景

骨肉瘤是一种原发性恶性骨肿瘤，主要发生在青少年和年轻成年人中，且常出现在骨骼快速生长时期。骨肉瘤的确切病因在很大程度上仍不清楚。Piwi相互作用RNA（piRNA）是一类小的非编码RNA，通常长度为24至31个核苷酸，它们在疾病中具有潜在的治疗应用。

方法

最初使用小RNA测序和qPCR来检测MG63骨肉瘤细胞系和骨肉瘤组织中差异表达的piRNA。使用hsa_piR_018849模拟物和抑制剂调节骨肉瘤细胞中hsa_piR_018849的表达。使用CCK-8和集落形成试验评估hsa_piR_018849对骨肉瘤细胞增殖的影响。流式细胞术用于研究hsa_piR_018849对骨肉瘤细胞凋亡的影响。利用细胞划痕和Transwell试验评估hsa_piR_018849对骨肉瘤细胞迁移和侵袭的影响。进行mRNA测序以阐明hsa_piR_018849调节骨肉瘤细胞功能的机制。

结果

hsa_piR_018849的过表达促进了骨肉瘤细胞的增殖、迁移和侵袭，同时抑制了细胞凋亡。相反，hsa_piR_018849的敲低抑制了骨肉瘤细胞的增殖、迁移和侵袭，但促进了骨肉瘤细胞凋亡。hsa_piR_018849促进了体内骨肉瘤细胞的增殖。hsa_piR_018849降低了CCN5的表达水平。hsa_piR_018849通过与CCN5 mRNA的编码序列（CDS）区域结合降低了CCN5的稳定性。