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环状 RNA hsa_circ_0087302 通过 Wnt/β-catenin 信号通路影响骨肉瘤的进展。

Hsa_circ_0087302, a circular RNA, affects the progression of osteosarcoma via the Wnt/β-catenin signaling pathway.

机构信息

Oncology Hospital, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, China.

Department of Orthopedics, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, 524001, China.

出版信息

Int J Med Sci. 2022 Aug 1;19(9):1377-1387. doi: 10.7150/ijms.69501. eCollection 2022.

Abstract

Osteosarcoma is the most common malignant tumor in adolescent bone malignancies. It has the characteristics of a high metastasis rate, high mortality and poor prognosis. As a subclass of endogenous noncoding RNAs, circRNAs have been identified to be related to the occurrence, development and prognosis of different kinds of cancers, but the mechanism of their effect on osteosarcoma is not clear. In the present study, we identified a novel circRNA, hsa_circ_0087302, by RNA-seq, and we found that it was expressed at low levels in osteosarcoma. Using RT-PCR, we confirmed that the expression of hsa_circ_0087302 in osteosarcoma cells was lower than that in osteoblasts. Functional validation experiments revealed that hsa_circ_0087302 overexpression inhibited proliferation, cell cycle, migration, and invasion in osteosarcoma cells. Furthermore, Western blotting experiments demonstrated that hsa_circ_0087302 affected the expression of cell cycle- and Wnt/β-catenin signaling pathway-related proteins. For the first time, we identified that hsa_circ_0087302 may affect the malignant biological behavior of osteosarcoma cells through the Wnt/β-catenin signaling pathway. In summary, hsa_circ_0087302 may provide a new direction for the diagnosis and treatment of osteosarcoma.

摘要

骨肉瘤是青少年骨骼恶性肿瘤中最常见的恶性肿瘤。它具有转移率高、死亡率高、预后差的特点。作为内源性非编码 RNA 的一个子类,circRNAs 已被确定与不同类型癌症的发生、发展和预后有关,但它们对骨肉瘤的作用机制尚不清楚。在本研究中,我们通过 RNA-seq 鉴定了一种新型 circRNA,hsa_circ_0087302,并发现其在骨肉瘤中表达水平较低。通过 RT-PCR,我们证实 hsa_circ_0087302 在骨肉瘤细胞中的表达低于成骨细胞。功能验证实验表明 hsa_circ_0087302 的过表达抑制了骨肉瘤细胞的增殖、细胞周期、迁移和侵袭。此外,Western blotting 实验表明 hsa_circ_0087302 影响细胞周期和 Wnt/β-catenin 信号通路相关蛋白的表达。我们首次发现 hsa_circ_0087302 可能通过 Wnt/β-catenin 信号通路影响骨肉瘤细胞的恶性生物学行为。总之,hsa_circ_0087302 可能为骨肉瘤的诊断和治疗提供新的方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98ab/9413560/1f13d0c15f4d/ijmsv19p1377g001.jpg

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