Knockdown of hsa_circ_0008922 inhibits the progression of glioma.
Knockdown of hsa_circ_0008922 inhibits the progression of glioma.
复制标题
hsa_circ_0008922 的敲低抑制神经胶质瘤的进展
作者：
Xue C;Liu C;Yun X;Zou X;Li X;Wang P;Li F;Ge Y;Zhang Q;Xie X;Li X;Luo B
神经胶质瘤是起源于中枢神经系统中的神经胶质细胞的肿瘤。虽然在诊断和治疗方面取得了显著进展，但大多数高级别胶质瘤患者容易复发。因此，分子靶向治疗有望成为胶质瘤辅助治疗的新方向。近年来，大量研究发现环状RNA（circRNA）在包括胶质瘤在内的多种肿瘤的发生、发展过程中起重要作用。我们前期的研究发现hsa_circ_0008922在胶质瘤组织中表达上调。circ_0008922在胶质瘤中的生物学机制尚未报道。因此，本研究对hsa_circ_0008922在胶质瘤中的表达进行了初步的研究，并探讨其生物学功能。采用实时荧光定量聚合酶链反应（qRT-PCR）检测hsa_circ_0008922在40例胶质瘤组织和4株胶质瘤细胞系（A172、U251、SF 763和U87）中的表达。Fisher精确检验分析hsa_circ_0008922表达与胶质瘤患者临床病理特征的相关性。为了了解hsa_circ_0008922在胶质瘤中的潜在功能，我们构建了针对hsa_circ_0008922的小干扰RNA（siRNA），以下调其在胶质瘤细胞系A172和U251中的表达。用这些hsa_circ_0008922下调的细胞，如下进行一系列测定。CCK-8法检测细胞增殖情况，创伤愈合法检测细胞迁移能力，transwell法检测细胞侵袭能力。平板克隆形成试验评价细胞集落形成能力。流式细胞术结合Western blot检测细胞凋亡状态及凋亡相关蛋白caspase 3、caspase 9的表达。最后，利用生物信息学方法预测了hsa_circ_0008922可能的生物学通路和潜在的miRNA靶点。我们发现hsa_circ_0008922在胶质瘤组织中的表达是正常组织的3.4倍。has_circ_0008922的表达与WHO肿瘤分级相关。下调hsa_circ_0008922的表达后，胶质瘤细胞的增殖、集落形成、迁移、侵袭等恶性生物学行为受到抑制。同时，它还能诱导胶质瘤细胞凋亡。生物信息学预测分析表明，hsa_circ_0008922可能通过充当多个miRNAs（hsa-let-7 e-5 p、hsa-miR-506- 5 p、hsa-let-7 b-5 p、hsa-let-7 c-5 p和hsa-let-7a-5 p）的分子海绵而参与肿瘤相关通路。最后，我们整合我们的观察，建立一个circRNA-miRNA-mRNA预测网络。
A glioma is a tumor originating from glial cells in the central nervous system. Although significant progress has been made in diagnosis and treatment, most high-grade glioma patients are prone to recurrence. Therefore, molecular targeted therapy may become a new direction for adjuvant therapy in glioma. In recent years, many studies have revealed that circular RNA (circRNA) may play an important role in the occurrence and development of many tumors including gliomas. Our previous study found that the expression of hsa_circ_0008922 was up-regulated in glioma tissues upon RNA sequencing. The biological mechanism of circ_0008922 is still unreported in gliomas. Therefore, in this study, we preliminarily outlined the expression of hsa_circ_0008922 in glioma and explored its biological functions. The expression of hsa_circ_0008922 in forty glioma tissues and four glioma cell lines (A172, U251, SF763 and U87) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between hsa_circ_0008922 expression and clinicopathological features of glioma patients was evaluated by Fisher’s exact test. To understand the potential function of hsa_circ_0008922 in glioma, we constructed small interfering RNA (siRNA) to hsa_circ_0008922 to downregulate its expression in glioma cell lines A172 and U251. With these hsa_circ_0008922 downregulated cells, a series of assays were carried out as follows. Cell proliferation was detected by CCK8 assay, migration and invasion were determined by wound healing assay and transwell assay, respectively. Colony formation ability was evaluated by plate clonogenic assay. Moreover, flow cytometry combined with Western blot was performed to analyze apoptosis status and the expression of apoptotic related proteins (caspase 3 and caspase 9). Finally, the possible biological pathways and potential miRNA targets of hsa_circ_0008922 were predicted by bioinformatics. We found that the expression of hsa_circ_0008922 in glioma tissues was 3.4 times higher than that in normal tissues. The expression of has_circ_0008922 was correlated with WHO tumor grade. After down-regulating the expression of hsa_circ_0008922, malignant biological behavior of glioma cells was inhibited, such as cell proliferation, colony formation, migration, and invasion. At the same time, it also induced apoptosis of glioma cells. Predicted analysis by bioinformatics demonstrated that hsa_circ_0008922 may be involved in tumor-related pathways by acting as a molecular sponge for multiple miRNAs (hsa-let-7e-5p, hsa-miR-506-5p, hsa-let-7b-5p, hsa-let-7c-5p and hsa-let-7a-5p). Finally, we integrated our observation to build a circRNA-miRNA-mRNA predictive network.
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