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人源环状RNA_101237:一种用于多发性骨髓瘤的新型诊断和预后生物标志物及潜在治疗靶点

hsa_circRNA_101237: A Novel Diagnostic and Prognostic Biomarker and Potential Therapeutic Target for Multiple Myeloma.

作者信息

Liu Xiao, Tang Hao, Liu Jing, Wang Xiang

机构信息

The Third Xiangya Hospital of Central South University, Changsha 410013, People's Republic of China.

Department of Hematology, First Affiliated Hospital of Anhui Medical University, Hefei 230022, People's Republic of China.

出版信息

Cancer Manag Res. 2020 Mar 20;12:2109-2118. doi: 10.2147/CMAR.S241089. eCollection 2020.

Abstract

BACKGROUND

It has been demonstrated that circular RNA (circRNA) plays a crucial role in the occurrence and development of tumors, but the diagnostic and predictive value of most circRNAs in tumor patients remains unclear, especially for multiple myeloma (MM).

METHODS

High-throughput circRNA microarray-based sequencing was used to identify the differentially expressed circRNAs in MM. qRT-PCR was then employed to detect hsa_circRNA_101237 expression levels in the bone marrow tissues from 143 MM patients (65 first-episode treatment-naive patients and 78 patients with recurrent/refractory disease), MM cells and bortezomib-resistant MM cell lines. Whether hsa_circRNA_101237 can be used as a potential biomarker and therapeutic target for MM was investigated.

RESULTS

The average expressions of hsa_circRNA_101237 in the bone marrow tissues from MM patients (especially those with recurrent/refractory disease), MM cells and bortezomib-resistant MM cell lines were increased significantly (P<0.01). hsa_circRNA_101237 was overexpressed in patients positive for 13q14 deletion, 1q21 amplification, P53 deletion, and t(4,14) and t(14,16). hsa_circRNA_101237 was closely related to prognosis of the patients, and its high expression was associated with shorter OS and PFS. In addition, those overexpressing hsa_circRNA_101237 were less responsive to bortezomib treatment. Bioinformatic analysis indicated that hsa_circRNA_101237 interacted with 11 miRNAs and 10 candidate mRNAs. This finding may shed new light on the subsequent studies on the working mechanism and functions.

CONCLUSION

It was first reported that hsa_circRNA_101237 was significantly upregulated in MM. It was indicated that hsa_circRNA_101237 may be a novel biomarker for MM, and it plays a significant role in the occurrence and development of MM.

摘要

背景

已有研究表明,环状RNA(circRNA)在肿瘤的发生发展中起关键作用,但大多数circRNA在肿瘤患者中的诊断和预测价值仍不明确,尤其是在多发性骨髓瘤(MM)中。

方法

采用基于高通量circRNA微阵列的测序技术来鉴定MM中差异表达的circRNA。随后,运用qRT-PCR检测143例MM患者(65例初治未接受过治疗的患者和78例复发/难治性疾病患者)骨髓组织、MM细胞以及硼替佐米耐药MM细胞系中hsa_circRNA_101237的表达水平。研究hsa_circRNA_101237是否可作为MM的潜在生物标志物和治疗靶点。

结果

hsa_circRNA_101237在MM患者(尤其是复发/难治性疾病患者)的骨髓组织、MM细胞以及硼替佐米耐药MM细胞系中的平均表达显著增加(P<0.01)。hsa_circRNA_101237在13q14缺失、1q21扩增、P53缺失以及t(4,14)和t(14,16)阳性的患者中过表达。hsa_circRNA_101237与患者预后密切相关,其高表达与较短的总生存期(OS)和无进展生存期(PFS)相关。此外,过表达hsa_circRNA_101237的患者对硼替佐米治疗的反应较差。生物信息学分析表明,hsa_circRNA_101237与11种microRNA和10种候选mRNA相互作用。这一发现可能为后续关于其作用机制和功能的研究提供新的线索。

结论

首次报道hsa_circRNA_101237在MM中显著上调。表明hsa_circRNA_101237可能是MM的一种新型生物标志物,并且在MM的发生发展中起重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68be/7094164/a74fa7141ef1/CMAR-12-2109-g0001.jpg

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