Zhang W, Li J-Z, Tai Q-Y, Tang J-J, Huang Y-H, Gao S-B
Department of Oncology, the Third Affiliated Hospital of Qiqihar Medical College, Qiqihar, Heilongjaing, P.R. China.
Eur Rev Med Pharmacol Sci. 2020 Jun;24(12):6551-6560. doi: 10.26355/eurrev_202006_21639.
As a new LncRNA, anti-differentiated non-coding RNA (DANCR) plays an important role in tumorigenesis and development, and its molecular mechanism in osteosarcoma is unclear. In this study, by investigating osteosarcoma tissue and cells, we explored the molecular mechanism by which lncRNA DANCR regulates the occurrence and development of osteosarcoma by targeting the miR-149 / MSI2 axis.
In this study, osteosarcoma tissues and adjacent tissues in 109 patients were collected, and the relative expression of DANCR was detected by qPCR. The correlation between DANCR expression and clinical classification was statistically analyzed. In order to explore the potential molecular mechanism of DANCR related to tumor migration and invasion, an overexpression and silencing test was performed on the osteosarcoma cell line Saos-2, and then qPCR method was used to test the expression of miR149, and cell scratch test was used to detect invasion after DANCR silencing and miR149 overexpression. Transwell assay was used to detect the invasion after DANCR silencing and miR149 overexpression. Finally, Western blot was used to verify the expression of MSI2 protein after overexpression and silencing of miR-149.
DANCR was significantly up-regulated in both osteosarcoma tissue and cells. The high expression of DANCR was significantly positively correlated with tissue typing and advanced TNM stage. DANCR can significantly reduce the migration and invasion of osteosarcoma cells. miRNA overexpression significantly reduced osteosarcoma cell migration and invasion. When miR-149 was overexpressed, MSI2 protein expression was significantly down-regulated. When miR-149 was silenced, MSI2 protein was significantly up-regulated.
LncRNA DANCR plays an important regulatory role in the occurrence and development of osteosarcoma. It may be used as a potential target in the treatment of osteosarcoma in the future, by targeting the miR-149/MSI2 axis to regulate the occurrence and development of osteosarcoma.
作为一种新型长链非编码RNA，抗分化非编码RNA（DANCR）在肿瘤发生发展中起重要作用，其在骨肉瘤中的分子机制尚不清楚。本研究通过对骨肉瘤组织和细胞进行研究，探讨长链非编码RNA DANCR通过靶向miR-149/MSI2轴调控骨肉瘤发生发展的分子机制。
本研究收集了109例患者的骨肉瘤组织及癌旁组织，采用qPCR检测DANCR的相对表达量。对DANCR表达与临床分级的相关性进行统计学分析。为探究DANCR与肿瘤迁移和侵袭相关的潜在分子机制，对骨肉瘤细胞系Saos-2进行过表达和沉默实验，然后用qPCR法检测miR149的表达，用细胞划痕实验检测DANCR沉默和miR149过表达后的侵袭情况。采用Transwell实验检测DANCR沉默和miR149过表达后的侵袭情况。最后，用蛋白质免疫印迹法验证miR-149过表达和沉默后MSI2蛋白的表达。
DANCR在骨肉瘤组织和细胞中均显著上调。DANCR的高表达与组织类型和晚期TNM分期显著正相关。DANCR可显著降低骨肉瘤细胞的迁移和侵袭。miRNA过表达显著降低骨肉瘤细胞的迁移和侵袭。当miR-149过表达时，MSI2蛋白表达显著下调。当miR-149沉默时，MSI2蛋白显著上调。
长链非编码RNA DANCR在骨肉瘤的发生发展中起重要调控作用。未来它可能作为骨肉瘤治疗的潜在靶点，通过靶向miR-149/MSI2轴调控骨肉瘤的发生发展。
