长链非编码RNA通过海绵化轴促进骨肉瘤的增殖和迁移。
The long non-coding RNA promotes osteosarcoma proliferation and migration by sponging axis.
作者信息
Ding Xiaomin, Zhang Yawen, Liang Jinrong, Yin Junyi, Akbar Naveed, Miguel Verónica, Zhou Yan
机构信息
Department of Oncology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Department of Medical Oncology, Shanghai Tongji University Affiliated Tongji Hospital, Shanghai, China.
出版信息
Ann Transl Med. 2022 Aug;10(15):835. doi: 10.21037/atm-22-3602.
BACKGROUND
The long-noncoding RNA colorectal neoplasia differentially expressed () gene has been found to be upregulated in several solid tumors. Whether affects osteosarcoma (OS) and its underling mechanism remains unknown.
METHODS
Tumor tissues and corresponding normal tissues were collected from 45 patients with OS. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was applied to determine lncRNA level in the tissues. Participants were divided into a high group and a low group according to the median value of lncRNA expression detected by in situ hybridization (ISH). The differences between high and low expression of lncRNA in patients were compared clinically by chi-square test. Kaplan-Meier survival analysis was applied to analyze the relationship between lncRNA expression and patient survival. Subsequently, silencing or overexpression of lncRNA were performed in MG63 and 143B cell lines, qRT-PCR was applied to verify the expression of lncRNA , , and dual-luciferase reporter assay was used to evaluate the targeting relationship between , lncRNA , and Cell Counting Kit-8 (CCK8), wound-healing, and Transwell assays were used to analyze for cell proliferation, migration, and invasion, respectively, and western blot was used to detect expression in cells.
RESULTS
The expression of in OS tissues was higher than that in normal tissues. High lncRNA expression was significantly associated with clinical stage, lung metastasis, and poor prognosis in OS patients. Additionally, overexpression of lncRNA promoted proliferation and migration of OS cells. Bioinformatics analysis showed that lncRNA competitively inhibited through acting as a competitive endogenous RNA (ceRNA). It was also revealed that is a binding target gene of lncRNA and that is involved in this process as a downstream target gene of .
CONCLUSIONS
The lncRNA promotes the proliferation and migration of OS cells by regulating the pathway, and lncRNA can be a significant marker of OS prognosis.
背景
长链非编码RNA结直肠肿瘤差异表达（）基因已被发现在多种实体瘤中上调。是否影响骨肉瘤（OS）及其潜在机制仍不清楚。
方法
收集45例骨肉瘤患者的肿瘤组织及相应正常组织。应用定量逆转录聚合酶链反应（qRT-PCR）检测组织中lncRNA水平。根据原位杂交（ISH）检测的lncRNA表达中位数，将参与者分为高组和低组。采用卡方检验比较lncRNA高表达和低表达患者之间的临床差异。应用Kaplan-Meier生存分析lncRNA表达与患者生存的关系。随后，在MG63和143B细胞系中进行lncRNA的沉默或过表达，应用qRT-PCR验证lncRNA、、的表达，并采用双荧光素酶报告基因检测法评估、lncRNA和之间的靶向关系。分别采用细胞计数试剂盒-8（CCK8）、伤口愈合和Transwell实验分析细胞增殖、迁移和侵袭能力，并采用蛋白质免疫印迹法检测细胞中的表达。
结果
骨肉瘤组织中的表达高于正常组织。lncRNA高表达与骨肉瘤患者的临床分期、肺转移及预后不良显著相关。此外，lncRNA过表达促进骨肉瘤细胞的增殖和迁移。生物信息学分析表明，lncRNA作为竞争性内源性RNA（ceRNA）竞争性抑制。还发现是lncRNA的结合靶基因，并且作为的下游靶基因参与此过程。
结论
lncRNA通过调节通路促进骨肉瘤细胞的增殖和迁移，lncRNA可作为骨肉瘤预后的重要标志物。
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