Department of Neurosurgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, China.
Eur Rev Med Pharmacol Sci. 2020 Jan;24(2):758-765. doi: 10.26355/eurrev_202001_20056.
The aim of this study was to uncover the role of lncRNA HANR in the progression of glioma and the underlying mechanism.
HANR expression level in 36 matched glioma tissues and adjacent non-tumoral tissues was determined by qRT-PCR. The relationship between HANR expression and pathological indexes of the glioma patients was analyzed. The Kaplan-Meier method was introduced to investigate the survival of glioma patients. After the knockdown of HANR, the proliferative, migratory, and invasive changes of U251 and SHG44 cells were determined. Bioinformatics and Dual-Luciferase Reporter Gene Assay were applied to predict and verify the downstream target of HANR, respectively. Furthermore, the rescue experiments were conducted to clarify the role of HANR/miRNA-335 regulatory loop in the progression of glioma.
HANR was significantly upregulated in glioma tissues and cell lines. Glioma patients with a high expression level of HANR presented remarkably higher rates of lymphatic metastasis and distant metastasis, as well as worse prognosis. The silence of HANR remarkably attenuated the proliferative, migratory, and invasive capacities of U251 and SHG44 cells. MiRNA-335 was the direct target of HANR and was significantly downregulated in glioma tissues. Meanwhile, the miRNA-335 level was negatively regulated by HANR. In addition, the knockdown of miRNA-335 partially reversed the regulatory effects of HANR on cellular behaviors of glioma.
LncRNA HANR is upregulated in glioma, which is closely correlated with metastasis and poor prognosis of glioma patients. In addition, HANR aggravates the progression of glioma by negatively regulating miRNA-335.
本研究旨在揭示长链非编码 RNA HANR 在胶质瘤进展中的作用及其潜在机制。
采用 qRT-PCR 检测 36 对配对的胶质瘤组织和相邻非肿瘤组织中的 HANR 表达水平。分析 HANR 表达与胶质瘤患者病理指标的关系。采用 Kaplan-Meier 法分析胶质瘤患者的生存情况。敲低 HANR 后，检测 U251 和 SHG44 细胞的增殖、迁移和侵袭变化。应用生物信息学和双荧光素酶报告基因检测分别预测和验证 HANR 的下游靶基因。进一步进行挽救实验，阐明 HANR/miRNA-335 调控环路在胶质瘤进展中的作用。
HANR 在胶质瘤组织和细胞系中明显上调。HANR 高表达的胶质瘤患者淋巴结转移和远处转移率明显较高，预后较差。沉默 HANR 可显著减弱 U251 和 SHG44 细胞的增殖、迁移和侵袭能力。miRNA-335 是 HANR 的直接靶基因，在胶质瘤组织中明显下调。同时，HANR 负调控 miRNA-335 水平。此外，miRNA-335 的敲低部分逆转了 HANR 对胶质瘤细胞行为的调节作用。
长链非编码 RNA HANR 在胶质瘤中上调，与胶质瘤患者的转移和预后不良密切相关。此外，HANR 通过负调控 miRNA-335 加重胶质瘤的进展。
