长链非编码 RNA PCGEM1 通过调控 miR-539-5p/CDK6 轴促进胶质瘤的恶性行为。
LncRNA PCGEM1 contributes to malignant behaviors of glioma by regulating miR-539-5p/CDK6 axis.
机构信息
Department of Intensive Care Unit, Wenzhou Central Hospital, Wenzhou Medical University, Wenzhou 325000, China.
Neurosurger Department, Wenzhou Central Hospital, Wenzhou Medical University, Wenzhou 325000, China.
出版信息
Aging (Albany NY). 2021 Feb 11;13(4):5475-5484. doi: 10.18632/aging.202476.
BACKGROUND
Glioma, one of the most prevalent and aggressive cancers, is regulated by long noncoding RNAs (lncRNAs). This study aims to research the functional mechanism of lncRNA PCGEM1 involved in glioma progression.
METHODS
Expression levels of PCGEM1, miR-539-5p and CDK6 were analyzed by qRT-PCR in NHA, U251, U87, and LN229 cells or glioma tissues. shRNAs were used to knock down PCGEM1 in U251 and LN229 cells. Kaplan-Meier curve and log rank test were utilized to examine survival rate. CCK8 (Cell Counting Kit-8) assay, colony formation assay and EdU staining were conducted to detect cell proliferation. Transwell assay was performed to evaluate cell migration and invasion. Luciferase reporter assay was conducted to assess RNA interaction between PCGEM1 and miR-539-5p. Nude mice were used for tumor xenograft assay.
RESULTS
LncRNA PCGEM1 was upregulated in glioma tissues and tumor cell lines. PCGEM1 upregulation predicted unsatisfactory prognosis. PCGEM1 knockdown inhibited proliferation, colony formation, migration and invasion. PCGEM1 knockdown delayed tumor growth . PCGEM1 played as a competing endogenous RNA (ceRNA) for miR-539-5p to promote CDK6 expression. MiR-539-5p mimics repressed glioma progression while CDK6 overexpression reversed the roles of PCGEM1 knockdown.
CONCLUSION
PCGEM1 knockdown suppressed glioma progression through sponging miR-539-5p and regulating CDK6 expression, implying PCGEM1 as a potential therapeutic target.
背景
神经胶质瘤是最常见和侵袭性最强的癌症之一，受长链非编码 RNA（lncRNA）的调控。本研究旨在研究 lncRNA PCGEM1 在神经胶质瘤进展中所涉及的功能机制。
方法
通过 qRT-PCR 分析 NHA、U251、U87 和 LN229 细胞或神经胶质瘤组织中 PCGEM1、miR-539-5p 和 CDK6 的表达水平。使用 shRNA 敲低 U251 和 LN229 细胞中的 PCGEM1。通过 Kaplan-Meier 曲线和对数秩检验检测生存率。通过 CCK8（细胞计数试剂盒-8）检测、集落形成检测和 EdU 染色检测细胞增殖。通过 Transwell 检测评估细胞迁移和侵袭。通过荧光素酶报告检测评估 PCGEM1 与 miR-539-5p 之间的 RNA 相互作用。使用裸鼠进行肿瘤异种移植实验。
结果
lncRNA PCGEM1 在神经胶质瘤组织和肿瘤细胞系中上调。PCGEM1 上调预示着预后不佳。PCGEM1 敲低抑制增殖、集落形成、迁移和侵袭。PCGEM1 敲低延迟肿瘤生长。PCGEM1 作为 miR-539-5p 的竞争性内源性 RNA（ceRNA）促进 CDK6 表达。miR-539-5p 模拟物抑制神经胶质瘤进展，而 CDK6 过表达逆转了 PCGEM1 敲低的作用。
结论
PCGEM1 敲低通过海绵吸附 miR-539-5p 并调节 CDK6 表达来抑制神经胶质瘤的进展，表明 PCGEM1 可能是一个潜在的治疗靶点。
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