Long Noncoding RNA RC3H2 Facilitates Cell Proliferation and Invasion by Targeting MicroRNA-101-3p/EZH2 Axis in OSCC
Long Noncoding RNA RC3H2 Facilitates Cell Proliferation and Invasion by Targeting MicroRNA-101-3p/EZH2 Axis in OSCC
复制标题
长非编码 RNA RC3H2 通过靶向 OSCC 中的 MicroRNA-101-3p/EZH2 轴促进细胞增殖和侵袭
DOI：
10.1016/j.omtn.2020.02.006
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发表时间：
2020-06-05
影响因子：
8.8
通讯作者：
Cao, Wei
中科院分区：
文献类型：
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作者：
Wu, Kun;Jiang, Yingying;Cao, Wei
在我们以前的研究中，zeste增强子同源物2（EZH 2）已被证明是口腔鳞状细胞癌（OSCC）的关键致癌驱动因子。然而，EZH 2在OSCC中的调控机制仍然知之甚少。本文通过多转录组学、生物信息学分析和定量逆转录聚合酶链反应（qRT-PCR），筛选了长链非编码RNA RC 3 H2（RC 3 H2）、microRNA-101- 3 p（miR-101- 3 p）和EZH 2的共表达网络，并验证了其作为OSCC中竞争性内源性RNA（ceRNA）机制的可能性。RC 3 H2基因沉默抑制OSCC细胞增殖、集落形成、迁移和体外侵袭，并降低EZH 2和H3 K27 Me 3的表达，而RC 3 H2过表达显著促进OSCC细胞生长、集落形成、迁移、侵袭和体内异种移植肿瘤生长，并增加EZH 2和H3 K27 Me 3的表达。荧光原位杂交（FISH）检测证实，RC 3 H2主要定位于细胞质。RNApull-down和荧光素酶活性检测显示，miR-101- 3 p与RC 3 H2和EZH 2物理结合，其抑制剂可逆转RC 3 H2敲低对OSCC进展的抑制作用。综上所述，我们的研究结果表明，RC 3 H2作为完整的内源性RNA海绵miR-101- 3 p靶向EZH 2，并促进OSCC细胞的恶性行为。
In our previous studies, enhancer of zeste homolog 2 (EZH2) has been proven to be a key oncogenic driver in oral squamous cell carcinoma (OSCC). However, the regulatory mechanisms on EZH2 remain poorly understood in OSCC. Here, through multi-transcriptomics, bioinformatics analysis, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), the co-expression network of long noncoding RNA RC3H2 (RC3H2), microRNA-101-3p (miR-101-3p), and EZH2 were screened and validated as a competing endogenous RNA (ceRNA) mechanism in OSCC. Silencing of RC3H2 inhibited OSCC cell proliferation, colony formation, migration, and invasion in vitro and reduced the expression of EZH2 and H3K27Me3, whereas RC3H2 overexpression significantly promoted OSCC cell growth, colony formation, migration, invasion, and xenograft tumor growth in vivo and increased the expression of EZH2 and H3K27Me3. A fluorescence in situ hybridization (FISH) assay verified that RC3H2 was predominately localized to the cytoplasm. RNApull-down and luciferase activity assays showed that miR-101-3p was physically bound to RC3H2 as well as EZH2, and its inhibitor reversed the inhibitory effect of RC3H2 knockdown on progression of OSCC. Taken together, our findings demonstrate that RC3H2 as completive endogenous RNA sponging miR-101-3p targets EZH2 and facilitates OSCC cells' malignant behavior.