Hsa_circ_0005379 通过 EGFR 通路调节口腔鳞状细胞癌的恶性行为。
Hsa_circ_0005379 regulates malignant behavior of oral squamous cell carcinoma through the EGFR pathway.
机构信息
Department of Oral and Maxillofacial Surgery, Peking University Shenzhen Hospital, No. 1120 Lianhua Road, Shenzhen, 518001, Guangdong, China.
Peking University Shenzhen Hospital Clinical College, Anhui Medical University, Hefei, Anhui, China.
出版信息
BMC Cancer. 2019 Apr 29;19(1):400. doi: 10.1186/s12885-019-5593-5.
BACKGROUND
Oral squamous cell carcinoma (OSCC) is an oral and maxillofacial malignancy with a high incidence worldwide. Accumulating evidence indicates that circular RNAs (circRNAs) play a vital role in modulating tumor development. However, the mechanism of circRNA action in human OSCC remains largely unknown.
METHODS
By using high-throughput transcriptome sequencing technology, we conducted a comprehensive study of circRNAs in human OSCC. The effect of circRNA hsa_circ_0005379 on OSCC tissues and cell lines was monitored by qRT-PCR, Transwell assay, flow cytometry, and western blot analysis. Xenograft mouse models were used to assess tumor growth and animal survival.
RESULTS
We found that circRNA hsa_circ_0005379 expression is significantly lower in OSCC tissue compared to paired non-cancerous matched tissue and is associated with tumor size and differentiation. Overexpression of hsa_circ_0005379 effectively inhibits migration, invasion, and proliferation of OSCC cells in vitro and suppresses OSCC growth in nude mice in vivo. Mechanistic studies revealed that hsa_circ_0005379 may be involved in the regulation of the epidermal growth factor receptor (EGFR) pathway. Furthermore, we found that high expression of hsa_circ_0005379 could significantly enhance the sensitivity of OSCC to the cetuximab drug.
CONCLUSIONS
Our findings provide evidence that hsa_circ_0005379 regulates OSCC malignancy and may be a new therapeutic target for OSCC treatment.
背景
口腔鳞状细胞癌（OSCC）是一种口腔和颌面恶性肿瘤，全球发病率较高。越来越多的证据表明，环状 RNA（circRNA）在调节肿瘤发展中起着至关重要的作用。然而，circRNA 在人类 OSCC 中的作用机制在很大程度上尚不清楚。
方法
通过使用高通量转录组测序技术，我们对人类 OSCC 中的 circRNA 进行了全面研究。通过 qRT-PCR、Transwell 测定、流式细胞术和 Western blot 分析监测 circRNA hsa_circ_0005379 对 OSCC 组织和细胞系的影响。使用异种移植小鼠模型评估肿瘤生长和动物存活情况。
结果
我们发现，与配对的非癌组织相比，OSCC 组织中 circRNA hsa_circ_0005379 的表达明显降低，并且与肿瘤大小和分化相关。hsa_circ_0005379 的过表达可有效抑制 OSCC 细胞在体外的迁移、侵袭和增殖，并抑制裸鼠体内的 OSCC 生长。机制研究表明，hsa_circ_0005379 可能参与调节表皮生长因子受体（EGFR）途径。此外，我们发现 hsa_circ_0005379 的高表达可显著提高 OSCC 对西妥昔单抗药物的敏感性。
结论
我们的研究结果表明，hsa_circ_0005379 调节 OSCC 恶性程度，可能是 OSCC 治疗的新治疗靶点。
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