环状 RNA(circRNA) 是一类广泛存在的内源性非编码 RNA，其在生物过程中发挥着重要作用。环状 RNA 可以通过与 microRNA（miRNA）相互作用来调节基因表达，从而影响细胞的增殖、分化和凋亡等过程。 在本研究中，我们发现环状 RNA ciRS-7 在甲状腺癌组织和细胞中高表达。通过过表达和敲低实验，我们发现 ciRS-7 可以促进甲状腺癌细胞的增殖和迁移。机制研究表明，ciRS-7 通过与 miR-7 结合，从而抑制 miR-7 的表达。进一步研究发现，miR-7 可以靶向抑制表皮生长因子受体（EGFR）的表达。因此，ciRS-7 通过负调控 miR-7/EGFR 轴促进甲状腺癌细胞的增殖和迁移。 综上所述，我们的研究结果表明，ciRS-7 可能成为甲状腺癌治疗的一个潜在靶点。
ciRS-7 Promotes the Proliferation and Migration of Papillary Thyroid Cancer by Negatively Regulating the miR-7/Epidermal Growth Factor Receptor Axis.
机构信息
Department of Pathology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jian She Dong Avenue, Zhengzhou, China.
Henan Key Laboratory of Tumor Pathology, No. 1 Jian She Dong Avenue, Zhengzhou, China.
出版信息
Biomed Res Int. 2020 Jun 21;2020:9875636. doi: 10.1155/2020/9875636. eCollection 2020.
PURPOSE
The incidence of papillary thyroid cancer (PTC) is increasing, and traditional diagnostic methods are unsatisfactory. Therefore, identifying novel prognostic markers is very important. ciRS-7 has been found to play an important role in many cancers, but its role in PTC has not been reported. This study was performed to evaluate the biological role and mechanism of ciRS-7 in PTC. . The expression of ciRS-7 in PTC tissues and the matched adjacent tissues was determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The PTC cell lines (TPC-1 and BCPAP) were used to evaluate the role of ciRS-7. ciRS-7-siRNA and overexpression plasmid were constructed and transfected into PTC cells. A CCK-8 assay and colony formation assay were performed to explore the effects of ciRS-7 on cell proliferation. Annexin V/PI staining and FACS detection were used to detect cell apoptosis. Wound healing assay was performed to detect cell migration. A transwell assay was conducted to explore the effects of ciRS-7 on invasion and migration. Western blotting was performed to evaluate protein expression. The luciferase reporter system was used to determine the underlying mechanism of miR-7.
RESULT
ciRS-7 was highly expressed in PTC tissues and cell lines compared with the corresponding controls. In vitro study showed that ciRS-7 silencing suppressed proliferation, migration, and invasion of TPC-1 and BCPAP. Mechanistically, the effects of ciRS-7 on invasion and migration may be related to epithelial-mesenchymal transition (EMT). ciRS-7 silencing could attenuate effects on PTC cells induced by miR-7 knockdown. Epidermal growth factor receptor (EGFR), which was demonstrated to be a target of miR-7, decreased significantly in ciRS-7-siRNA PTC cells. Overexpression of EGFR also attenuated effects of PTC cells induced by silencing ciRS-7.
CONCLUSION
ciRS-7 was significantly upregulated in PTC tissues, and it promoted the progression of PTC by regulating the miR-7/EGFR axis. ciRS-7 is a promising prognostic biomarker and therapeutic target in PTC.
目的
甲状腺乳头状癌（PTC）的发病率正在增加，传统的诊断方法并不令人满意。因此，鉴定新的预后标志物非常重要。ciRS-7 已被发现在许多癌症中发挥重要作用，但它在 PTC 中的作用尚未报道。本研究旨在评估 ciRS-7 在 PTC 中的生物学作用和机制。通过定量逆转录聚合酶链反应（qRT-PCR）检测 PTC 组织及配对的相邻组织中的 ciRS-7 表达。使用 PTC 细胞系（TPC-1 和 BCPAP）评估 ciRS-7 的作用。构建 ciRS-7-siRNA 和过表达质粒，并转染至 PTC 细胞中。通过 CCK-8 检测和集落形成实验来研究 ciRS-7 对细胞增殖的影响。通过 Annexin V/PI 染色和 FACS 检测来检测细胞凋亡。通过划痕愈合实验来检测细胞迁移。通过 Transwell 实验来研究 ciRS-7 对侵袭和迁移的影响。通过 Western blot 来评估蛋白表达。使用荧光素酶报告系统来确定 miR-7 的潜在机制。
结果
与相应的对照相比，ciRS-7 在 PTC 组织和细胞系中高表达。体外研究表明，ciRS-7 沉默抑制 TPC-1 和 BCPAP 的增殖、迁移和侵袭。机制上，ciRS-7 对侵袭和迁移的影响可能与上皮-间充质转化（EMT）有关。ciRS-7 沉默可减弱 miR-7 敲低对 PTC 细胞的影响。表皮生长因子受体（EGFR）是 miR-7 的靶点，在 ciRS-7-siRNA PTC 细胞中显著降低。EGFR 的过表达也减弱了沉默 ciRS-7 对 PTC 细胞的影响。
结论
ciRS-7 在 PTC 组织中显著上调，通过调节 miR-7/EGFR 轴促进 PTC 的进展。ciRS-7 是 PTC 有前途的预后生物标志物和治疗靶点。
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