Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, PR China.
Biochem Biophys Res Commun. 2020 Apr 16;524(4):839-846. doi: 10.1016/j.bbrc.2020.01.055. Epub 2020 Feb 8.
Increasing evidences demonstrate that circular RNAs (circRNAs) are extensively implicated in various cancers including colorectal cancer (CRC). In the present study, we found that circRNA HIPK3 (circPIK3) was upregulated in CRC. We identified that circHIPK3 was closely related with unfavorable clinicopathological features in patients with CRC. Functional transwell assay and proliferation assay indicated that circHIPK3 served as an oncogene and promoted CRC cells migration, invasion and proliferation. Meanwhile, we found that formin like 2 (FMNL2) was a key downstream molecule in circHIPK3-induced metastasis and proliferation in CRC cells. We further verified that circHIPK3 was mainly located at cytoplasm through an immunofluorescence assay. An online bioinformatics screening and a GEO datasets analysis showed that microRNA 1207-5p (miR-1207-5p) was downregulated in CRC. Also, we found that miR-1207-5p shared a similar miR-1207-5p response elements (MREs-1207-5p). Meanwhile, we showed that miR-1207-5p suppressed CRC cells migration, invasion and proliferation via directly targeting of FMNL2. Even further, via a constructed luciferase assay, we indicated that circHIPK3 was another target of miR-1207-5p. Functionally, we proved that circHIPK3 enhanced FMNL2 mediated promotion of migration, invasion and proliferation by sponging of miR-1207-5p in CRC cells. In summary, the outcomes of this study illustrated that circHIPK3 promoted CRC cells migration, invasion and proliferation modulating of FMNL2 by sponging of miR-1207-5p. Our findings indicated that circHIPK3/miR-1207-5p/FMNL2 axis might be a new strategy in molecular treatment of CRC.
越来越多的证据表明,环状 RNA(circRNA)广泛参与包括结直肠癌(CRC)在内的多种癌症。在本研究中,我们发现环状 RNA HIPK3(circPIK3)在 CRC 中上调。我们确定 circHIPK3 与 CRC 患者不良的临床病理特征密切相关。功能性 transwell 测定和增殖测定表明,circHIPK3 作为癌基因促进 CRC 细胞迁移、侵袭和增殖。同时,我们发现formin 样 2(FMNL2)是 circHIPK3 诱导 CRC 细胞转移和增殖的关键下游分子。我们进一步通过免疫荧光测定证实 circHIPK3 主要位于细胞质中。在线生物信息学筛选和 GEO 数据集分析表明,miR-1207-5p(miR-1207-5p)在 CRC 中下调。此外,我们发现 miR-1207-5p 具有相似的 miR-1207-5p 反应元件(MREs-1207-5p)。同时,我们表明 miR-1207-5p 通过直接靶向 FMNL2 抑制 CRC 细胞迁移、侵袭和增殖。甚至进一步,通过构建荧光素酶测定,我们表明 circHIPK3 是 miR-1207-5p 的另一个靶点。功能上,我们证明 circHIPK3 通过海绵吸附 miR-1207-5p 增强了 FMNL2 介导的 CRC 细胞迁移、侵袭和增殖。总之,这项研究的结果表明,circHIPK3 通过海绵吸附 miR-1207-5p 促进了 FMNL2 介导的 CRC 细胞迁移、侵袭和增殖。我们的发现表明,circHIPK3/miR-1207-5p/FMNL2 轴可能是 CRC 分子治疗的新策略。