Chai Jie, Guo Dawei, Ma Wanli, Han Dali, Dong Wei, Guo Hongliang, Zhang Yi
Department of General Surgery, Shandong University Affiliated Shandong Cancer Hospital and InstituteShandong Province, China.
Shandong Academy of Medical SciencesShandong Province, China.
Am J Cancer Res. 2018 Mar 1;8(3):538-550. eCollection 2018.
Long non-coding RNAs (lncRNAs) have been shown to participate in cancer progression. In the present study, we explored the potential roles of lncRNA-PVT1 in the development process of colorectal cancer (CRC) via miR-455. We found that PVT1 is up-regulated in human CRC tissues compared to adjacent normal tissues. A functional study showed that the silencing of PVT1 expression by siRNAs inhibited cell proliferation, migration and invasion, whereas the overexpression of PVT1 accelerated cell proliferation, migration and invasion . A mechanistic study indicated PVT1 regulated the growth of CRC tumors by acting as a competing endogenous RNAs (ceRNA) and negatively regulated miR-455. Furthermore, we discovered that RUNX2, a functional transcription factor in CRC, up-regulated PVT1 expression. Therefore, our study suggested that the RUNX2/PVT1/miR-455 regulatory axis plays an important role in CRC tumorigenesis and may be a therapeutic target for the treatment of CRC.
长链非编码RNA（lncRNAs）已被证明参与癌症进展。在本研究中，我们通过miR-455探索了lncRNA-PVT1在结直肠癌（CRC）发生发展过程中的潜在作用。我们发现，与相邻正常组织相比，PVT1在人类CRC组织中上调。功能研究表明，通过小干扰RNA（siRNAs）沉默PVT1表达可抑制细胞增殖、迁移和侵袭，而PVT1的过表达则加速细胞增殖、迁移和侵袭。机制研究表明，PVT1作为竞争性内源RNA（ceRNA）发挥作用，负向调节miR-455，从而调控CRC肿瘤的生长。此外，我们发现RUNX2（一种在CRC中具有功能的转录因子）上调PVT1表达。因此，我们的研究表明，RUNX2/PVT1/miR-455调控轴在CRC肿瘤发生中起重要作用，可能是CRC治疗的一个靶点。
