Department of Hepatobiliary Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.
Department of Pharmacology and Toxicology, Wright State University, Fairborn, OH, 45435, USA.
Biochem Biophys Res Commun. 2019 Jun 4;513(3):669-674. doi: 10.1016/j.bbrc.2019.04.012. Epub 2019 Apr 11.
Long noncoding RNAs (lncRNAs) are involved in tumorigenesis. Previously, lncRNA MNX1-AS1 was reported to increase the malignancy of ovarian cancer, cervical cancer and lung cancer. However, the potential function of MNX1-AS1 in hepatocellular carcinoma (HCC) remains unclear. In this study, we found that MNX1-AS1 was remarkably upregulated in HCC tissues and cell lines. Furthermore, MNX1-AS1 overexpression was related to advanced stage and metastasis, and predicted poor prognosis. Loss-of-function assays showed that MNX1-AS1 knockdown suppressed the proliferation, migration and invasion of HCC cells in vitro. Further investigation indicated that MNX1-AS1 silencing delayed HCC growth in vivo. Mechanistically, we identified that MNX1-AS1 was a competing endogenous RNA (ceRNA) for miR-218-5p. We demonstrated that MNX1-AS1 promoted COMMD8 expression through sponging miR-218-5p, and then contributed to HCC progression. Restoration of COMMD8 significantly reversed the effects of MNX1-AS1 knockdown. Taken together, our findings demonstrated that MNX1-AS1 promoted the malignant properties of HCC through targeting miR-218-5p/COMMD8 pathway.
长链非编码 RNA（lncRNAs）参与肿瘤发生。先前有研究报道，lncRNA MNX1-AS1 可增加卵巢癌、宫颈癌和肺癌的恶性程度。然而，MNX1-AS1 在肝细胞癌（HCC）中的潜在功能尚不清楚。在本研究中，我们发现 MNX1-AS1 在 HCC 组织和细胞系中显著上调。此外，MNX1-AS1 的过表达与晚期和转移有关，并预测预后不良。功能丧失实验表明，MNX1-AS1 敲低抑制 HCC 细胞在体外的增殖、迁移和侵袭。进一步的研究表明，MNX1-AS1 沉默延迟了 HCC 在体内的生长。机制上，我们鉴定出 MNX1-AS1 是 miR-218-5p 的竞争性内源性 RNA（ceRNA）。我们证明，MNX1-AS1 通过海绵吸附 miR-218-5p 促进 COMMD8 的表达，进而促进 HCC 进展。COMMD8 的恢复显著逆转了 MNX1-AS1 敲低的作用。综上所述，我们的研究结果表明，MNX1-AS1 通过靶向 miR-218-5p/COMMD8 通路促进 HCC 的恶性特性。
