Department of General Surgery, The First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710077, P.R. China.
Oncol Rep. 2018 Feb;39(2):731-738. doi: 10.3892/or.2017.6130. Epub 2017 Dec 4.
Accumulating evidence indicates that microRNAs (miRNAs) play important roles in tumorigenesis and metastasis. Recent research has shown that miR‑196b is implicated in metastasis by regulating the migration and invasion of cancer cells. However, the clinical significance of miR‑196b and its role as well as the underlying mechanisms in hepatocellular carcinoma (HCC) remain largely unknown. Here, we detected miR‑196b expression in HCC and matched non-tumor tissues with qRT‑PCR. We found that miR‑196b displayed higher expression in HCC patient tissues and cells. Clinical analysis revealed that high miR‑196 expression was correlated with venous infiltration, advanced TNM stage and poor prognosis. Functionally, we demonstrated that miR‑196b promoted the migration and invasion of HCC cells in vitro. Moreover, miR‑196b knockdown restrained pulmonary metastasis in vivo. Mechanistically, we confirmed that miR‑196b could directly bind to 3'UTR of forkhead box P2 (FOXP2) mRNA and repress its expression. miR‑196b and FOXP2 showed a negative correlation in HCC tissues. More importantly, upregulation of FOXP2 antagonized miR‑196b‑mediated migration and invasion in Hep3B cells. Furthermore, FOXP2 knockdown partially reversed the anti‑metastatic function of the miR‑196b inhibitor on HCCLM3 cells. Taken together, we demonstrated that miR‑196b may function as a prognostic biomarker and suppressed FOXP2 expression, subsequently leading to the metastasis of HCC. Our findings highlight a novel mechanism of miR‑196b in the progression of HCC and identify miR‑196b/FOXP2 axis as a promising target for HCC.
越来越多的证据表明，microRNAs（miRNAs）在肿瘤发生和转移中发挥着重要作用。最近的研究表明，miR-196b 通过调节癌细胞的迁移和侵袭参与转移。然而，miR-196b 的临床意义及其在肝细胞癌（HCC）中的作用和潜在机制仍知之甚少。在这里，我们通过 qRT-PCR 检测了 HCC 及匹配的非肿瘤组织中 miR-196b 的表达。我们发现 miR-196b 在 HCC 患者组织和细胞中表达较高。临床分析显示，高 miR-196 表达与静脉浸润、晚期 TNM 分期和预后不良相关。功能上，我们证明 miR-196b 促进了 HCC 细胞在体外的迁移和侵袭。此外，miR-196b 敲低抑制了体内的肺转移。机制上，我们证实 miR-196b 可以直接结合 forkhead box P2（FOXP2）mRNA 的 3'UTR 并抑制其表达。miR-196b 和 FOXP2 在 HCC 组织中呈负相关。更重要的是，FOXP2 的上调拮抗了 Hep3B 细胞中 miR-196b 介导的迁移和侵袭。此外，FOXP2 敲低部分逆转了 miR-196b 抑制剂对 HCCLM3 细胞的抗转移功能。总之，我们证明 miR-196b 可能作为一种预后生物标志物发挥作用，并抑制 FOXP2 的表达，进而导致 HCC 的转移。我们的研究结果强调了 miR-196b 在 HCC 进展中的新机制，并确定了 miR-196b/FOXP2 轴作为 HCC 的一个有前途的治疗靶点。
