Department of Orthopedics Surgery, The First Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310006, P.R. China.
Mol Med Rep. 2018 Mar;17(3):3972-3978. doi: 10.3892/mmr.2017.8348. Epub 2017 Dec 27.
Liver cancer is the sixth most common malignant tumour and ranks in the top three cancers with regard to mortality due to metastasis and postsurgical recurrence. It is significant to understand the mechanisms underlying liver cancer for diagnosis and treatment. Cumulative evidence suggests that the abnormal regulation of microRNAs (miRNAs/miRs) may contribute to the development and metastasis of cancer. miR‑124a acts as a tumour suppressor in osteosarcoma, endometrial carcinoma, prostate cancer, and glioblastoma. However, the effects of miR‑124a in liver cancer and its biological mechanism are not fully understood. It has been demonstrated that miR‑124a is downregulated and interleukin (IL)‑11 is upregulated in the liver cancer tissues. In the present study, miR‑124a upregulation inhibited cell proliferation, migration and promoted cell apoptosis. Through a dual‑luciferase reporter assay, it was verified that IL‑11 is a direct target of miR‑124a. Furthermore, the overexpression of miR‑124a repressed the secretion of IL‑11 from hepatoma cells. Finally, it was identified that mimics of miR‑124a increased the expression of tissue inhibitor of matrix metalloproteinase‑2 (TIMP‑2) and Caspase‑3 and decreased the expression levels of matrix metalloproteinase 2 (MMP2), MMP9, B‑cell lymphoma 2, signal transducer and activator of transcription 3 (STAT3), and phosphorylated‑STAT3. In conclusion, the results indicated that miR‑124a has an important role as a tumour suppressor gene by targeting IL‑11. These findings may provide novel insights for clinical treatments to prevent the development of liver cancer.
肝癌是第六大常见恶性肿瘤,也是导致转移和术后复发导致死亡率排名前三的癌症。了解肝癌的发病机制对于诊断和治疗具有重要意义。有累积证据表明,微小 RNA(miRNAs/miRs)的异常调节可能有助于癌症的发展和转移。miR-124a 在骨肉瘤、子宫内膜癌、前列腺癌和神经胶质瘤中作为肿瘤抑制因子发挥作用。然而,miR-124a 在肝癌中的作用及其生物学机制尚不完全清楚。已经证明,miR-124a 在肝癌组织中下调,白细胞介素(IL)-11 上调。在本研究中,miR-124a 的上调抑制了细胞增殖、迁移,并促进了细胞凋亡。通过双荧光素酶报告基因检测,验证了 IL-11 是 miR-124a 的直接靶标。此外,miR-124a 的过表达抑制了肝癌细胞中 IL-11 的分泌。最后,确定 miR-124a 的模拟物增加了组织金属蛋白酶抑制剂 2(TIMP-2)和 Caspase-3 的表达,并降低了基质金属蛋白酶 2(MMP2)、MMP9、B 细胞淋巴瘤 2、信号转导和转录激活因子 3(STAT3)和磷酸化-STAT3 的表达水平。总之,这些结果表明,miR-124a 通过靶向 IL-11 作为一种肿瘤抑制基因发挥重要作用。这些发现可能为预防肝癌发展的临床治疗提供新的见解。