MicroRNA-124a inhibits cell proliferation and migration in liver cancer by regulating interleukin-11

MicroRNA-124a 通过调节白细胞介素-11 抑制肝癌细胞增殖和迁移

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作者:Liedao Yu, Shuo Wang, Xiangjin Lin, Yang Lu, Pengcheng Gu

Abstract

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.

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