Samantarrai Devyani, Mallick Bibekanand
RNAi and Functional Genomics Laboratory, Department of Life Science, National Institute of Technology Rourkela, Odisha 769008, India.
RNAi and Functional Genomics Laboratory, Department of Life Science, National Institute of Technology Rourkela, Odisha 769008, India.
Exp Cell Res. 2017 Aug 1;357(1):33-39. doi: 10.1016/j.yexcr.2017.04.017. Epub 2017 Apr 19.
Soft tissue sarcomas (STS) are a heterogeneous group of rare tumors with high metastatic potential. There being only a handful of publication on metastasis of STS, we investigated the miRNA mediated target gene regulations in modulating the metastatic processes in this cancer. In this study, we amalgamated gene and miRNA expression profiles of high-grade STS samples with miRNA target predictions and identified miR-429 targeting KIAA0101 as a novel pair, which remain unexplored in STS metastasis. We validated their expression in metastatic fibrosarcoma cell line, HT1080 and performed several functional assays using miRNA mimics and KIAA0101 over-expression vector to confirm their role in metastasis. We observed miR-429 is downregulated in HT1080 cells and acting as an anti-metastatic miRNA that inhibited proliferation, migration, anchorage independent growth and invasion by de-repressing KIAA0101. Moreover, the renilla luciferase reporter assay confirmed that miR-429 targets KIAA0101 by binding to its 3UTR and influence its expression. Taken together, our work demonstrated miR-429 mediates deregulation of KIAA0101 by acting as an anti-metastatic miRNA that targets KIAA0101 pro-metastatic gene during metastasis of STS.
软组织肉瘤(STS)是一组异质性的罕见肿瘤,具有高转移潜能。由于关于STS转移的出版物很少,我们研究了miRNA介导的靶基因调控在调节这种癌症转移过程中的作用。在本研究中,我们将高级别STS样本的基因和miRNA表达谱与miRNA靶标预测相结合,鉴定出miR-429靶向KIAA0101是一对新的组合,在STS转移中尚未被探索。我们在转移性纤维肉瘤细胞系HT1080中验证了它们的表达,并使用miRNA模拟物和KIAA0101过表达载体进行了多项功能试验,以证实它们在转移中的作用。我们观察到miR-429在HT1080细胞中表达下调,作为一种抗转移miRNA,通过去抑制KIAA0101来抑制增殖、迁移、非锚定依赖性生长和侵袭。此外,海肾荧光素酶报告基因试验证实miR-429通过与其3UTR结合靶向KIAA0101并影响其表达。综上所述,我们的工作表明miR-429作为一种抗转移miRNA,在STS转移过程中靶向KIAA0101促转移基因,介导KIAA0101的失调。