Upregulation of lncRNA HNF1A-AS1 promotes cell proliferation and metastasis in osteosarcoma through activation of the Wnt/β-catenin signaling pathway.

Upregulation of lncRNA HNF1A-AS1 promotes cell proliferation and metastasis in osteosarcoma through activation of the Wnt/β-catenin signaling pathway.
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DOI:
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发表时间:
2016-08
影响因子:
2.2
通讯作者:
Hongxing Zhao;Wengen Hou;Jingang Tao;Yilei Zhao;G. Wan;Chao Ma;Haibin Xu
Hongxing Zhao;Wengen Hou;Jingang Tao;Yilei Zhao;G. Wan;Chao Ma;Haibin Xu
中科院分区:
医学4区
文献类型:
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作者:
Hongxing Zhao;Wengen Hou;Jingang Tao;Yilei Zhao;G. Wan;Chao Ma;Haibin Xu

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HNF1A-反义1(HNF1A-AS1)是一种长的非编码RNA(LncRNA),与肺癌的转移有关,是肺癌的独立预后因素。最近的研究表明,HNF1A-AS1在癌变过程中起着重要的作用。然而,HNF1A-AS1在骨肉瘤(OS)进展中的确切作用和分子机制仍不清楚。在本研究中,我们发现HNF1A-AS1在OS组织中的表达明显高于其邻近的非肿瘤组织。HNF1A-AS1的表达水平与OS患者的临床分期、远处转移和总生存率降低呈正相关。此外,下调HNF1a-AS1的表达抑制了OS细胞的增殖和转移,并影响了OS细胞中Wnt/β-catenin通路的活性。WnT/β-连环蛋白途径激活剂可拮抗OS细胞中HNF1a-AS1基因的表达。综上所述,我们的研究表明HNF1a-As1通过调节Wnt/β-catenin通路的活性而促进OS的进展,提示HNF1a-As1可能是治疗OS的潜在靶点。
HNF1A-antisense 1 (HNF1A-AS1), a long non-coding RNA (lncRNA), is associated with metastasis and is an independent prognostic factor for lung cancer. Recent studies demonstrated that HNF1A-AS1 play important roles in cacinogenesis. However, the exact effects and molecular mechanisms of HNF1A-AS1 in osteosarcoma (OS) progression is still unclear. In the present study, we found that HNF1A-AS1 was markedly up-regulated in OS tissues compared to their adjacent non-tumor tissues. HNF1A-AS1 expression levels were positively associated with the clinical stage, distant metastasis, and reduced overall survival of OS patients. In addition, knockdown HNF1A-AS1 expression inhibited cell proliferation, metastasis and influences the activity of the Wnt/β-catenin pathway in OS cells. Wnt/β-catenin pathway activator (LiCl) rescued the anticancer effect of knockdown HNF1A-AS1 expression in OS cells. In conclusion, our study demonstrated that HNF1A-AS1 promoted the progression of OS via regulating the activity of the Wnt/β-catenin pathway, indicating that HNF1A-AS1 might be a potential target for the treatment of OS.