Fang Changyi, Qiu Shenglong, Sun Feng, Li Wei, Wang Ziqi, Yue Ben, Wu Xuesong, Yan Dongwang
Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, China.
Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, China.
Cancer Lett. 2017 Dec 1;410:50-62. doi: 10.1016/j.canlet.2017.09.012. Epub 2017 Sep 21.
In recent years, accumulating evidence indicates that long noncoding RNAs (lncRNAs) have emerged as powerful influence factors in the progression of multiple malignancies. Dysregulation of lncRNA HNF1A-antisense 1 (HNF1A-AS1) has been reported in many types of human cancers, and studies on HNF1A-AS1 function in cancers revealed that HNF1A-AS1could act as either oncogene or tumor suppressor. Nevertheless, the functional involvement of HNF1A-AS1 in colon cancer remains unknown. In this study, we reported that HNF1A-AS1 was frequently upregulated in colon cancer tissues and associated with poor prognosis. Upregulated HNF1A-AS1 promoted colon cancer cell viability, migration and invasion both in vitro and in vivo. HNF1A-AS1 silencing impaired tumor growth and metastasis in xenograft model assay. Moreover, HNF1A-AS1 functioned as an oncogene in metastasis of colon cancer in part through serving as a competing endogenous RNA to modulate miRNA-34a expression, subsequently with repression of miR-34a/SIRT1/p53 feedback loop and activation of canonical Wnt signaling pathway. Our results demonstrated that HNF1A-AS1 mediated the metastatic progression of colon cancer in part through miR-34a/p53 signaling axis, and established its candidacy as a new prognostic biomarker and a potential novel therapeutic target.
近年来,越来越多的证据表明,长链非编码RNA(lncRNA)已成为多种恶性肿瘤进展中的强大影响因素。在许多类型的人类癌症中都报道了lncRNA HNF1A反义1(HNF1A-AS1)的失调,对HNF1A-AS1在癌症中的功能研究表明,HNF1A-AS1既可以作为癌基因,也可以作为肿瘤抑制因子。然而,HNF1A-AS1在结肠癌中的功能作用仍不清楚。在本研究中,我们报道HNF1A-AS1在结肠癌组织中经常上调,并与不良预后相关。上调的HNF1A-AS1在体外和体内均促进结肠癌细胞的活力、迁移和侵袭。在异种移植模型试验中,HNF1A-AS1沉默会损害肿瘤生长和转移。此外,HNF1A-AS1在结肠癌转移中作为癌基因发挥作用,部分原因是作为竞争性内源性RNA调节miRNA-34a的表达,随后抑制miR-34a/SIRT1/p53反馈环并激活经典Wnt信号通路。我们的结果表明,HNF1A-AS1部分通过miR-34a/p53信号轴介导结肠癌的转移进展,并确立了其作为新的预后生物标志物和潜在新治疗靶点的候选地位。
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