Wang Qinghua, Jiang Shujun, Song Anying, Hou Siyuan, Wu Qinfeng, Qi Longju, Gao Xiang
State Key Laboratory of Pharmaceutical Biotechnology.
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing.
Onco Targets Ther. 2017 Sep 28;10:4753-4763. doi: 10.2147/OTT.S143787. eCollection 2017.
Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide, and it occurs at a higher frequency in males. HOXD-AS1, an important cancer-associated long noncoding RNA (lncRNA), contributes to the development and progression of several cancers. However, the exact roles of HOXD-AS1 in NSCLC progression are still unknown. Here, we investigated the underlying mechanisms of HOXD-AS1 in human NSCLC tissues. We found that lncRNA HOXD-AS1 was specifically upregulated (<0.001) in NSCLC tissues and promoted cancer cell growth by targeting miR-147a. Moreover, HOXD-AS1 expression positively correlated with NSCLC clinical pathologic characteristics (tumor size, =0.006; tumor stage, =0.044; recurrence, =0.031) and survival rate (=0.003). HOXD-AS1 knockdown reduced proliferation and promoted apoptosis of NSCLC cells. The dual-luciferase reporter assay showed that HOXD-AS1 could negatively regulate the expression of miR-147a. miR-147a inhibition abrogated the effect of HOXD-AS1 knockdown on the proliferation and apoptosis of NSCLC cells. Furthermore, HOXD-AS1 positively regulated the expression of pRB (a tumor suppressor protein) in NSCLC cells. Taken together, our data indicated that HOXD-AS1 might be an oncogenic lncRNA that promotes proliferation of NSCLC and could be a therapeutic target in NSCLC.
非小细胞肺癌（NSCLC）是全球最常见的恶性肿瘤之一，在男性中发病率更高。HOXD-AS1是一种重要的癌症相关长链非编码RNA（lncRNA），在多种癌症的发生和发展中起作用。然而，HOXD-AS1在NSCLC进展中的确切作用仍不清楚。在此，我们研究了HOXD-AS1在人NSCLC组织中的潜在机制。我们发现lncRNA HOXD-AS1在NSCLC组织中特异性上调（<0.001），并通过靶向miR-147a促进癌细胞生长。此外，HOXD-AS1表达与NSCLC临床病理特征（肿瘤大小，=0.006；肿瘤分期，=0.044；复发，=0.031）和生存率（=0.003）呈正相关。HOXD-AS1敲低可降低NSCLC细胞的增殖并促进其凋亡。双荧光素酶报告基因检测表明HOXD-AS1可负调控miR-147a的表达。抑制miR-147a可消除HOXD-AS1敲低对NSCLC细胞增殖和凋亡的影响。此外，HOXD-AS1在NSCLC细胞中正向调控pRB（一种肿瘤抑制蛋白）的表达。综上所述，我们的数据表明HOXD-AS1可能是一种致癌lncRNA，可促进NSCLC的增殖，可能成为NSCLC的治疗靶点。
