Lu Chunwei, Ma Jun, Cai Dingfang
Department of Integrated Traditional Chinese and Western Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Tumour Biol. 2017 Apr;39(4):1010428317697574. doi: 10.1177/1010428317697574.
Lung cancers are broadly classified into small cell lung cancer and non-small cell lung cancer, with non-small cell lung cancer one of the leading causes of cancer-associated deaths worldwide. Presently, the mechanisms underlying lung tumorigenesis remain incompletely understood. Accumulating evidence indicates that abnormal expression of long non-coding RNAs is associated with tumorigenesis in multiple cancers, including lung cancer. HAGLR messenger RNA of non-small cell lung cancer tissues was significantly higher. Moreover, high levels of HAGLR expression were associated with non-small cell lung cancer tumor lymph node metastasis status, stage, and poor overall survival. Inhibition of HAGLR in non-small cell lung cancer cells suppressed cell proliferation and invasion. RNA interference-mediated downregulation of HAGLR also decreased levels of fatty acid synthase, with fatty acid synthase levels positively correlated with HAGLR expression in non-small cell lung cancer specimens. In addition, the cellular free fatty acid content of cancer cells was decreased following HAGLR knockdown. HAGLR depletion significantly inhibited the growth of non-small cell lung cancer cells in vivo. Furthermore, the expression levels of p21 and matrix metallopeptidase-9 (MMP-9) were dysregulated when HAGLR expression was suppressed. Our results suggest that HAGLR is an important regulator of non-small cell lung cancer cell proliferation and invasion, perhaps by regulating fatty acid synthase. Therefore, targeting HAGLR may be a possible therapeutic strategy for non-small cell lung cancer.
肺癌大致分为小细胞肺癌和非小细胞肺癌，其中非小细胞肺癌是全球癌症相关死亡的主要原因之一。目前，肺癌发生的潜在机制仍未完全了解。越来越多的证据表明，长链非编码RNA的异常表达与包括肺癌在内的多种癌症的发生有关。非小细胞肺癌组织中的HAGLR信使核糖核酸显著更高。此外，高水平的HAGLR表达与非小细胞肺癌肿瘤淋巴结转移状态、分期及总体生存率差相关。抑制非小细胞肺癌细胞中的HAGLR可抑制细胞增殖和侵袭。RNA干扰介导的HAGLR下调也降低了脂肪酸合酶的水平，在非小细胞肺癌标本中脂肪酸合酶水平与HAGLR表达呈正相关。此外，HAGLR敲低后癌细胞的细胞游离脂肪酸含量降低。HAGLR缺失显著抑制了非小细胞肺癌细胞在体内的生长。此外，当HAGLR表达受到抑制时，p21和基质金属肽酶9（MMP-9）的表达水平失调。我们的结果表明，HAGLR可能通过调节脂肪酸合酶，是非小细胞肺癌细胞增殖和侵袭的重要调节因子。因此，靶向HAGLR可能是非小细胞肺癌的一种潜在治疗策略。
