Li Peng, Xue Wan-Jiang, Feng Ying, Mao Qin-Sheng
Department of Surgery, Affiliated Hospital of Nantong University Nantong, 226001, China.
Am J Transl Res. 2016 Aug 15;8(8):3522-9. eCollection 2016.
Long non-coding RNAs (lncRNAs) have been shown to play important roles in tumorigenesis. However, the biological functions and molecular mechanisms underlying aberrantly expressed lncRNAs in gastric cancer (GC) is still unclear. In this study, a novel lncRNA CASC2 was chosen to evaluate the effect on GC cell growth and the possible mechanism. Our results showed that CASC2 was significantly downregulated in human GC tissues and cell lines by quantitative RT-PCR. Overexpression of CASC2 in GC cells significantly inhibited the cell growth in vitro and in vivo. We further found that MAPK pathway especially the ERK1/2 and JNK component were involved in the CASC2 mediated GC cell proliferation. Moreover, combination treatment of CASC2 overexpression and suppression ERK1/2 or JNK produced synergistic inhibitory effects in vitro. Thus, these results indicated that CASC2 might serve as a tumor suppressor lncRNA that suppressed cell proliferation by inactivation of MAPK pathway. These findings suggested that CASC2 could be a potential therapeutic target for the treatment of GC patients.
长链非编码RNA（lncRNAs）已被证明在肿瘤发生中发挥重要作用。然而，胃癌（GC）中异常表达的lncRNAs的生物学功能和分子机制仍不清楚。在本研究中，选择了一种新型lncRNA CASC2来评估其对GC细胞生长的影响及可能的机制。我们的结果表明，通过定量RT-PCR检测，CASC2在人GC组织和细胞系中显著下调。在GC细胞中过表达CASC2可显著抑制其体外和体内生长。我们进一步发现，MAPK通路尤其是ERK1/2和JNK组分参与了CASC2介导的GC细胞增殖。此外，CASC2过表达与抑制ERK1/2或JNK的联合处理在体外产生了协同抑制作用。因此，这些结果表明，CASC2可能作为一种肿瘤抑制性lncRNA，通过使MAPK通路失活来抑制细胞增殖。这些发现提示，CASC2可能是治疗GC患者的一个潜在治疗靶点。
