Department of General Surgery; Xinhua Hospital; Shanghai Jiao Tong University School of Medicine; Shanghai, PR China; Laboratory of General Surgery, Xinhua Hospital; Shanghai Jiao Tong University School of Medicine; Shanghai, PR China; Institute of Biliary Tract Disease; Shanghai Jiao Tong University School of Medicine; Shanghai, PR China.
Department of Gastrointestinal Surgery; Shaoxing People's Hospital; Shaoxing, PR China.
Cancer Biol Ther. 2014 Jun 1;15(6):806-14. doi: 10.4161/cbt.28584. Epub 2014 Mar 21.
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long non-coding RNA (lncRNA), is associated with metastasis and is an independent prognostic factor for lung cancer. Recent studies have demonstrated that MALAT1 plays an important role in other malignancies. However, little is known about the role of MALAT1 in gallbladder carcinoma (GBC), which is the most common cancer of the biliary tract and has an extremely poor prognosis. In this study, we focused on the expression, biological functions and mechanism of MALAT1 in GBC and found that MALAT1 was significantly upregulated in GBC tissues compared with corresponding non-cancerous tissues. Knockdown of MALAT1 in GBC cell lines using lentivirus-mediated RNA interference significantly inhibited the proliferation and metastasis of the GBC cells both in vitro and in vivo. Furthermore, ERK/MAPK pathway was found to be inactivated in the GBC cell lines after MALAT1 knockdown. These results indicated that MALAT1 might serve as an oncogenic lncRNA that promotes proliferation and metastasis of GBC and activates the ERK/MAPK pathway.
转移相关肺腺癌转录本 1(MALAT1)是一种长链非编码 RNA(lncRNA),与转移有关,是肺癌的一个独立预后因素。最近的研究表明,MALAT1 在其他恶性肿瘤中发挥着重要作用。然而,关于 MALAT1 在胆囊癌(GBC)中的作用知之甚少,GBC 是胆道最常见的癌症,预后极差。在这项研究中,我们专注于 MALAT1 在 GBC 中的表达、生物学功能和机制,发现与相应的非癌组织相比,MALAT1 在 GBC 组织中明显上调。使用慢病毒介导的 RNA 干扰敲低 GBC 细胞系中的 MALAT1,显著抑制了 GBC 细胞在体外和体内的增殖和转移。此外,在 MALAT1 敲低后,GBC 细胞系中的 ERK/MAPK 通路被发现失活。这些结果表明,MALAT1 可能作为一种致癌 lncRNA,促进 GBC 的增殖和转移,并激活 ERK/MAPK 通路。