Department of General Surgery, Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, Jiangsu, China.
Histol Histopathol. 2019 Jun;34(6):619-630. doi: 10.14670/HH-18-043. Epub 2018 Sep 19.
Recent studies highlight long non-coding RNAs (lncRNAs) as key regulators of cancer biology that contribute to carcinogenesis. The lncRNA HOXA transcript at the distal tip (HOTTIP) is involved in the development of several cancers. Previous studies demonstrated that HOTTIP could promote colorectal cancer (CRC) cell proliferation via silencing of p21 expression. However, the potential role of HOTTIP in CRC metastasis has not yet been discussed. Here, we found that HOTTIP level was significantly higher in CRC than in corresponding adjacent normal tissues, and patients with a larger tumor size, advanced pathological stage, or distant metastasis had higher HOTTIP expression. Moreover, silencing HOTTIP expression by siRNA or shRNA could inhibit CRC cell migration and invasion in vitro and in vivo, whereas HOTTIP overexpression promoted cell metastasis, as documented in the SW480 cell lines. Mechanistic analyses indicated that HOTTIP regulates CRC cell metastasis partly through the downregulation of tumor suppressor DKK1 expression. Collectively, our results suggest that tumor expression of lncRNA HOTTIP plays an important role in CRC metastasis. HOTTIP may serve as a candidate biomarker in this disease.
最近的研究强调了长非编码 RNA（lncRNA）作为癌症生物学的关键调节剂的作用，它们有助于癌症的发生。位于远端尖端的 HOXA 转录本（HOTTIP）参与了多种癌症的发展。先前的研究表明，HOTTIP 可以通过沉默 p21 的表达来促进结直肠癌（CRC）细胞的增殖。然而，HOTTIP 在 CRC 转移中的潜在作用尚未被讨论。在这里，我们发现 HOTTIP 在 CRC 中的水平明显高于相应的相邻正常组织，并且肿瘤较大、病理分期较晚或远处转移的患者 HOTTIP 表达水平更高。此外，通过 siRNA 或 shRNA 沉默 HOTTIP 的表达可以抑制 CRC 细胞在体外和体内的迁移和侵袭，而 HOTTIP 的过表达则促进了细胞转移，这在 SW480 细胞系中得到了证实。机制分析表明，HOTTIP 通过下调肿瘤抑制因子 DKK1 的表达来部分调节 CRC 细胞的转移。总之，我们的结果表明，lncRNA HOTTIP 的肿瘤表达在 CRC 转移中起着重要作用。HOTTIP 可能作为该疾病的候选生物标志物。
