State Key Laboratory of Biotherapy and Cancer Center, West China Hospital and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, 1218 S. Fifth Avenue, Suite 2226, Biomedical Research Center, Monrovia, CA 91016, USA.
Biochim Biophys Acta Rev Cancer. 2021 Apr;1875(2):188519. doi: 10.1016/j.bbcan.2021.188519. Epub 2021 Feb 4.
Cancer metastasis, defined by the epithelial to mesenchymal transition (EMT) of tumor cells, disseminates from the primary site to progressively colonize in distant tissues, and accounts for most cancer-associated deaths. However, studies on the molecular basis of cancer metastasis are still in their infancy. Besides genetic mutations, accumulating evidence indicates that epigenetic alterations also contribute in a major way to the refractory nature of cancer metastasis. Considered as one of the essential epigenetic regulators, long non-coding RNAs (lncRNAs) can act as signaling regulators, decoys, guides and scaffolds, modulating key molecules in every step of cancer metastasis including dissemination of carcinoma cells, intravascular transit, and metastatic colonization. Although still having limited clinical application, it is encouraging to witness that several lncRNAs, including CCAT1 and HOTAIR, are under clinical evaluation as potential biomarkers for cancer staging and assessment of metastatic potential. In this review, we focus on the molecular mechanisms underlying lncRNAs in the regulation of cancer metastasis and discuss their clinical potential as novel therapeutic targets as well as their diagnostic and prognostic significance for cancer treatment. Gaining clear insights into the detailed molecular basis underlying lncRNA-modulated cancer metastasis may provide previously unrecognized diagnostic and therapeutic strategies for metastatic patients.
癌症转移，定义为肿瘤细胞的上皮间质转化（EMT），从原发部位扩散并逐渐在远处组织中定植，是大多数癌症相关死亡的原因。然而，癌症转移的分子基础研究仍处于起步阶段。除了遗传突变，越来越多的证据表明，表观遗传改变也在很大程度上导致了癌症转移的难治性。长链非编码 RNA（lncRNA）被认为是重要的表观遗传调控因子之一，可作为信号调节剂、诱饵、向导和支架，调节癌症转移的每一个步骤中的关键分子，包括癌细胞的扩散、血管内转移和转移性定植。尽管 lncRNA 的临床应用仍有限，但令人鼓舞的是，包括 CCAT1 和 HOTAIR 在内的几种 lncRNA 正在进行临床评估，作为癌症分期和评估转移潜能的潜在生物标志物。在这篇综述中，我们重点介绍了 lncRNA 在调节癌症转移中的分子机制，并讨论了它们作为新型治疗靶点的临床潜力及其在癌症治疗中的诊断和预后意义。深入了解 lncRNA 调节的癌症转移的详细分子基础，可能为转移性患者提供以前未被认识到的诊断和治疗策略。
