长链非编码RNA WT1-AS对胃癌肿瘤干细胞生物学特性的调控作用及其机制研究

Gastric cancer (GC) remains one of the leading causes of global cancer mortality. Gastric cancer stem cells (GCSC) played an essential role in the initiation and development of GC. More and more evidences suggested that Long noncoding RNAs (lncRNAs) are the key regulator of GCSC. There is little research on regulation of GCSC by lncRNAs. Our previous work revealed that lncRNA-WT1-AS expression was significantly down-regulated in GC tissues compared to matched adjacent non-tumor tissues. The WT1-AS expression was associated with tumor size and the clinicopathological stage. Cell proliferation, migration, and invasion were inhibited when WT1-AS was ectopically-expressed both in vitro and in vivo, but the detailed mechanism by which WT1-AS regulated GC remains unclear, and GCSC is the essential element in GC invasion and metastasis, so we presume that WT1-AS could regulate GCSC biological characteristics (like metastasis) by targeting some key signal pathway (like EMT). The knowledge gained by studying relationship of lncRNA-WT1-AS and GCSC will support the development of novel therapeutic strategies for GC.

胃癌仍是世界上肿瘤相关死亡的主要原因。胃癌肿瘤干细胞（gastric cancer stem cells ,GCSC）在胃癌的发生发展中起着关键作用。诸多研究表明长链非编码RNA（long noncoding RNAs, lncRNAs）是肿瘤干细胞的关键调控因子，但lncRNAs对胃癌干细胞的调控机制鲜有报道。我们前期研究发现，lncRNA-WT1-AS在胃癌组织中低表达，其表达水平与肿瘤的大小及临床分期显著相关。体内外实验证实过表达WT1-AS可明显抑制胃癌细胞的增殖、侵袭、迁移等生物学特性，但具体机制仍不清楚，而研究表明胃癌干细胞才是胃癌侵袭转移的“罪魁祸首”，所以，我们推测WT1-AS可通过靶向特定信号通路（如EMT）调控胃癌干细胞的生物学特性（转移）参与胃癌的发生发展。LncRNAs-WT1-AS对GCSC表型调控的研究必将有助于胃癌治疗新策略的发展。

胃癌仍是世界上肿瘤相关死亡的主要原因。胃癌肿瘤干细胞（gastric cancer stem cells ,GCSC）在胃癌的发生发展中起着关键作用。诸多研究表明长链非编码RNA（long noncoding RNAs, lncRNAs）是肿瘤干细胞的关键调控因子，但lncRNAs对胃癌干细胞的调控机制鲜有报道。我们前期研究发现，lncRNA-WT1-AS在胃癌组织中低表达，其表达水平与肿瘤的大小及临床分期显著相关。体内外实验证实过表达WT1-AS可明显抑制胃癌细胞的增殖、侵袭、迁移等生物学特性，但具体机制仍不清楚，而研究表明胃癌干细胞才是胃癌侵袭转移的“罪魁祸首”，我们推测WT1-AS可通过靶向特定信号通路（如EMT）调控胃癌干细胞的生物学特性（转移）参与胃癌的发生发展。本课题研究发现，过表达WT1-AS可抑制胃癌干细胞增殖、侵袭、迁移、EMT通路活性，促进胃癌干细胞凋亡，抑制其细胞周期进展，并且能够降低胃癌干细胞对化疗药物的耐药性等。LncRNAs-WT1-AS对GCSC表型调控的研究必将有助于胃癌治疗新策略的发展。