Department of Clinical and Military Laboratory Medicine, College of Medical Laboratory Science, Army Medical University, Chongqing, China.
College of Pharmacy, Chongqing Medical University, Chongqing, China.
J Cell Physiol. 2021 Jan;236(1):536-548. doi: 10.1002/jcp.29881. Epub 2020 Jun 18.
Although the incidence and mortality of gastric cancer (GC) are slowly decreasing, the overall prognosis of GC patients with distal metastasis remains dismal. Long non-coding RNA PVT1 has been verified to function as a tumor promoter in several types of cancer. However, the role of PVT1 in GC metastasis remains obscure. Herein, we found that PVT1 was highly expressed in GC tissues and high PVT1 level was associated with tumor stage, lymph node metastasis, and poor prognosis. Overexpression of PVT1 significantly elevated epithelial-to-mesenchymal transition (EMT) marker (N-cadherin, ZEB1, and ZEB2) levels and promoted GC cell EMT process and tumor metastasis in vitro and in vivo. Mechanistically, Snail was identified as a direct target of miR-30a. PVT1 could bind with miR-30a and increase the expression of Snail by acting as a competing endogenous RNA, whereas re-expression of miR-30a in GC cells rescued the EMT markers, decreased Snail level, and inhibited GC cell migration. Taken together, these findings provide a new light on PVT1 in the pathogenesis and development of GC and an important implication for future therapy of the GC.
尽管胃癌(GC)的发病率和死亡率正在缓慢下降,但远端转移的 GC 患者的总体预后仍然不佳。长链非编码 RNA PVT1 已被证实在几种类型的癌症中发挥肿瘤促进作用。然而,PVT1 在 GC 转移中的作用仍不清楚。本研究发现,PVT1 在 GC 组织中高表达,高 PVT1 水平与肿瘤分期、淋巴结转移和预后不良有关。过表达 PVT1 可显著提高上皮间质转化(EMT)标志物(N-钙黏蛋白、ZEB1 和 ZEB2)水平,并促进 GC 细胞 EMT 过程和体内外肿瘤转移。机制上,Snail 被鉴定为 miR-30a 的直接靶标。PVT1 可以通过作为竞争性内源性 RNA 与 miR-30a 结合,增加 Snail 的表达,而在 GC 细胞中重新表达 miR-30a 可挽救 EMT 标志物,降低 Snail 水平,并抑制 GC 细胞迁移。总之,这些发现为 PVT1 在 GC 的发病机制和发展中的作用提供了新的认识,并为 GC 的未来治疗提供了重要意义。