Department of Gastroenterology, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang 050000, Hebei, China.
Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
Int J Biol Sci. 2022 May 1;18(8):3156-3166. doi: 10.7150/ijbs.68776. eCollection 2022.
LncRNA is closely associated with the progression of human tumors. The role of lncRNA TNFRSF10A-AS1 (T-AS1) in gastric cancer (GC) is still unclear. We aim to investigate the functional significance and the underlying mechanisms of T-AS1 in the pathogenesis and progression of GC. The clinical impact of T-AS1 was assessed in 103 patients with GC. The biological function of T-AS1 was studied and . T-AS1 downstream effector were identified by RNA sequencing and RNA pulldown assay. T-AS1 was upregulated in GC cell lines and GC tissues as compared to adjacent non-cancer tissues (n = 47, < 0.001). Multivariate analysis showed that GC patients with T-AS1 high expression had a significantly shortened survival (n=103, < 0.05). T-AS1 significantly promoted GC cell proliferation, cell-cycle progression, and cell migration/invasion abilities, but suppressed cell apoptosis. Silencing of T-AS1 in GC cells exerted opposite effects . Knockout of T-AS1 significantly inhibited xenograft tumor growth in nude mice. Mechanistically, T-AS1 directly bound to Myelin Protein Zero Like 1 (MPZL1). MPZL1 showed an oncogenic function in GC by promoting cell proliferation, migration and invasion but inhibiting cell apoptosis. High expression of MPZL1 was associated with poor survivor of GC patients. Knockdown of MPZL1 could abrogate the effect of T-AS1 in the tumor-promoting function. T-AS1 plays a pivotal oncogenic role in GC and is an independent prognostic factor for GC patients. The oncogenic function of T-AS1 is dependent on its direct downstream effector MPZL1.
长链非编码 RNA 与人类肿瘤的进展密切相关。长链非编码 RNA TNFRSF10A-AS1（T-AS1）在胃癌（GC）中的作用尚不清楚。我们旨在研究 T-AS1 在 GC 发病机制和进展中的功能意义和潜在机制。在 103 例 GC 患者中评估了 T-AS1 的临床影响。通过 RNA 测序和 RNA 下拉测定研究了 T-AS1 的生物学功能。通过 RNA 测序和 RNA 下拉测定鉴定了 T-AS1 的下游效应子。与相邻非癌组织（n=47，<0.001）相比，GC 细胞系和 GC 组织中 T-AS1 上调。多变量分析显示，T-AS1 高表达的 GC 患者生存时间明显缩短（n=103，<0.05）。T-AS1 显著促进 GC 细胞增殖、细胞周期进程和细胞迁移/侵袭能力，但抑制细胞凋亡。GC 细胞中 T-AS1 的沉默产生了相反的效果。在裸鼠中敲除 T-AS1 显著抑制异种移植肿瘤的生长。机制上，T-AS1 直接与髓鞘蛋白零样 1（MPZL1）结合。MPZL1 通过促进细胞增殖、迁移和侵袭，同时抑制细胞凋亡，在 GC 中发挥致癌作用。MPZL1 的高表达与 GC 患者的生存不良相关。敲低 MPZL1 可消除 T-AS1 在肿瘤促进功能中的作用。T-AS1 在 GC 中发挥关键致癌作用，是 GC 患者的独立预后因素。T-AS1 的致癌功能依赖于其直接下游效应子 MPZL1。
