Gong Zhe, Zhang Yanqiu, Yang Yue, Yang Yanan, Zhang Jieyun, Wang Yixuan, Zhao Liqin, Yu Nuoya, Wu Zhenhua, Guo Weijian
Department of Gastrointestinal Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Cancers (Basel). 2023 Feb 16;15(4):1261. doi: 10.3390/cancers15041261.
Long noncoding RNAs (lncRNAs) were recently reported to play an essential role in multiple cancer types. Herein, through next-generation sequencing, we screened metastasis-driving molecules by using tissues from early-stage gastric cancer (GC) patients with lymph node metastasis, and we identified a lncRNA LINC01094, which was associated with the metastasis of GC. According to the clinical data from the TCGA, GSE15459, and GSE62254 cohorts, the high expression of LINC01094 was associated with an unfavorable prognosis. Moreover, 106 clinical GC and paired normal samples were collected, and the qRT-PCR results showed that the high expression of LINC01094 was associated with high T and N stages and a poor prognosis. We found that LINC01094 promotes the proliferation and metastasis of GC in vitro and in vivo. AZGP1 was found as the protein-binding partner of LINC01094 by using RNA pulldown and RNA-binding protein immunoprecipitation (RIP) assays. LINC01094 antagonizes the function of AZGP1, downregulates the expression of PTEN, and further upregulates the AKT pathway. Collectively, our results suggested that LINC01094 might predict the prognosis of GC patients and become the therapy target for GC.
最近有报道称长链非编码RNA（lncRNAs）在多种癌症类型中发挥着重要作用。在此，我们通过下一代测序，利用早期胃癌（GC）伴淋巴结转移患者的组织筛选转移驱动分子，鉴定出一种lncRNA LINC01094，它与GC的转移相关。根据来自TCGA、GSE15459和GSE62254队列的临床数据，LINC01094的高表达与不良预后相关。此外，收集了106例临床GC及配对的正常样本，qRT-PCR结果显示LINC01094的高表达与高T和N分期及不良预后相关。我们发现LINC01094在体外和体内均促进GC的增殖和转移。通过RNA下拉和RNA结合蛋白免疫沉淀（RIP）实验，发现AZGP1是LINC01094的蛋白结合伙伴。LINC01094拮抗AZGP1的功能，下调PTEN的表达，并进一步上调AKT通路。总体而言，我们的结果表明LINC01094可能预测GC患者的预后，并成为GC的治疗靶点。
