Liu Bin, Lu Tingting, Zhang Guangming, Dong Xiaohua, Yu Miao, Cai Hui
The First School of Clinical Medicine, Lanzhou University, Lanzhou, China.
NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou, China.
J Cell Mol Med. 2025 Jun;29(11):e70652. doi: 10.1111/jcmm.70652.
The current study investigated the functional role of long non-coding RNA SNHG14 (lncRNA SNHG14) in gastric cancer (GC) progression and its underlying mechanisms. Compared with para-carcinoma tissues, SNHG14 was upregulated in GC tissues, correlating with a poor prognosis in GC patients. SNHG14 knockdown significantly weakened the proliferation, migration and invasion capabilities of GC cell lines while enhancing the apoptosis ability of GC cells. Simultaneously, SNHG14 overexpression reversed these effects. RNA fluorescence in situ hybridization (FISH) and nucleocytoplasmic separation assays revealed that SNHG14 was primarily located in the cytoplasm of GC cells. Combined sequencing of the miRNAome and transcriptome depicted that miR-206 could be a potential target for SNHG14. Mechanistically, assays such as luciferase reporter, RNA immunoprecipitation (RIP) and RNA pulldown established that lncRNA SNHG14 acted as a sponge for miR-206. This prevented the degradation of its target gene, FNDC3A, playing a tumour-suppressive role in GC. In addition, FNDC3A directly interacted with the SNHG14 promoter and induced transcription, thus facilitating GC progression. Therefore, our research findings suggested a novel pathway to promote GC progression through the FNDC3A/lncRNA SNHG14/miR-206/FNDC3A axis. Moreover, the findings indicated that SNHG14 could become a potential biomarker and therapeutic target for GC.
本研究探讨了长链非编码RNA SNHG14(lncRNA SNHG14)在胃癌(GC)进展中的功能作用及其潜在机制。与癌旁组织相比,SNHG14在GC组织中上调,这与GC患者的不良预后相关。SNHG14敲低显著削弱了GC细胞系的增殖、迁移和侵袭能力,同时增强了GC细胞的凋亡能力。同时,SNHG14过表达逆转了这些作用。RNA荧光原位杂交(FISH)和核质分离试验表明,SNHG14主要位于GC细胞的细胞质中。miRNAome和转录组的联合测序表明,miR-206可能是SNHG14的潜在靶点。机制上,荧光素酶报告基因、RNA免疫沉淀(RIP)和RNA下拉等试验证实lncRNA SNHG14作为miR-206的海绵。这阻止了其靶基因FNDC3A的降解,在GC中发挥肿瘤抑制作用。此外,FNDC3A直接与SNHG14启动子相互作用并诱导转录,从而促进GC进展。因此,我们的研究结果提示了一条通过FNDC3A/lncRNA SNHG14/miR-206/FNDC3A轴促进GC进展的新途径。此外,研究结果表明SNHG14可能成为GC的潜在生物标志物和治疗靶点。