Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
Stem Cell and Regenerative Medicine Research Group, Academic Center for Education, Culture, and Research (ACECR), Khorasan Razavi, Mashhad, Iran.
Life Sci. 2022 Sep 15;305:120759. doi: 10.1016/j.lfs.2022.120759. Epub 2022 Jul 2.
Gastric cancer (GC) is one of the most common lethal malignancies worldwide. The molecular mechanisms underlying GC early detection are poorly understood. Identifying potential coding and non-coding markers and related pathways in the GC progression is essential. Some Long non-coding RNAs (lncRNAs) reportedly play vital roles during gastric GC development. However, the clinical significance and biological function of LINC00332 in GC remain largely unclear.
The gene expression patterns of GC from an RNAseq dataset (GSE122401) were retrieved from the Gene Expression Omnibus (GEO) database to recognize differentially expressed genes (DEGs) and lncRNAs (DELs) between normal and GC samples through several bioinformatic analysis. The expression of LINC00332 and MMP-13 as a target gene was quantified in fresh frozen tissues obtained from GC patients. In addition, we investigated the potential function of LINC00332 in silico and in vitro.
The expressions of LINC00332 and MMP-13 were significantly downregulated and upregulated in GC tissues, respectively. A significant inverse correlation between LINC00332 and MMP-13 mRNA expression was observed in tumor samples. The mRNA expression level of mesenchymal markers, stem cell factors, and MMP genes were significantly decreased after the LINC00332 ectopic expression, while epithelial markers expression was significantly increased. The LINC00332 overexpression markedly repressed proliferation, migration, and invasion and did not induce apoptosis in AGS cells. In addition, LINC00332 overexpression notably promoted the E-cadherin protein expression. Moreover, LINC00332 significantly decreased the cisplatin resistance.
Our findings indicated that LINC00332 may be a critical anti-EMT factor and provided a new efficient therapeutic strategy for GC treatment.
胃癌（GC）是全球最常见的致命恶性肿瘤之一。GC 早期检测的分子机制尚不清楚。确定 GC 进展过程中的潜在编码和非编码标志物及相关途径至关重要。一些长链非编码 RNA（lncRNA）据报道在胃 GC 发展中发挥重要作用。然而，LINC00332 在 GC 中的临床意义和生物学功能仍很大程度上不清楚。
从基因表达综合数据库（GEO）中检索了一个 RNAseq 数据集（GSE122401）中的 GC 基因表达图谱，通过几种生物信息学分析，识别正常和 GC 样本之间差异表达的基因（DEGs）和 lncRNA（DELs）。在 GC 患者的新鲜冷冻组织中定量检测 LINC00332 和 MMP-13 作为靶基因的表达。此外，我们还进行了 LINC00332 的计算机模拟和体外研究。
LINC00332 和 MMP-13 的表达在 GC 组织中分别显著下调和上调。在肿瘤样本中观察到 LINC00332 和 MMP-13 mRNA 表达之间存在显著的负相关。外源性表达 LINC00332 后，间充质标志物、干细胞因子和 MMP 基因的 mRNA 表达水平显著降低，而上皮标志物的表达水平显著增加。LINC00332 的过表达显著抑制 AGS 细胞的增殖、迁移和侵袭，而不会诱导细胞凋亡。此外，LINC00332 过表达显著促进 E-钙粘蛋白蛋白的表达。此外，LINC00332 显著降低了顺铂耐药性。
我们的研究结果表明，LINC00332 可能是一种关键的抗 EMT 因子，为 GC 的治疗提供了一种新的有效治疗策略。
