Department of Endoscopy Center, First People's Hospital of Wenling, Wenling, Zhejiang, China.
Bioengineered. 2021 Dec;12(2):9678-9691. doi: 10.1080/21655979.2021.1983276.
Gastric cancer (GC) is a common cancer with high incidence. Understanding the epidemiology and physiopathology of GC is crucial for formulating novel therapeutic strategies. Recent studies have implicated long non-coding RNA LINC00240, miR-338-5p and methyltransferase-like 3 (METTL3) in the progression of GC. In this study, we investigated the functional role of LINC00240/miR-338-5p/METTL3 axis in regulating the aggressiveness of GC cells. We first demonstrated that LINC00240 was upregulated in GC tissues and GC cell lines. High expression of LINC00240 was associated with advanced TNM stage, a higher extent of distant metastasis and lymph nodes metastasis, and the poor overall and disease-free survival of the patients. In GC cell lines, the knockdown of LINC00240 inhibited GC cell proliferation and migration, but induced cell apoptosis. We further identified and validated the functional interaction between LINC00240 and miR-338-5p. miR-338-5p seemed to function as a downstream target negatively regulated by LINC00240, and miR-338-5p could target METTL3 at 3' UTR to downregulate its expression. In GC tissues, the expression of miR-338-5p was negatively correlated with LINC00240, and the expression of miR-338-5p was negatively correlated with METTL3. Importantly, miR-338-5p inhibitor or METTL3 overexpression could rescue the inhibitory effect of LINC00240 knockdown on cell proliferation and migration, and inhibit the apoptosis induction in GC cells. Taken together, our data imply that the upregulation of LINC00240 in GC cells promotes the malignant phenotype by modulating miR-338-5p/METTL3 axis, which could serve as potential therapeutic targets for GC treatment.
胃癌（GC）是一种常见的高发病率癌症。了解 GC 的流行病学和病理生理学对于制定新的治疗策略至关重要。最近的研究表明，长链非编码 RNA LINC00240、miR-338-5p 和甲基转移酶样 3（METTL3）参与了 GC 的进展。在本研究中，我们研究了 LINC00240/miR-338-5p/METTL3 轴在调节 GC 细胞侵袭性中的功能作用。我们首先证明 LINC00240 在 GC 组织和 GC 细胞系中上调。LINC00240 的高表达与晚期 TNM 分期、远处转移和淋巴结转移程度较高以及患者的总体和无病生存率较差相关。在 GC 细胞系中，LINC00240 的敲低抑制了 GC 细胞的增殖和迁移，但诱导了细胞凋亡。我们进一步鉴定和验证了 LINC00240 和 miR-338-5p 之间的功能相互作用。miR-338-5p 似乎作为 LINC00240 的下游靶基因负调控，miR-338-5p 可以靶向 3'UTR 下调 METTL3 的表达。在 GC 组织中，miR-338-5p 的表达与 LINC00240 呈负相关，miR-338-5p 的表达与 METTL3 呈负相关。重要的是，miR-338-5p 抑制剂或 METTL3 过表达可以挽救 LINC00240 敲低对 GC 细胞增殖和迁移的抑制作用，并抑制 GC 细胞的凋亡诱导。总之，我们的数据表明，GC 细胞中 LINC00240 的上调通过调节 miR-338-5p/METTL3 轴促进恶性表型，这可能成为 GC 治疗的潜在治疗靶点。
