Department of General Surgery, The No.967 Hospital of PLA Joint Logistics Support Force, Postgraduate Culture Base of Jinzhou Medical University, Dalian, China.
Laboratory of Membrane Ion Channels and Medicine, Key Laboratory of Cognitive Science of State Ethnic Affairs Commission, College of Biomedical Engineering, South- Central University for Nationalities, Wuhan, China.
Arch Med Res. 2021 Oct;52(7):683-691. doi: 10.1016/j.arcmed.2021.04.004. Epub 2021 May 4.
Long noncoding RNAs (lncRNAs) are essential modulators of cancers initiation and progression via regulating gene expression and biological behaviors. LncRNA SAMD12-AS1 has been validated to promote the progression of several cancers, while its role in gastric cancer (GC) remains unclear. This study aims to explore the role of LncRNA SAMD12-AS1 in GC.
qRT-PCR was performed to analyze the expression of lncRNA SAMD12-AS1 in GC tissues and cell lines, with Kaplan-Meier curve analyzing the correlation between LncRNA SAMD12-AS1 and prognosis. CCK-8 assay, and flow cytometry were applied to detect GC cells proliferation, cell cycle. Binding of RNA and proteins were detected via RNA binding protein immunoprecipitation (RIP) assay. Protein levels of oncogenesis-related genes were determined via western blotting.
SAMD12-AS1 was highly up-regulated in human gastric cancer tissues and cell lines compared to their normal counterparts. High SAMD12-AS1 expression was closely related to TNM stage, and shorter survival span of patients with GC. Moreover, SAMD12-AS1 was also found to promote the oncogenic role of GC cells via inhibiting the P53 signaling pathway. Mechanistically, SAMD12-AS1 might performed its biological roles in GC via directly interacting with DNMT1 and facilitating DNMT1 repress the P53 signaling pathway.
Our study demonstrated that SAMD12-AS1 promoted GC progression via DNMT1/P53 axis, indicating SAMD12-AS1 may be envisioned as a novel biomarker of, and therapeutic target for GC.
长链非编码 RNA（lncRNAs）通过调节基因表达和生物行为，是癌症发生和发展的重要调节剂。LncRNA SAMD12-AS1 已被验证可促进几种癌症的进展，但其在胃癌（GC）中的作用尚不清楚。本研究旨在探讨 LncRNA SAMD12-AS1 在 GC 中的作用。
采用 qRT-PCR 分析 GC 组织和细胞系中 lncRNA SAMD12-AS1 的表达，Kaplan-Meier 曲线分析 LncRNA SAMD12-AS1 与预后的相关性。CCK-8 法和流式细胞术检测 GC 细胞增殖、细胞周期。采用 RNA 结合蛋白免疫沉淀（RIP）检测 RNA 与蛋白质的结合。采用 Western blot 检测致癌相关基因的蛋白水平。
SAMD12-AS1 在人胃癌组织和细胞系中的表达明显高于正常对照。高 SAMD12-AS1 表达与 TNM 分期和 GC 患者的生存时间密切相关。此外，SAMD12-AS1 还通过抑制 P53 信号通路促进 GC 细胞的致癌作用。机制上，SAMD12-AS1 可能通过与 DNMT1 直接相互作用并促进 DNMT1 抑制 P53 信号通路来发挥其在 GC 中的生物学作用。
本研究表明，SAMD12-AS1 通过 DNMT1/P53 轴促进 GC 进展，表明 SAMD12-AS1 可作为 GC 的新型标志物和治疗靶点。
