Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China.
Department of General Surgery, PLA Strategic Support Force Characteristic Medical Center, Beijing, China.
Curr Cancer Drug Targets. 2024;24(12):1222-1234. doi: 10.2174/0115680096277956240119065938.
Long non-coding RNAs (lncRNAs) are of great importance in the process of colorectal cancer (CRC) tumorigenesis and progression. However, the functions and underlying molecular mechanisms of the majority of lncRNAs in CRC still lack clarity.
A Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect lncRNA NUTM2A-AS1 expression in CRC cell lines. Cell counting kit 8 (CCK-8) assay and flow cytometry were used to examine the biological functions of lncRNA NUTM2A-AS1 in the proliferation and apoptosis of CRC cells. RT-qPCR and western blot were implemented for the detection of cell proliferation-, apoptosis-related proteins, and FAM3C. Bioinformatics analysis and dual- luciferase reporter assays were utilized to identify the mutual regulatory mechanism of ceRNAs.
lncRNA NUTM2A-AS1 notably elevated in CRC cell lines and the silenced of NUTM2A- AS1 declined proliferation and facilitated apoptosis. Mechanistically, NUTM2A-AS1 was transcriptionally activated by histone H3 on lysine 27 acetylation (H3K27ac) enriched at its promoter region, and NUTM2A-AS1 acted as a sponge for miR-126-5p, leading to the upregulation of FAM3C expression in CRC cell lines.
Our research proposed NUTM2A-AS1 as an oncogenic lncRNA that facilitates CRC malignancy by upregulating FAM3C expression, which might provide new insight and a promising therapeutic target for the diagnosis and treatment of CRC.
长链非编码 RNA（lncRNA）在结直肠癌（CRC）肿瘤发生和发展过程中具有重要意义。然而，大多数 lncRNA 在 CRC 中的功能和潜在分子机制仍不清楚。
采用实时定量聚合酶链反应（qRT-PCR）检测 CRC 细胞系中 lncRNA NUTM2A-AS1 的表达。细胞计数试剂盒 8（CCK-8）检测和流式细胞术用于检测 lncRNA NUTM2A-AS1 对 CRC 细胞增殖和凋亡的生物学功能。RT-qPCR 和 Western blot 用于检测细胞增殖、凋亡相关蛋白和 FAM3C。利用生物信息学分析和双荧光素酶报告基因实验鉴定 ceRNA 的相互调节机制。
lncRNA NUTM2A-AS1 在 CRC 细胞系中显著上调，沉默 NUTM2A-AS1 可降低增殖并促进凋亡。机制上，NUTM2A-AS1 由组蛋白 H3 赖氨酸 27 乙酰化（H3K27ac）在其启动子区域上的转录激活，NUTM2A-AS1 作为 miR-126-5p 的海绵，导致 CRC 细胞系中 FAM3C 表达上调。
我们的研究提出 NUTM2A-AS1 作为一种致癌 lncRNA，通过上调 FAM3C 表达促进 CRC 恶性转化，这可能为 CRC 的诊断和治疗提供新的见解和有前途的治疗靶点。
