Department of Geriatrics, The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University, Wuhan, Hubei, China.
Department of Cardiovascular Medicine, Wuhan Asia Heart Hospital, Wuhan, Hubei, China.
Cancer Biomark. 2023;38(3):333-342. doi: 10.3233/CBM-230103.
Numerous evidence have suggested the vital role of lncRNAs in human tumorigenesis. And lncRNA APAP1-AS1 has been proved to act as an oncogene.
Nevertheless, the molecular process underlying ARAP1-AS1 for the lymphoma progression has not been well studied.
RT-qPCR was used to ascertain the miR-6867-5p and ARAP1-AS1 in lymphoma cells and tissues. The localization of ARAP1-AS1 was determined via subcellular fractionation analysis. A xenograft model was used to investigate the influence of ARAP1-AS1 in formation of tumor in vivo. In addition, interactions between ARAP-AS1 and miR-6867-5p were tested by bioinformatics analysis, RIP assay, luciferase reporter and Pearson's correlation analysis. Combined with loss-of-function experiments, MTT assays and flow cytometry were performed to evaluate the function of miR-6867-5p and also ARAP-AS1 in proliferation and apoptosis of lymphoma cells, respectively.
ARAP1-AS1 was remarkably upregulated in lymphoma cells and tissues, while miR-6867-5p expression was downregulated. Furthermore, high ARAP1-AS1 expression suppressed miR-6867-5p expression in lymphoma cell lines (Raji and CA46), and Pearson's analysis showed negative correlation between ARAP1-AS1 expression and also miR-6867-5p expression. In addition, knockdown of ARAP1-AS1 resulted in weakened cell viability and uplifted apoptosis rate of lymphoma cells (Raji and CA46) as well as a delay in the tumor growth in vivo. Further investigations illustrated that miR-6867-5p inhibitor reversed all above biological activities.
LncRNA ARAP1-AS1 served as a tumor-promoter in lymphoma cells by sponging with miR-6867-5p, which may help to provide potential therapeutic target gene for lymphoma patients.
大量证据表明 lncRNA 在人类肿瘤发生中起着至关重要的作用。并且已经证明 lncRNA APAP1-AS1 是一种癌基因。
然而，ARAP1-AS1 促进淋巴瘤进展的分子机制尚未得到很好的研究。
采用 RT-qPCR 检测淋巴瘤细胞和组织中的 miR-6867-5p 和 ARAP1-AS1。通过亚细胞分离分析确定 ARAP1-AS1 的定位。使用异种移植模型研究 ARAP1-AS1 在体内肿瘤形成中的影响。此外，通过生物信息学分析、RIP 测定、荧光素酶报告和 Pearson 相关性分析测试 ARAP-AS1 与 miR-6867-5p 之间的相互作用。结合功能丧失实验，分别进行 MTT 测定和流式细胞术，以评估 miR-6867-5p 和 ARAP1-AS1 对淋巴瘤细胞增殖和凋亡的功能。
ARAP1-AS1 在淋巴瘤细胞和组织中显著上调，而 miR-6867-5p 的表达下调。此外，高表达 ARAP1-AS1 抑制淋巴瘤细胞系（Raji 和 CA46）中的 miR-6867-5p 表达，Pearson 分析显示 ARAP1-AS1 表达与 miR-6867-5p 表达呈负相关。此外，敲低 ARAP1-AS1 导致淋巴瘤细胞（Raji 和 CA46）的细胞活力减弱和凋亡率升高，以及体内肿瘤生长延迟。进一步的研究表明，miR-6867-5p 抑制剂逆转了所有上述生物学活性。
lncRNA ARAP1-AS1 通过与 miR-6867-5p 结合在淋巴瘤细胞中起肿瘤促进作用，这可能有助于为淋巴瘤患者提供潜在的治疗靶基因。
