The Long Noncoding RNA DUXAP8 Facilitates the Malignant Progression of Colon Cancer via the microRNA-378a-3p/FOXQ1 Axis.

IF 3.4 3区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY Gut and Liver Pub Date : 2024-11-20 DOI:10.5009/gnl240178

Rui Shang, Jianqin Jin, Yuecheng Wang

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Abstract

Background/aims: The long noncoding RNA DUXAP8 is a pivotal regulator in cancer pathogenesis, but the molecular mechanism underlying the role of DUXAP8 in colon cancer progression is underexplored.

Methods: In addition to bioinformatic analyses, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was performed to assess DUXAP8, microRNA-378a-3p, FOXQ1 expression in colon cancer tissues, and clinical data were analyzed to determine the correlation between DUXAP8 expression and colon cancer patient outcomes. Nuclear/cytoplasmic RNA fractionation was utilized to analyze the subcellular distribution of DUXAP8. Dual-luciferase and RNA immunoprecipitation assays were performed to confirm the binding of DUXAP8/FOXQ1 and microRNA-378a-3p. After cell transfection, qRT-PCR was performed to evaluate the modulatory relationship of DUXAP8/microRNA-378a-3p/FOXQ1. Cell Counting Kit-8, MTT, scratch healing, and Transwell assays were performed to evaluate the impact of DUXAP8/microRNA-378a-3p/FOXQ1 expression on colon cancer cell functions.

Results: The results revealed that the expression of DUXAP8 and FOXQ1 was upregulated in colon cancer tissues, while the expression of microRNA-378a-3p was down-regulated. The increased DUXAP8 expression was positively correlated with lymph node metastasis and TNM stage. Dual-luciferase and RNA immunoprecipitation assays demonstrated that DUXAP8 was a sponge for microRNA-378a-3p and targeted the ability of microRNA-378a-3p to regulate FOXQ1. In addition, functional experiment results revealed that overexpressed DUXAP8 facilitated the growth and migratory ability of colon cancer cells. DUXAP8 also reversed the tumor-suppressive effect of microRNA-378a-3p. However, silencing FOXQ1 could reverse the cancer-promoting effects of high DUXAP8 expression.

Conclusions: DUXAP8 expression was significantly increased in colon cancer, which was associated with lymph node metastasis and unfavorable outcomes in colon cancer patients. DUXAP8 may hasten malignant progression of colon cancer cells through its effects on microRNA-378a-3p/FOXQ1.

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长非编码 RNA DUXAP8 通过 microRNA-378a-3p/FOXQ1 轴促进结肠癌的恶性进展

背景/目的：长非编码 RNA DUXAP8 是癌症发病机制中的关键调控因子，但 DUXAP8 在结肠癌进展中的作用的分子机制尚未得到充分探索：除生物信息学分析外，还进行了定量反转录聚合酶链反应（qRT-PCR）以评估结肠癌组织中 DUXAP8、microRNA-378a-3p 和 FOXQ1 的表达，并分析了临床数据以确定 DUXAP8 表达与结肠癌患者预后之间的相关性。利用核/细胞质 RNA 分馏分析了 DUXAP8 的亚细胞分布。进行了双荧光素酶和 RNA 免疫沉淀试验，以确认 DUXAP8/FOXQ1 与 microRNA-378a-3p 的结合。细胞转染后，进行 qRT-PCR 以评估 DUXAP8/microRNA-378a-3p/FOXQ1 的调节关系。结果显示，DUXAP8/microRNA-378a-3p/FOXQ1的表达对结肠癌细胞功能有影响：结果表明：结肠癌组织中 DUXAP8 和 FOXQ1 的表达上调，而 microRNA-378a-3p 的表达下调。DUXAP8表达的增加与淋巴结转移和TNM分期呈正相关。双荧光素酶和RNA免疫沉淀实验表明，DUXAP8是microRNA-378a-3p的海绵，并能靶向调节microRNA-378a-3p调节FOXQ1的能力。此外，功能实验结果显示，过表达 DUXAP8 能促进结肠癌细胞的生长和迁移能力。DUXAP8还能逆转microRNA-378a-3p的抑瘤作用。然而，沉默FOXQ1可以逆转DUXAP8高表达的促癌作用：结论：DUXAP8在结肠癌中的表达明显增加，这与淋巴结转移和结肠癌患者的不良预后有关。DUXAP8可能通过影响microRNA-378a-3p/FOXQ1加速结肠癌细胞的恶性进展。

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来源期刊

Gut and Liver 医学-胃肠肝病学

CiteScore

7.50

自引率

8.80%

发文量

119

审稿时长

6-12 weeks

期刊介绍： Gut and Liver is an international journal of gastroenterology, focusing on the gastrointestinal tract, liver, biliary tree, pancreas, motility, and neurogastroenterology. Gut and Liver delivers up-to-date, authoritative papers on both clinical and research-based topics in gastroenterology. The Journal publishes original articles, case reports, brief communications, letters to the editor and invited review articles in the field of gastroenterology. The Journal is operated by internationally renowned editorial boards and designed to provide a global opportunity to promote academic developments in the field of gastroenterology and hepatology. Gut and Liver is jointly owned and operated by 8 affiliated societies in the field of gastroenterology, namely: the Korean Society of Gastroenterology, the Korean Society of Gastrointestinal Endoscopy, the Korean Society of Neurogastroenterology and Motility, the Korean College of Helicobacter and Upper Gastrointestinal Research, the Korean Association for the Study of Intestinal Diseases, the Korean Association for the Study of the Liver, the Korean Pancreatobiliary Association, and the Korean Society of Gastrointestinal Cancer.