miR-378a-5p靶向GABPα抑制结直肠癌的生长和血管生成。

IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY International Journal of Biochemistry & Cell Biology Pub Date : 2025-02-01 DOI:10.1016/j.biocel.2024.106729
Mengyi Wang , Jiangfa Qi , Zhenlin Tan , Runlong Zhou , Qing Zhuo , Xiaotong Deng , Zhenrong Wang , Ruijie Zhou , Fan Li , Yao Xu
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引用次数: 0

摘要

考虑到结直肠癌的恶性程度高、复发率高、预后差,探索有前景的靶点是结直肠癌治疗的迫切策略。最近的研究表明,GABPα在癌症侵袭性中起作用,但其在结直肠癌进展中的确切功能和调节机制尚不清楚。本研究旨在探讨GABPα及其上游调节因子miR-378a-5p在调节癌症进展中的生物学作用。通过综合数据挖掘和qPCR分析GABPα和miR-378a-5p的表达水平。采用CCK-8法、创面愈合法、跨井侵入法、成管法和裸鼠异种移植模型评价GABPα的功能作用。我们还进行了共转染实验来研究miR-378a-5p和GABPα之间的调控关系。我们发现GABPα在人结直肠癌组织和细胞系中表达显著下调。功能实验显示,GABPα过表达可抑制结直肠癌细胞的增殖、迁移、侵袭和血管生成,体内实验进一步证实了GABPα的抑制作用。此外,miR-378a-5p在结直肠癌中表达上调,GABPα被确定为miR-378a-5p的直接靶点,荧光素酶报告基因检测证实了这一点。此外,GABPα的过表达部分抵消了miR-378a-5p诱导的癌细胞恶性行为的增强。我们的研究结果表明,miR-378a-5p通过直接靶向GABPα促进结直肠癌的侵袭性进展,突出了这一调节轴作为结直肠癌的潜在治疗靶点。
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GABPα targeted by miR-378a-5p inhibits the growth and angiogenesis of colorectal carcinoma
Considering the high degree of malignancy, recurrence rate and poor prognosis, exploring promising targets is an imperious strategy for colorectal carcinoma therapy. Recent studies have indicated that GABPα plays a role in cancer aggressiveness, but its exact function and regulatory mechanisms in colorectal cancer progression remain unclear. This study aims to explore the biological role of GABPα and its upstream regulator, miR-378a-5p, in modulating cancer progression. The expression levels of GABPα and miR-378a-5p were analyzed through comprehensive data mining and qPCR assays. The functional effects of GABPα were assessed using CCK-8, wound healing, transwell invasion assay, tube formation and xenograft model in nude mice. A co-transfection assay was also performed to investigate the regulatory relationship between miR-378a-5p and GABPα. We found that GABPα expression was significantly downregulated in human colorectal cancer tissues and cell lines. Functional assays revealed that GABPα overexpression suppressed the proliferation, migration, invasion and angiogenesis of colorectal cancer cells, and in vivo experiments further confirmed the inhibitory role of GABPα. Additionally, miR-378a-5p was upregulated in colorectal cancer, and GABPα was identified as a direct target of miR-378a-5p, as confirmed by luciferase reporter assays. Furthermore, overexpression of GABPα partially counteracted the enhanced malignant behaviors of cancer cells induced by miR-378a-5p. Our findings suggest that miR-378a-5p promotes the aggressive progression of colorectal cancer by directly targeting GABPα, highlighting this regulatory axis as a potential therapeutic target for colorectal carcinoma.
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来源期刊
CiteScore
8.10
自引率
0.00%
发文量
124
审稿时长
19 days
期刊介绍: IJBCB publishes original research articles, invited reviews and in-focus articles in all areas of cell and molecular biology and biomedical research. Topics of interest include, but are not limited to: -Mechanistic studies of cells, cell organelles, sub-cellular molecular pathways and metabolism -Novel insights into disease pathogenesis -Nanotechnology with implication to biological and medical processes -Genomics and bioinformatics
期刊最新文献
Identification of a liver fibrosis and disease progression-related transcriptome signature in non-alcoholic fatty liver disease Editorial Board 5'tiRNA-33-CysACA-1 promotes septic cardiomyopathy by targeting PGC-1α-mediated mitochondrial biogenesis Prevention of fenitrothion induced hepatic toxicity by saponarin via modulating TLR4/MYD88, JAK1/STAT3 and NF-κB signaling pathways Corrigendum to “Dimerization of ZIP promotes its transcriptional repressive function and biological activity” [Int. J. Biochem. Cell Biol. 44 (2012) 886–895]
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