LncRNA HAND2-AS1 通过调控 miR-3118/ZG16 轴抑制结肠癌进展

IF 2.1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochemical Genetics Pub Date : 2024-09-14 DOI:10.1007/s10528-024-10905-3
Ling Hu, Linfeng Xie, Shan Huang, Qiu Li
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引用次数: 0

摘要

LncRNA HAND2-AS1是一种新型癌症调控因子,但HAND2-AS1在结肠癌(CC)进展中的作用和机制仍不清楚。本研究的目的是弄清HAND2-AS1如何调控CC的进展。通过 qRT-PCR,我们研究了 miR-3118、HAND2-AS1 和 ZG16 在 CC 组织和细胞中的表达水平。蛋白水平(Bax和Bcl-2)和ZG16通过Western印迹进行定量。体外功能分析参考了 Western 印迹、伤口愈合试验和 CCK-8。利用荧光素酶报告和 RIP 试验研究了 miR-3118、HAND2-AS1 和 ZG16 之间的结合关系。利用体内异种移植肿瘤模型分析了HAND2-AS1的功能作用。在CC的组织和细胞中,HAND2-AS1被下调。我们观察到,HAND2-AS1过表达会降低CC细胞的增殖和迁移,同时促进细胞凋亡。我们进一步证实,当HAND2-AS1过表达时,会减少CC肿瘤在体内的发展。在CC细胞和组织中,miR-3118与HAND2-AS1竞争并升高。此外,研究还发现,HAND2-AS1过表达会降低CC细胞的存活率,而miR-3118的过表达则会恢复这些变化。ZG16被证明是miR-3118的靶标,研究发现ZG16在CC组织和细胞中被下调。我们观察到,ZG16的高表达部分恢复了miR-3118过表达导致的恶性表型增强。HAND2-AS1通过疏导miR-3118,上调ZG16的表达,从而抑制了CC的进展。因此,HAND2-AS1/miR-3118/ZG16轴可能是治疗CC的新靶点。
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LncRNA HAND2-AS1 Inhibited Colon Cancer Progression By Regulating miR-3118/ZG16 Axis

LncRNA HAND2-AS1 is a novel cancer regulator, but the role and mechanisms of HAND2-AS1 involved with colon cancer (CC) progression remains unknown. The purpose of this research was to figure out how HAND2-AS1 regulates the progression of CC. Using qRT-PCR, we studied expression levels of miR-3118, HAND2-AS1, and ZG16 in CC tissues and cells. Protein levels of apoptosis-related proteins (Bax and Bcl-2) and ZG16 were quantified by western blotting. In vitro function analysis referred to western blotting, wound healing assay and CCK-8. The binding association among miR-3118, HAND2-AS1, and ZG16 was investigated using luciferase reporter and RIP assays. The functional role of HAND2-AS1 was analyzed using xenograft tumor models in vivo. In tissues and cells of CC, HAND2-AS1 was downregulated. We observed that HAND2-AS1 overexpression declined CC cell proliferation and migration while facilitating apoptosis. We further verified that when HAND2-AS1 is overexpressed it reduced CC tumor development in vivo. In CC cells and tissues, miR-3118 competed with HAND2-AS1 and was elevated. Further it was noted that the HAND2-AS1 when overexpressed, lessened the survival of CC cells, however overexpression of miR-3118 restored these changes. ZG16 was shown to be a target of miR-3118, it was found that ZG16 was downregulated in CC tissue and cells. We observed, high expression of ZG16 partially restored the enhanced malignant phenotype caused by miR-3118 overexpression. HAND2-AS1 inhibited CC progression by upregulating ZG16 expression through sponging miR-3118. Hence, HAND2-AS1/miR-3118/ZG16 axis could be a possible new target for CC treatment.

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来源期刊
Biochemical Genetics
Biochemical Genetics 生物-生化与分子生物学
CiteScore
3.90
自引率
0.00%
发文量
133
审稿时长
4.8 months
期刊介绍: Biochemical Genetics welcomes original manuscripts that address and test clear scientific hypotheses, are directed to a broad scientific audience, and clearly contribute to the advancement of the field through the use of sound sampling or experimental design, reliable analytical methodologies and robust statistical analyses. Although studies focusing on particular regions and target organisms are welcome, it is not the journal’s goal to publish essentially descriptive studies that provide results with narrow applicability, or are based on very small samples or pseudoreplication. Rather, Biochemical Genetics welcomes review articles that go beyond summarizing previous publications and create added value through the systematic analysis and critique of the current state of knowledge or by conducting meta-analyses. Methodological articles are also within the scope of Biological Genetics, particularly when new laboratory techniques or computational approaches are fully described and thoroughly compared with the existing benchmark methods. Biochemical Genetics welcomes articles on the following topics: Genomics; Proteomics; Population genetics; Phylogenetics; Metagenomics; Microbial genetics; Genetics and evolution of wild and cultivated plants; Animal genetics and evolution; Human genetics and evolution; Genetic disorders; Genetic markers of diseases; Gene technology and therapy; Experimental and analytical methods; Statistical and computational methods.
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