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长链非编码RNA HAND2-AS1通过调控miR-3118/ZG16轴抑制结肠癌进展。

LncRNA HAND2-AS1 Inhibited Colon Cancer Progression By Regulating miR-3118/ZG16 Axis.

作者信息

Hu Ling, Xie Linfeng, Huang Shan, Li Qiu

机构信息

Department of Gastroenterology, WUHAN ASIA GENERAL HOSPITAI, Wuhan, 430050, Hubei, China.

Department of Anus and Intestine Surgery, Clinical Medical College &, Affiliated Hospital of Chengdu University, Chengdu, 610081, Sichuan, China.

出版信息

Biochem Genet. 2024 Sep 14. doi: 10.1007/s10528-024-10905-3.

Abstract

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.

摘要

长链非编码RNA HAND2-AS1是一种新型癌症调节因子,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楚HAND2-AS1如何调节CC的进展。我们使用qRT-PCR研究了CC组织和细胞中miR-3118、HAND2-AS1和ZG16的表达水平。通过蛋白质免疫印迹法定量凋亡相关蛋白(Bax和Bcl-2)和ZG16的蛋白质水平。体外功能分析涉及蛋白质免疫印迹法、伤口愈合试验和CCK-8。使用荧光素酶报告基因和RNA免疫沉淀试验研究miR-3118、HAND2-AS1和ZG16之间的结合关系。使用体内异种移植肿瘤模型分析HAND2-AS1的功能作用。在CC的组织和细胞中,HAND2-AS1表达下调。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,它会减少体内CC肿瘤的发展。在CC细胞和组织中,miR-3118与HAND2-AS1竞争并升高。此外,还注意到HAND2-AS1过表达时会降低CC细胞的存活率,然而miR-3118过表达可恢复这些变化。ZG16被证明是miR-3118的靶标,发现ZG16在CC组织和细胞中表达下调。我们观察到,ZG16的高表达部分恢复了由miR-3118过表达引起的增强的恶性表型。HAND2-AS1通过海绵吸附miR-3118上调ZG16表达,从而抑制CC进展。因此,HAND2-AS1/miR-3118/ZG16轴可能是CC治疗的一个新靶点。

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