Gastrin-related circRNA_0017065 promotes the proliferation and metastasis of colorectal cancer through the miR-3174/RBFOX2 axis.

IF 5.7 2区 生物学 Q1 BIOLOGY Biology Direct Pub Date : 2024-08-29 DOI:10.1186/s13062-024-00509-7
Xu Wang, Tianjiao Sun, Jiapeng Fan, Xueliang Zuo, Jiading Mao
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Abstract

Gastrin is a gastrointestinal peptide hormone that plays an important role in the progression of colorectal cancer (CRC). However, the molecular mechanism remains unclear. In this study, we identified gastrin-related circRNAs via high-throughput sequencing and selected circRNA_0017065 as the research focus. We further studied its specific role and molecular mechanism in the progression of CRC. Knockdown and overexpression of circRNA_0017065 were performed, and the biological function of circRNA_0017065 in CRC progression was studied via in vitro and in vivo functional experiments. The potential downstream target genes were subsequently identified via screening of databases and gene chip data. The expression of circRNA_0017065 in tumour tissues was significantly upregulated compared with that in adjacent normal tissues. In vitro and in vivo functional experiments revealed that the proliferation and migration of CRC cells were significantly suppressed after circRNA_0017065 knockdown, while apoptosis was promoted. After overexpression of circRNA_0017065, the proliferation and migration of CRC cells were significantly promoted, while apoptosis was inhibited. Mechanistic studies revealed that circRNA_0017065 can act as a sponge for miR-3174 and promote CRC progression via the miR-3174/RBFOX2 axis. In general, gastrin-related circRNA_0017065 plays a key role in the occurrence and development of CRC and is expected to be a potential molecular target for the treatment of CRC metastasis.

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胃泌素相关circRNA_0017065通过miR-3174/RBFOX2轴促进结直肠癌的增殖和转移
胃泌素是一种胃肠道肽类激素,在结直肠癌(CRC)的进展过程中发挥着重要作用。然而,其分子机制仍不清楚。在这项研究中,我们通过高通量测序鉴定了胃泌素相关的 circRNA,并选择 circRNA_0017065 作为研究重点。我们进一步研究了它在 CRC 进展中的特殊作用和分子机制。我们对circRNA_0017065进行了敲除和过表达,并通过体外和体内功能实验研究了circRNA_0017065在CRC进展中的生物学功能。随后,通过数据库和基因芯片数据的筛选,确定了潜在的下游靶基因。与邻近正常组织相比,circRNA_0017065在肿瘤组织中的表达明显上调。体外和体内功能实验显示,circRNA_0017065敲除后,CRC细胞的增殖和迁移明显受到抑制,同时促进了细胞凋亡。过表达circRNA_0017065后,CRC细胞的增殖和迁移被明显促进,而细胞凋亡受到抑制。机理研究发现,circRNA_0017065可作为miR-3174的海绵,通过miR-3174/RBFOX2轴促进CRC的进展。总之,胃泌素相关的circRNA_0017065在CRC的发生和发展中起着关键作用,有望成为治疗CRC转移的潜在分子靶点。
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来源期刊
Biology Direct
Biology Direct 生物-生物学
CiteScore
6.40
自引率
10.90%
发文量
32
审稿时长
7 months
期刊介绍: Biology Direct serves the life science research community as an open access, peer-reviewed online journal, providing authors and readers with an alternative to the traditional model of peer review. Biology Direct considers original research articles, hypotheses, comments, discovery notes and reviews in subject areas currently identified as those most conducive to the open review approach, primarily those with a significant non-experimental component.
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