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通过直接靶向miR-431/LASP1轴鉴定环状RNA circ-CSPP1为结直肠癌的有效驱动因子。

Identification of circRNA circ-CSPP1 as a potent driver of colorectal cancer by directly targeting the miR-431/LASP1 axis.

作者信息

Li Minghao, Zhuang Jianbin, Kang Di, Chen Yuzhuo, Song Weiliang

机构信息

Department of Gastrointestinal Anorectal Surgery, Tianjin Third Central Hospital, No. 83, Jintang Road, Hedong District, Tianjin, 300170, China.

出版信息

Open Life Sci. 2021 May 29;16(1):523-536. doi: 10.1515/biol-2021-0053. eCollection 2021.

Abstract

Colorectal cancer (CRC) is the third most common malignancy worldwide. Circular RNAs (circRNAs) have been implicated in cancer biology. The purpose of the current work is to investigate the precise parts of circRNA centrosome and spindle pole-associated protein 1 (circ-CSPP1) in the progression of CRC. Our data showed that circ-CSPP1 was significantly overexpressed in CRC tissues and cells. The knockdown of circ-CSPP1 attenuated cell proliferation, migration, invasion and promoted apoptosis and weakened tumor growth . circ-CSPP1 directly targeted miR-431, and circ-CSPP1 knockdown modulated CRC cell progression via upregulating miR-431. Moreover, LIM and SH3 protein 1 (LASP1) was a functional target of miR-431 in modulating CRC cell malignant progression. Furthermore, circ-CSPP1 in CRC cells functioned as a posttranscriptional regulator on LASP1 expression by targeting miR-431. Our present study identified the oncogenic role of circ-CSPP1 in CRC partially by the modulation of the miR-431/LASP1 axis, providing evidence for circ-CSPP1 as a promising biomarker for CRC management.

摘要

结直肠癌(CRC)是全球第三大常见恶性肿瘤。环状RNA(circRNAs)与癌症生物学有关。当前研究的目的是探究环状RNA中心体和纺锤极相关蛋白1(circ-CSPP1)在结直肠癌进展中的具体作用。我们的数据表明,circ-CSPP1在结直肠癌组织和细胞中显著过表达。敲低circ-CSPP1可减弱细胞增殖、迁移、侵袭并促进细胞凋亡,还能抑制肿瘤生长。circ-CSPP1直接靶向miR-431,敲低circ-CSPP1可通过上调miR-431来调节结直肠癌细胞的进展。此外,LIM和SH3结构域蛋白1(LASP1)是miR-431调节结直肠癌细胞恶性进展的功能靶点。此外,结直肠癌细胞中的circ-CSPP1通过靶向miR-431对LASP1表达发挥转录后调节作用。我们目前的研究部分通过miR-431/LASP1轴的调节确定了circ-CSPP1在结直肠癌中的致癌作用,为circ-CSPP1作为结直肠癌治疗的有前景的生物标志物提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b99/8165258/61a117281937/j_biol-2021-0053-fig001.jpg

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