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长链非编码RNA DPP10-AS1通过调控微小RNA-127-3p上调腺苷酸环化酶1,从而对结肠癌发挥抗肿瘤作用。

Long non-coding RNA DPP10-AS1 exerts anti-tumor effects on colon cancer the upregulation of ADCY1 by regulating microRNA-127-3p.

作者信息

Liu Gang, Zhao Hui, Song Qiang, Li Guangmeng, Lin Shuying, Xiong Sheng

机构信息

Institute of Biomedicine and National Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, P. R. China.

Central Laboratory, Chongqing Three Gorges Central Hospital, Chongqing 404000, P. R. China.

出版信息

Aging (Albany NY). 2021 Mar 19;13(7):9748-9765. doi: 10.18632/aging.202729.

Abstract

Herein we hypothesized that DPP10-AS1 could affect the development of colon cancer via the interaction with miR-127-3p and adenylate cyclase 1 (ADCY1). After sorting of CD133 positive cells, sphere formation, colony formation, proliferation, invasion, migration, and apoptosis were detected to explore the involvement of DPP10-AS1 and miR-127-3p in the colon cancer stem cell (CCSC) properties through gain- and loss-of function approaches. Furthermore, tumor xenograft in nude mice was conducted to investigate the effect of DPP10-AS1 and miR-127-3p on tumor growth . Poorly expressed DPP10-AS1 and ADCY1, while highly expressed miR-127-3p were found in CCSCs. Low expression of DPP10-AS1 was correlated with TNM stage, lymphatic node metastasis, and tumor differentiation. Upregulation of DPP10-AS1 increased ADCY1 protein expression, decreased the protein expression of CCSC-related factors, inhibited sphere formation, colony formation, proliferation, invasion and migration, and accelerated apoptosis of HT-29 and SW480 cells by suppressing the expression of miR-127-3p. Further, the above findings were also confirmed by assays. Taken together, this study demonstrates that DPP10-AS1 inhibits CCSC proliferation by regulating miR-127-3p and ADCY1, providing fresh insight into a promising novel treatment strategy for colon cancer.

摘要

在此,我们假设DPP10-AS1可能通过与miR-127-3p和腺苷酸环化酶1(ADCY1)相互作用来影响结肠癌的发展。在分选CD133阳性细胞后,通过功能获得和功能缺失方法检测成球、集落形成、增殖、侵袭、迁移和凋亡,以探讨DPP10-AS1和miR-127-3p在结肠癌干细胞(CCSC)特性中的作用。此外,进行裸鼠肿瘤异种移植以研究DPP10-AS1和miR-127-3p对肿瘤生长的影响。在CCSCs中发现DPP10-AS1和ADCY1表达较低,而miR-127-3p表达较高。DPP10-AS1低表达与TNM分期、淋巴结转移和肿瘤分化相关。上调DPP10-AS1可增加ADCY1蛋白表达,降低CCSC相关因子的蛋白表达,抑制HT-29和SW480细胞的成球、集落形成、增殖、侵袭和迁移,并通过抑制miR-127-3p的表达加速细胞凋亡。此外,上述结果也通过实验得到证实。综上所述,本研究表明DPP10-AS1通过调节miR-127-3p和ADCY1抑制CCSC增殖,为结肠癌提供了一种有前景的新治疗策略的新见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f909/8064199/b7efc621ed7f/aging-13-202729-g001.jpg

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