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综合性多组学方法识别了结直肠癌中新型竞争性内源性RNA (ceRNA) 网络

Ghanbar Mahmoodi Chalbatani¹, Elahe Gharagouzloo^1,2, Mohammad Amin Malekraeisi³

¹Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Science, Tehran, Iran.

Scientific reports

|November 9, 2023

概括

循环RNAs (circRNAs) 在结直肠癌 (CRC) 中充当竞争的内源RNAs (ceRNAs). 这项研究确定了hsa_circ_000240作为一个关键的circRNA,透露了它在CRC进展中的作用,通过与CDC6和ORC1等特定基因的相互作用,提供了潜在的治疗点.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
基因组学就是基因组学.

背景情况:

循环RNAs (circRNAs) 是通过涉及microRNAs (miRNAs) 的竞争性内源RNA (ceRNA) 机制在癌症中被公认的调节者.
在结直肠癌 (CRC) 病原发生过程中,circ000240,其miRNA相互作用和mRNA点的具体作用尚不清楚.

研究的目的:

为了阐明hsa_circ_000240/miRNA/mRNA轴在结直肠癌 (CRC) 中的病理功能.
确定参与CRC进展的关键基因和调控途径,以及它们与患者存活率和免疫细胞透的关联.

主要方法:

定量实时PCR (qRT-PCR) 用于评估hsa_circ_000240在CRC组织中的表达.
生物信息分析包括网络拓,微阵列,散装RNA测序和单细胞RNA测序 (scRNA-seq) 以确定miRNA-mRNA相互作用和枢纽基因.
ATAC-seq和甲基化分析,以调查与候选基因相关的表观遗传修饰.

主要成果:

在CRC组织中,hsa_circ_000240被显著上调.
鉴定了三个相互作用的miRNA和1680个下游目标基因,网络分析确定了33个枢纽基因,包括CDC6和ORC1,这显著影响了整体存活率.
scRNA-seq和ATAC-seq证实CRC中CDC6和ORC1的表达升高,与免疫细胞透,染色质可访问性以及诸如基因素乙化和促进物甲基化等表观遗传修饰有关.

结论:

hsa_circ_000240 作为CRC中的ceRNA功能,通过CDC6和ORC1轴影响癌症的进展.
这些发现突出了新的表观遗传调节机制,并确定了CDC6和ORC1作为CRC免疫治疗的潜在治疗点.

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