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摘要：
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摘要：目的 探讨2型糖尿病（type 2 diabetes mellitus，T2DM）合并代谢相关脂肪性
肝病（metabolic associated fatty liver disease，MAFLD）中环状RNA（circular RNA，
circRNA）的分子调控机制。方法 选取2020年12月15日至2021年12月15日于新疆医
科大学第六附属医院就诊的18例T2DM患者和18例T2DM合并MAFLD患者为T2DM
组和T2DM合并MAFLD组，另选取同期18例年龄和性别匹配的健康人群为健康对照
组。留取所有研究对象的外周血单核细胞样本。每组随机选择3例进行转录组测序并
筛选显著差异表达的mRNA（differentially expressed mRNA，DEmRNA）和circRNA
（differentially expressed circRNA，DEcircRNA），对DEmRNA进行基因本体（gene
ontology，GO）和KEGG通路富集分析。构建circRNAs/miRNA/mRNA的内源竞争RNA
（competing endogenous RNA，ceRNA）调控网络。采用反转录定量聚合酶链式反应
（reverse transcription quantitative polymerase chain reaction，RT-qPCR）验证关键基因（hascirc0035198）
在所有样本中的表达水平。结果 与健康对照组比较，T2DM合并MAFLD组
中发现478个共同的DEmRNA和11个共同的DEcircRNA。DEmRNA主要参与黏着斑、Wnt
信号通路和cGMP-PKG信号通路等。has-circ0035198/hsa-miR-3173-3p/CSNK2A1的ceRNA
网络参与Wnt信号通路。RT-qPCR检测表明has-circ0035198在T2DM合并MAFLD患者的
表达水平（0.589 ± 0.199）均显著低于T2DM组（0.872 ± 0.28）和对照组（1.09 ± 0.443）
（t值分别为3.191、3.995，P值分别为0.004、＜ 0.001）。 结论 has-circ0035198/hsa-miR-
3173-3p/CSNK2A1可能通过Wnt通路参与T2DM合并MAFLD的发病机制。
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Abstract: Objective To investigate the molecular regulatory mechanisms of circular RNA
(circRNA) in type 2 diabetes mellitus (T2DM) complicated with metabolism associated fatty
liver disease (MAFLD). Methods Total of 18 cases with T2DM and 18 cases with T2DM
and MAFLD in the Sixth Affiliated Hospital of Xinjiang Medical University from December
2020 to December 2022 were selected as T2DM group and T2DM complicated with MAFLD
group, respectively. Additionally, 18 age- and gender- matched healthy individuals were selected
as the healthy control group. Peripheral blood mononuclear cell samples were collected from
all participants. For transcriptome sequencing, 3 cases were randomly selected from each group
to identify significantly and differentially expressed mRNA (DEmRNA) and differentially
expressed circRNA (DEcircRNA). DEmRNA were subjected to gene ontology (GO) enrichment
analysis and KEGG pathway enrichment analysis. Competing endogenous RNA (ceRNA)
regulatory network involving circRNAs/miRNA/mRNA was constructed. Reverse transcription
quantitative polymerase chain reaction (RT-qPCR) was used to verify the expression level of the
key gene (has-circ0035198) in all samples. Results Compared with the healthy control group,
478 common DEmRNA and 11 common DEcircRNA were identified in T2DM complicated
with MAFLD group. DEmRNA were mainly involved in focal adhesion, Wnt signaling pathway
and cGMP-PKG signaling pathway. The ceRNA network of has-circ0035198/hsa-miR-3173-
3p/CSNK2A1 was involved in the Wnt signaling pathway. RT-qPCR detection showed that
the expression level of has-circ0035198 in patients with T2DM complicated with MAFLD
(0.589 ± 0.199) was significantly lower than that of the T2DM group (0.872 ± 0.28) and healthy
control group (1.09 ± 0.443) (t values were 3.191 and 3.995, P values were 0.004 and ＜ 0.001,
respectively). Conclusion Has-circ0035198 / hsa-miR-3173-3p/CSNK2A1 may be involved in
the pathomechanism of T2DM with MAFLD through the Wnt pathway.
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