KIAA1429 regulates the migration and invasion of hepatocellular carcinoma by altering m6A modification of ID2 mRNA
KIAA1429 regulates the migration and invasion of hepatocellular carcinoma by altering m6A modification of ID2 mRNA
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DOI：
10.2147/ott.s180954
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发表时间：
2019-01-01
影响因子：
4
通讯作者：
Huang, Guanjun
中科院分区：
文献类型：
--
作者：
Cheng, Xiaoyu;Li, Ming;Huang, Guanjun
目的：N6-甲基腺苷（m6 A）是哺乳动物中最丰富的mRNA修饰，参与多种生物学过程。KIAA 1429是参与m6 A修饰的重要甲基转移酶。然而，KIAA 1429在肝细胞癌（HCC）中的作用仍然没有很好地理解。本研究旨在探讨KIAA 1429在HCC中的功能及其调控机制。患者与方法：通过癌症基因组图谱（TCGA）数据库中HCC患者的临床和表达数据，对HCC相关基因进行分析。通过定量逆转录PCR验证KIAA 1429的表达，并使用小干扰RNA（siRNA）获得干扰效率。结果：KIAA 1429基因在HCC组织中的表达与正常肝组织相比存在差异。比较HCC细胞系（HepG 2、Huh-7、HepG2.2.15）与正常肝细胞（HL-7702），我们观察到KIAA 1429表达的相同显著差异。KIAA 1429显著增强HepG 2细胞的增殖、迁移和侵袭。此外，京都基因和基因组百科全书功能富集分析和相关性分析显示KIAA 1429和ID 2之间存在显著的负相关性。结论：KIAA 1429通过上调ID 2 mRNA的m6 A修饰，抑制ID 2的表达，从而促进肝癌细胞的迁移和侵袭。
Purpose: N6-methyladenosine (m6A), the most abundant mRNA modification in mammals, is involved in various biological processes. KIAA1429 is an important methyltransferase participating in m6A modification. However, the role of KIAA1429 in hepatocellular carcinoma (HCC) is still not well understood. Here, we aimed to investigate the function of KIAA1429 and its corresponding regulation mechanisms in HCC.Patients and methods: HCC-related genes were analyzed by clinical and expression data of HCC patients in The Cancer Genome Atlas (TCGA) database. Expression of KIAA1429 was verified by quantitative reverse-transcription PCR, and interference efficiency was obtained using small interfering RNA (siRNA). Cell proliferation, migration, and invasion were assessed by cell counting kit-8 and transwell assays, and the m6A modification was detected by methylated RNA immunoprecipitation-PCR (MeRIP-PCR).Results: We found a difference in the expression of KIAA1429 between HCC and normal hepatic tissues by analyzing data from the TCGA database. Comparing HCC cell lines (HepG2, Huh-7, HepG2.2.15) with normal hepatic cells (HL-7702), we observed an identically significant difference in KIAA1429 expression. KIAA1429 significantly enhanced proliferation, migration, and invasion of HepG2 cells. Moreover, Kyoto Encyclopedia of Genes and Genomes functional enrichment analysis and correlation analysis revealed a significant negative correlation between KIAA1429 and ID2. In the subsequent MeRIP-PCR assay, downregulation of KIAA1429 inhibited m6A modification of ID2 mRNA.Conclusion: KIAA1429 facilitated migration and invasion of HCC by inhibiting ID2 via upregulating m6A modification of ID2 mRNA.