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The lncRNA KIF9-AS1 Accelerates Hepatocellular Carcinoma Growth by Recruiting DNMT1 to Promote RAI2 DNA Methylation

BACKGROUND: Hepatocellular carcinoma (HCC) is a very common malignant tumor. Long noncoding RNAs (lncRNAs) enable discoveries of new therapeutic tumor targets. We aimed to study the role and potential regulatory mechanisms of the lncRNA KIF9-AS1 in HCC. METHODS: CCK-8, scratch assay, and flow cytome...

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Detalles Bibliográficos
Autores principales: Yu, Yong, Lu, Xianghong, Yan, Yang, Wang, Yonggang, Meng, Jiangyun, Tian, Shufeng, Mu, Jinsong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9584731/
https://www.ncbi.nlm.nih.gov/pubmed/36276278
http://dx.doi.org/10.1155/2022/3888798
Descripción
Sumario:BACKGROUND: Hepatocellular carcinoma (HCC) is a very common malignant tumor. Long noncoding RNAs (lncRNAs) enable discoveries of new therapeutic tumor targets. We aimed to study the role and potential regulatory mechanisms of the lncRNA KIF9-AS1 in HCC. METHODS: CCK-8, scratch assay, and flow cytometry were used to detect cell proliferation, migration, and apoptosis, respectively. Bax, Bcl-2, ERK, and pERK expression were measured by western blotting. StarBase predicted KIF9-AS1 expression in HCC and paracancerous tissues. RPISeq predicted the interaction score of KIF9-AS1 and DNMT1, and MethyPrimer revealed the CpG island distribution in the RAI2 promoter. MSP was performed to measure RAI2 methylation. RIP and ChIP were performed to examine lncRNA KIF9-AS1, DNMT1, and RAI2 interactions. Finally, the effect of KIF9-AS1 knockdown on HCC was verified with nude mice. RESULTS: We found that KIF9-AS1 expression was increased in HCC tissues. KIF9-AS1 knockdown inhibited the proliferation and migration, and facilitated the apoptosis of HCC cells. lncRNA KIF9-AS1-mediated RAI2 expression led to DNMT1 recruitment and regulated RAI2 DNA methylation. RAI2 overexpression inhibited the proliferation and migration and promoted the apoptosis of HCC cells. KIF9-AS1 knockdown inhibited subcutaneous tumor formation in vivo. CONCLUSION: This study shows that KIF9-AS1 accelerates HCC growth by inducing DNMT1 promotion of RAI2 DNA methylation.