HAND2-AS1 plays a tumor-suppressive role in hepatoblastoma through the negative regulation of CDK1

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作者：Keke Chen, Yalan You, Wenfang Tang, Xin Tian, Chengguang Zhu, Zexi Yin, Minhui Zeng, Xiangling He
期刊：Heliyon
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Objective
Hepatoblastoma (HB) is the most commonly seen pediatric liver malignancy. The preliminary experiment of our research group found that cyclin dependent kinase 1 (CDK1) was upregulated in HB. By in silico analysis, long noncoding RNA (lncRNA) HAND2 antisense RNA 1 (HAND2-AS1) was determined as the research object. Herein, HAND2-AS1 expression in HB and its effect and mechanism on HB were extensively investigated.
Methods
CDK1-related lncRNAs were searched using the microarray data from the Gene Expression Omnibus (GEO) database and Gene Expression Profiling Interactive Analysis (GEPIA) online database. qRT-PCR, Western blot, and immunohistochemistry were performed to determine the mRNA expression and protein levels of target genes. MTT, flow cytometry and DAPI staining assays were conducted to measure proliferation activity, cell cycle progression, and apoptosis of HB cells. The interaction between lncRNA and protein was determined by RNA pull-down and FISH assays. Luciferase assay was applied to identify whether HAND2-AS1 stimulates the transcription of CDK1. CDK1 mRNA stability was detected through actinomycin D assay. Aycloheximide assay was used to detect the CDK1 protein stability.
Results
HAND2-AS1 was downregulated in HB tissues and cells. HAND2-AS1 overexpression impeded HB cells proliferation activity and cycle progression while inducing cell apoptosis of HB cells, while knockdown of HAND2-AS1 emerged the opposite effect. HAND2-AS1 negatively correlated with CDK1. HAND2-AS1 downregulated CDK1 expression by affecting the transcriptional activity, mRNA and protein stability of CDK1. Furthermore, HAND2-AS1 impeded HB cell proliferation and cycle progression while inducing cell apoptosis by downregulating CDK1.
Conclusion
Our research highlights that HAND2-AS1 can exert a tumor-suppressive effect on HB through the negative regulation of CDK1, and the HAND2-AS1/CDK1 is expected to be a diagnostic molecular marker and therapeutic target for HB in clinical practice.