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Background

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated mortality worldwide. CircZKSCAN1 (hsa_circ_0001727) was reported to be related to HCC development. The present study aims to elucidate the potential role and molecular mechanism of circZKSCAN1 in the regulation of HCC progression.

Methods

CircZKSCAN1, miR-873-5p, and downregulation of deleted in liver cancer 1 (DLC1) in HCC tissues and cells were detected by RT-qPCR. Correlation between circZKSCAN1 expression and overall survival rate was measured by Kaplan-Meier survival analysis. The effects of circZKSCAN1, miR-873-5p, and DLC1 on proliferation, migration, and invasion were analyzed by CCK-8 and transwell assays, respectively. CyclinD1, Matrix metalloproteinase (MMP)-9, MMP-2, and DLC1 in HCC cells were detected by Western blot assay. The binding relationship between miR-873-5p and circZKSCAN1 or DLC1 was predicted by the Circinteractome or Starbase, and then confirmed by dual-luciferase reporter assays, respectively. Tumor volume and tumor weight were measured in vivo.

Results

CircZKSCAN1 was downregulated in HCC tissues and cells. Kaplan-Meier survival analysis suggested that there was a positive correlation between circZKSCAN1 expression and overall survival rate. Functionally, circZKSCAN1 blocked proliferation, migration, and invasion of HCC cells. MiR-873-5p was a target miRNA of circZKSCAN1, and miR-873-5p directly bound with DLC1. Rescue experiments confirmed that miR-873-5p overexpression or DLC1 knockdown attenuated the suppressive effects of circZKSCAN1 on HCC tumor growth in vitro. Besides, circZKSCAN1 inhibited HCC cell growth in vivo.

Conclusions

This study firstly revealed that circZKSCAN1 curbed HCC progression via modulating miR-873-5p/DLC1 axis, providing a potential therapeutic target for HCC treatment."xsd:string
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http://purl.uniprot.org/citations/33439397http://purl.uniprot.org/core/author"Wang L."xsd:string
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http://purl.uniprot.org/citations/33439397http://purl.uniprot.org/core/name"Dig Dis Sci"xsd:string
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http://purl.uniprot.org/citations/33439397http://purl.uniprot.org/core/title"CircZKSCAN1 Suppresses Hepatocellular Carcinoma Tumorigenesis by Regulating miR-873-5p/Downregulation of Deleted in Liver Cancer 1."xsd:string
http://purl.uniprot.org/citations/33439397http://purl.uniprot.org/core/volume"66"xsd:string
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