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KMID : 0381120210430080857
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Genes and Genomics
2021 Volume.43 No. 8 p.857 ~ p.868
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Long non-coding RNA HOTAIR promotes hepatocellular carcinoma progression by regulating miR-526b-3p/DHX33 axis
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Liu Zhen
Ouyang Guoqing
Lu Wuchang
Zhang Huiming
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Abstract
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Background
Hepatocellular carcinoma (HCC) is one of the most common human cancers. Long non-coding RNAs (lncRNAs) play pivotal roles in progression of various cancers, including HCC.
Objective: We aimed to explore the exact role and underlying mechanism of lncRNA HOX transcript antisense intergenic RNA (HOTAIR) in HCC.
Methods: Quantitative real time polymerase chain reaction (qRT-PCR) was carried out to determine the levels of HOTAIR, DEAH-box helicase 33 (DHX33) and miR-526b-3p. Western blot assay was used to detect the protein level of DHX33. Besides, cell proliferation and apoptosis were assessed by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and flow cytometry analysis, respectively. Cell migration and invasion were detected by transwell assay. The interaction between miR-526b-3p and HOTAIR or DHX33 was predicted by starbase and confirmed by the dual-luciferase reporter assay. Murine xenograft model was established through injecting Huh7 cells transfected with sh-NC or sh-HOTAIR.
Results: The levels of HOTAIR and DHX33 were increased in HCC tissues and cells. Knockdown of either HOTAIR or DHX33 suppressed proliferation, migration and invasion but increased apoptosis in HCC cells. Moreover, DHX33 overexpression reversed the suppressive effect of HOTAIR knockdown on progression of HCC cells. Interestingly, miR-526b-3p could directly bind to HOTAIR, and DHX33 was a direct target of miR-526b-3p. Additionally, interference of HOTAIR restrained the tumor growth by upregulating miR-526b-3p and downregulating DHX33 in vivo.
Conclusions: HOTAIR knockdown suppressed cell proliferation, migration and invasion, and promoted apoptosis via regulating miR-526b-3p/DHX33 axis in HCC cells, providing a potential avenue for treatment of HCC.
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KEYWORD
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Hepatocellular carcinoma, HOTAIR, MiR-526b-3p, DHX33, Cell progression
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