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. 2021 Feb 18;18(5):949–970. doi: 10.1080/15548627.2021.1883881

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Figure 2. — The expression of HULC is increased in hepatocellular carcinoma. This lncRNA inhibits METTL3 binding with pri-MIR15A and decreases methylation of pri-MIR15A. Besides, HULC precludes binding of DGCR8 and DROSHA with this pri-miRNA, leading to a significant reduction in the levels of mature MIR15A. Downregulation of this miRNA results in the upregulation of SQSTM1, which contributes to the formation of autophagosome, suppression of PTEN, and induction of cancer [40]. On the other hand, HULC enhances the binding of METTL3 with pri-MIR675 and increases MIR675 levels. This miRNA binds with 3ʹ UTR of HDAC5 mRNA and decreases its expression. Therefore, SIRT1 levels and the formation of autophagosomes are enhanced. This increases CCND1 synthesis and promotes the proliferation of cancer stem cells [134].