Gain of LINC00624 Enhances Liver Cancer Progression by Disrupting the Histone Deacetylase 6/Tripartite Motif Containing 28/Zinc Finger Protein 354C Corepressor Complex. Issue 5 (16th March 2021)

• Record Type: Journal Article
• Authors: Li, Zhe; Lu, Xinyuan; Liu, Yanfang; Zhao, Jingjing; Ma, Shengzhe; Yin, Haoxiang; Huang, Shenglin; Zhao, Yingjun; He, Xianghuo
• Is Part Of: Hepatology. Volume 73:Issue 5(2021)
• Page Start: 1764
• Page End: 1782
• Publication Date: 2021-03-16
• Subjects: Heart -- Diseases -- Nursing -- Periodicals; Lungs -- Diseases -- Nursing -- Periodicals; Intensive care nursing -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1002/hep.31530
• Languages: English
• ISSNs: 0270-9139

Abstract

Abstract : Background and Aims: Long noncoding RNAs (lncRNAs) are involved in almost every stage of tumor initiation and progression. Here, we have identified an antisense lncRNA, LINC00624, that arises from the antisense strand of chromo‐domain‐helicase‐DNA‐binding protein 1‐like ( CHD1L ), located on chr1q21.1, with significant copy number gain and transcriptional activation of CHD1L and B‐cell CLL/lymphoma 9 protein (BCL9), in hepatocellular carcinoma (HCC). Approach and Results: Overexpression of LINC00624 enhances tumor growth and metastasis in vitro and in vivo . Mechanistically, higher levels of LINC00624 strengthen the interaction between histone deacetylase 6 (HDAC6) and tripartite motif containing 28 (TRIM28), which accelerates HDAC6 ubiquitination and degradation. Moreover, LINC00624 binds to the RBCC domain of TRIM28, inhibits trimer formation, and weakens the interaction between TRIM28 and zinc finger protein 354C (ZNF354C). Thus, LINC00624 overexpression disrupts the formation of the HDAC6‐TRIM28‐ZNF354C transcriptional corepressor complex, resulting in the dissociation of the complex from the promoter of CHD1L and BCL9, thereby removing transcription inhibition. Conclusions: Our findings suggest that LINC00624 acts as a molecular decoy that sequesters the HDAC6‐TRIM28‐ZNF354C transcriptional corepressor complex away from the specific genomic loci, and that it can potentially be a therapeutic target in HCC.