To Identify The Relevance Of Setdb1 Dysregulation In Liver Cancer Pathology And The Underlying Processes

Main Article Content

Chi Pang, Ramesh Babu Manivannan, Nisha Nambiar A, P Gopal Krishnan


Hepatocellular carcinoma (HCC), the most frequent form of liver cancer, is the second biggest cause of cancer-related death worldwide, after lung cancer. Epigenetic changes have recently been implicated in liver cancer, according to growing data. After analysing 591 epigenetic regulators in hepatitis B-associated human HCC with transcriptome sequencing, we discovered that epigenetic regulator dysregulation was frequent in the disease. As a result, we discovered that two histone H3 lysine 9 (H3K9)-specific histone methyltransferases, SETDB1 (SET domain bifurcated 1) and G9a, were highly up-regulated in human HCCs (Euchromatic histone-lysine N-methyltransferase 2, EHMT2). For H3K9 tri- and di-methylation, SETDB1 and G9a are the only two markers that work. Previous epigenetic studies have mostly focused on hypermethylation of promoter DNA. Pathological consequences of histone alterations, in particular the roles of histone methyltransferases such SETDB1 and G9a in human HCC, are still unknown. SETDB1 and G9a, which are overexpressed in human HCC, will be examined to determine their functional significance as well as the underlying mechanisms by which they work.

Multiple HCC sample cohorts corroborated the frequent up-regulation of SETDB1 and found it to be linked with HCC development, cancer aggressiveness, and poor overall survival for patients with HCC. To test this hypothesis, researchers knocked off SETDB1, which prevented HCC cells from proliferating and migrating in culture and from metastasizing to other organs. Many different molecular mechanisms have been proposed to explain why SETDB1 is frequently overexpressed in human HCC, including recurrent gene copy number gain at chromosome 1q21, hyperactivation of SP1 transcription factor, and loss of miR-29, which facilitates SETDB1 overexpression by relieving post-transcriptional repression. Another possibility is that loss of PTEN increases SETDB1 protein levels post-transnationally.

Article Details