Comprehensive transcriptome profiling of BET inhibitor-treated HepG2 cells

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and poor prognosis. Emerging evidence suggests that epigenetic alterations play a crucial role in HCC, suggesting epigenetic inhibition as a promising therapeutic approach. Indeed, the bromodomain and extra-terminal (BET) inhibitors inhibit the proliferation and invasion of various cancers but still lack a strong mechanistic rationale. Here, we identified the differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) in human HCC cell line HepG2 treated with the BET inhibitors, JQ1, OTX015, or ABBV-075. We analyzed the correlation between DEmRNAs and DElncRNAs in common for the three inhibitors based on their expression profiles and performed functional annotation pathway enrichment analysis. Most of these shared DEmRNAs and DElncRNAs, including some novel transcripts, were downregulated, indicating decreased proliferation/adhesion and increased apoptosis/inflammation. Our study suggests that BET proteins play a crucial role in regulating cancer progression-related genes and provide a valuable resource for novel putative biomarkers and therapeutic targets in HCC.

Epigenetic modulation through BET bromodomain inhibitors as a novel therapeutic strategy for progranulin-deficient frontotemporal dementia

“…Indeed, this work suggests that small molecule BET inhibitors, despite their effective disruption of bromodomain-acetyl lysine binding, do not invariably inhibit the transcription-enhancing function of BET family proteins. Consistent with this hypothesis, in various cell types, BET inhibition causes downregulation of the majority of genes, while a minority of genes do appear to be upregulated on rapid timescales 64 , 84 .…”

Newly repopulated spinal cord microglia exhibit a unique transcriptome and correlate with pain resolution

“…We identified an additional sub-cluster, cluster 4 (81 nuclei), with a signature similar to reactive microglia with GO terms such as “cell activation”, “regulation of cell motility”, and a cluster-unique term “inflammatory process”, with key genes significantly expressed such as TLR2 and CYBB (also known as NOX2 ), both potent neuroinflammatory-associated genes expressed by microglia(41, 42) (Supplemental Figure 10b). Additionally, a top differentially expressed gene in cluster 4 was AC083837.1 (p-value adj = 1.17E-100), a novel long noncoding RNA induced in the human microglial cell line (HMC3) in response to LPS treatment(43) (Supplemental Figure 10b). Importantly, we further identified a large nuclei cluster that represented homeostatic microglia (cluster 1, 730 nuclei), with cluster-unique terms “myeloid cell homeostasis” and “regulation of supramolecular fiber organization” as well as “regulation of cell adhesion” and “cell junction organization”.…”

Identification of differentially expressed mRNA/lncRNA modules in acutely regorafenib-treated sorafenib-resistant Huh7 hepatocellular carcinoma cells

“…Where added, DMSO or regorafenib were present for the last 24 hours preceding the RNA extraction. The RNA library was created as previously described [ 14 ]. Briefly, RNA was extracted using RNAiso Plus (Takara, Shiga, Japan) and the RNeasy Mini Kit (QIAGEN Inc., Hilden, Germany), and rRNA was depleted using the RiboMinus Eukaryote kit (Invitrogen, Carlsbad, CA, USA).…”