Abstract
Long non-coding RNAs (lncRNAs) have been implicated in liver carcinogenesis. We previously showed that the induction of lncRNA-uc002mbe.2 is positively associated with the apoptotic effect of trichostatin A (TSA) in hepatocellular carcinoma (HCC) cells. The current study further analyzed the role of uc002mbe.2 in TSA-induced liver cancer cell death. The level of uc002mbe.2 was markedly increased by TSA in the cytoplasm of HCC cells. Knockdown of uc002mbe.2 prohibited TSA-induced G2/M cell cycle arrest, p21 induction, and apoptosis of Huh7 cells and reversed the TSA-mediated decrease in p-AKT. RNA pull-down and RNA-binding protein immunoprecipitation (RIP) assays revealed that TSA induced an interaction between uc002mbe.2 and heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) in Huh7 cells. This interaction mediated AKT deactivation and p21 induction in liver cancer cells. In an athymic xenograft mouse model, knockdown of uc002mbe.2 significantly prohibited the TSA-mediated reduction in tumor size and weight. In addition, the ability of TSA to reduce hnRNPA2B1 and p-AKT levels and induce p21 in the xenograft tumors was prevented by uc002mbe.2 knockdown. Therefore, the interaction of uc002mbe.2 and hnRNPA2B1 in mediating AKT deactivation and p21 induction is involved in the cytostatic effect of trichostatin in liver cancer cells.
Highlights
Long non-coding RNAs have many functions, such as modulating gene transcription, epigenetic signaling, and protein trafficking (Evans et al, 2016; Su et al, 2016; Chandra Gupta and Nandan Tripathi, 2017)
Several Long non-coding RNAs (lncRNAs) have been implicated in chemotherapeutic sensitivity and resistance in hepatocellular carcinoma (HCC), the mechanisms underlying this drug sensitivity remain to be fully elucidated (Panzitt et al, 2007; Li et al, 2017; Xiong et al, 2017)
Our data showed that knockdown uc002mbe.2 prevented trichostatin A (TSA)-induced apoptosis and G2/M cell cycle arrest in HCC cells
Summary
Long non-coding RNAs (lncRNAs) have many functions, such as modulating gene transcription, epigenetic signaling, and protein trafficking (Evans et al, 2016; Su et al, 2016; Chandra Gupta and Nandan Tripathi, 2017). LncRNA-Xist (X-inactive specific transcript) was identified as a biomarker that predicts the response of breast cancer cell lines (BCLs) to histone deacetylase inhibitors (HDACi) (Salvador et al, 2013). This previous study demonstrated that low Xist expression predicts the response to HDACi in patient-derived xenografts and is associated with a significant reduction of the breast cancer stem cells (Salvador et al, 2013). LncRNAs are novel therapeutic targets that mediate the antitumor effects of drugs such as HDACi
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
