Abstract
BackgroundNonalcoholic fatty liver disease (NAFLD) is the main cause for hepatocellular carcinoma (HCC). This study was intended to identify the function of long non-coding RNA (lncRNA) lncARSR in NAFLD and its role in human HCC cells (HepG2) proliferation and invasion.MethodsLncARSR expression was detected both in high fatty acid-treated HepG2 cells and NAFLD mouse model. After gain- and loss-of-function approaches in high fatty acid-treated HepG2 cells and NAFLD mice, lipid accumulation in livers from NAFLD mice and high fatty acid-treated cells was determined by H&E staining, Oil Red-O staining or Nile Red staining respectively. Expression of YAP1, adipogenesis- (Fasn, Scd1 and GPA) and IRS2/AKT pathway-related genes was measured. Cell proliferation was monitored by MTT and soft-agar colony formation assays, cell cycle was analyzed by flow cytometry, and cell invasion was examined by transwell assay. The tumor weight and volume were then measured through in vivo xenograft tumor model after silencing lncARSR.ResultsLncARSR was highly expressed in high fatty diet (HFD)-fed mice and high fatty acid-treated HepG2 cells. LncARSR was observed to bind to YAP1, which inhibited phosphorylation nuclear translocation. LncARSR activated the IRS2/AKT pathway by reducing YAP1 phosphorylation, and further increased lipid accumulation, cell proliferation, invasion and cell cycle. Silencing lncARSR in HFD-fed mice alleviated NAFLD by regulating YAP1/IRS2/AKT axis.ConclusionSilencing lncARSR suppressed the IRS2/AKT pathway, consequently reducing HCC cell proliferation and invasion and inhibiting lipid accumulation in NAFLD mice by downregulating YAP1, which suggests a clinical application in treating NAFLD.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is the main cause for hepatocellular carcinoma (HCC)
We investigated the effects of lncARSR/ YAP1 on NAFLD, and identified that lncARSR promoted NAFLD through YAP1 and the insulin receptor substrate 2 (IRS2)/AKT pathway, providing a novel insight into NAFLD treatment
LncARSR expression is increased in both high‐fat‐fed mice and hepatocellular carcinoma cells (HepG2) cells treated with high fatty acid It was reported that over-expressing lncARSR accelerated the accumulation of liver fat in vivo and in vitro, while silencing lncARSR led to reduction of liver fat, which suggested that lncARSR may participate in regulation of liver fat in NAFLD [7]
Summary
Nonalcoholic fatty liver disease (NAFLD) is the main cause for hepatocellular carcinoma (HCC). This study was intended to identify the function of long non-coding RNA (lncRNA) lncARSR in NAFLD and its role in human HCC cells (HepG2) proliferation and invasion. Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease commonly seen in over-weight or obese people. Almost 90% of obese people have been diagnosed with diseases associated with fatty liver [1]. Long non-coding RNAs (lncRNAs) may act as potential markers for prognosis and progression of liver diseases and as direct targets for therapeutic. Several lncRNAs have been proved to be associated with liver diseases [5]. The role of lncARSR in NAFLD is less clear
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