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. LncARSR 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. LncARSR 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. Silencing 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.

中文翻译：

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长链非编码 RNA lncARSR 通过促进 YAP1 和激活 IRS2/AKT 通路促进非酒精性脂肪肝和肝细胞癌。

非酒精性脂肪性肝病（NAFLD）是肝细胞癌（HCC）的主要原因。本研究旨在确定长链非编码 RNA (lncRNA) lncARSR 在 NAFLD 中的功能及其在人 HCC 细胞 (HepG2) 增殖和侵袭中的作用。在高脂肪酸处理的 HepG2 细胞和 NAFLD 小鼠模型中均检测到 LncARSR 表达。在高脂肪酸处理的 HepG2 细胞和 NAFLD 小鼠的功能获得和丧失方法后，通过 H&E 染色、油红-O 染色或尼罗红确定 NAFLD 小鼠和高脂肪酸处理的细胞肝脏中的脂质积累分别染色。测量了 YAP1、脂肪生成（Fasn、Scd1 和 GPA）和 IRS2/AKT 通路相关基因的表达。通过 MTT 和软琼脂集落形成测定监测细胞增殖，通过流式细胞术分析细胞周期，用transwell法检测细胞侵袭。然后在沉默 lncARSR 后通过体内异种移植肿瘤模型测量肿瘤重量和体积。LncARSR 在高脂肪饮食 (HFD) 喂养的小鼠和高脂肪酸处理的 HepG2 细胞中高度表达。观察到 LncARSR 与 YAP1 结合，从而抑制磷酸化核转位。LncARSR 通过降低 YAP1 磷酸化激活 IRS2/AKT 通路，进一步增加脂质积累、细胞增殖、侵袭和细胞周期。在 HFD 喂养的小鼠中沉默 lncARSR 通过调节 YAP1/IRS2/AKT 轴来减轻 NAFLD。沉默 lncARSR 抑制 IRS2/AKT 通路，从而通过下调 YAP1 减少 HCC 细胞增殖和侵袭并抑制 NAFLD 小鼠的脂质积累，这表明在治疗 NAFLD 中的临床应用。