Long noncoding RNA lncARSR promotes nonalcoholic fatty liver disease and hepatocellular carcinoma by promoting YAP1 and activating the IRS2/AKT pathway
Authors: Yuan Chi
Zhaoyu Liu
He Xin
Ziwen Wang
Zheng Gong
Journal: Journal of Translational Medicine (2020)
Discipline: CLINICAL MEDICINE
Keywords: AKT; Hepatocellular carcinoma; IRS2; Nonalcoholic fatty liver disease; YAP1
Affiliations: Department of Radiology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, 110004, Liaoning, People's Republic of China., Department of Radiology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, 110004, Liaoning, People's Republic of China. .

Abstract:  Background: 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. Methods: 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&amp;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. Results: 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. Conclusion: 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. 

Retracted: No

PubPeer comments:
 Fig 4G.  Cell cycle examined by fow cytometry. Were these hand-drawn? I am fairly sure that cell-count histograms shouldn t have overhangs. ![file] , 
 Clockwise from upper left: Figs 2a d e, 3b, 5d e, 4d a, 3f e d. ![] For comparison, Figs 3i, 4c, 5d e f from [Gou et al (2020)] . To my mind they are drawn from the same limited gamut. ![] Of interest, the Gou et al paper was retracted for outsourcing the WBs to a third-party contractor. , 
 A [19 October 2021] Erratum replaces Fig 4G.  Following publication of the original article [1], the authors identified an error in Fig. 4. The flow cytometry was used to detect the cycle changes of different groups of cells. The authors found that the results were biased due to the improper selection of parameters in flow cytometry. The flow cytometry results were carefully re-analyzed and corrected in Fig. 4g. The incorrect and correct figure are included in this Correction article. The original article has been updated.  the results were biased due to the improper selection of parameters in flow cytometry No, they were hand-drawn. But kudos to the authors for identifying the error. ,