HBx/ERα complex-mediated LINC01352 downregulation promotes HBV-related hepatocellular carcinoma via the miR-135b-APC axis
Authors: Yingjuan Lu
Jie Wang
Yongcong Yan
Bing Ou
Zhigang Hu
Pinbo Huang
Heyun Zhang
Qiaodong Xu
Jianlong Zhang
Kai Mao
Zhiyu Xiao
Journal: Oncogene (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Hepatitis B virus; HBV; hepatocarcinogenesis; hepatocellular carcinoma; long non-coding RNAs
Affiliations: Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China., Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China., Department of Biliary-Pancreatic Minimally Invasive Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China., Department of Stomatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China., Department of Ultrasonography, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China., Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. ., Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. .

Abstract:  Hepatitis B virus (HBV) infection plays an important role in hepatocarcinogenesis, especially in hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) have emerged as crucial biomarkers and regulators in many cancers. Novel lncRNAs involved in the initiation and progression of HBV-related hepatocellular carcinoma (HCC) need to be investigated. Here, we report that the long non-coding RNA LINC01352 is markedly downregulated by HBV/HBx (HBV X protein) in HCC cells and clinical samples. The LINC01352 expression level in HCC is an independent prognostic factor for survival. We found that HBx suppresses LINC01352 promoter activity by forming a complex with the estrogen receptor (ERα). Furthermore, using a combination of in vitro and in vivo studies, we confirmed that HBx promotes HCC cell growth and metastasis by inhibiting LINC01352 expression. Further investigation revealed that the downregulation of LINC01352, which acts as an endogenous sponge, increases the expression of miR-135b, leading to the reduced production of adenomatous polyposis coli (APC), consequently activating Wnt/β-catenin signalling to facilitate tumour progression. These findings strongly suggest that the LINC01352-miR-135b-APC axis regulated by the HBx/ERα complex acts as an important pathogenic factor for tumour progression, which may help provide a theoretical basis for the identification of new therapeutic targets for HBV-related HCC. 

Retracted: No

PubPeer comments:
 Red boxes: In Figure 8B, the LINC01352+miR-135b panel appears to be a part of the HBx panel in Figure 3C![file] ![file] , 
 #1 More image manipulation with rotation showed: Except the figure reuse as pointed out by #1 Atractolytocestus huronensis (red box), the **yellow marked box** also showed another kind of image manipulation by vertical flipping: Details as follows: ![file] ![file] , 
 **Figure 1H** and **Figure 6B**, WB bands reuse was detected: ![file] , 
 **Figure 3D**, the transwell assay for the invasion capability analysis, the authors have concluded that the group of sh-LINC01352 was associated with the most invasive characteristic as showed by the right plot, however, images in the left did not indicate a significantly different invasive capability between **sh-LINC01352 and sh-NC**. ![file] ![file] Please be noted that the number of invasive cells in the sh-LINC01352 group was almost as twice as much when compared with that in the sh-NC group. **As showed by the right plot, that is 260 vs 150** , 
 #2 **More figure overlaps could be found**: **Figure 3D**: ![file] ![file] ,