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RETRACTED ARTICLE: HBx/ERα complex-mediated LINC01352 downregulation promotes HBV-related hepatocellular carcinoma via the miR-135b-APC axis

Oncogene volume 39, pages 3774–3789 (2020)Cite this article

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This article was retracted on 26 June 2023

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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.

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Fig. 1: LINC01352 is downregulated by HBV/HBx in HCC cells and tissues.
Fig. 2: HBx suppresses LINC01352 promoter activity by forming a complex with ERα.
Fig. 3: LINC01352 is involved in HBx-induced HCC cell proliferation and metastasis.
Fig. 4: LINC01352 regulates miR-135b expression and activity via a direct interaction.
Fig. 5: miR-135b and LINC01325 are inversely related in HBV-related HCC.
Fig. 6: LINC01352 blocks the repression of APC by suppressing miR-135b.
Fig. 7: APC downregulation is associated with LINC0135-miR135b sponge in HBV-related HCC.
Fig. 8: The suppressive function of LINC01352 is mediated by miR-135b in vitro and in vivo.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81702404, 81572407, 81672405 and 81372565), the Natural Science Foundation of Guangdong Province, China (No. 2016A030311051 and 2017A030313536) and the Guangzhou Science Research Project (No. 201607010225).

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Author notes

  1. These authors contributed equally: Pinbo Huang, Qiaodong Xu, Yongcong Yan, Yingjuan Lu

Authors and Affiliations

  1. Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China

    Pinbo Huang, Yongcong Yan, Zhigang Hu, Heyun Zhang, Kai Mao, Jianlong Zhang, Jie Wang & Zhiyu Xiao

  2. 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

    Pinbo Huang, Yongcong Yan, Zhigang Hu & Zhiyu Xiao

  3. Department of Biliary-Pancreatic Minimally Invasive Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China

    Qiaodong Xu

  4. Department of Stomatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China

    Yingjuan Lu

  5. Department of Ultrasonography, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China

    Bing Ou

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Contributions

PH, JW and ZX participated in the study design. PH, QX, YY, YL, ZH and JZ carried out the in vitro and in vivo experiments and data analysis. PH, QX, BO, HZ and KM performed the clinical data analysis. PH and QX wrote the manuscript. All the authors read and approved the final manuscript.

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Correspondence to Jie Wang or Zhiyu Xiao.

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This article has been retracted. Please see the retraction notice for more detail: https://doi.org/10.1038/s41388-023-02753-z

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Huang, P., Xu, Q., Yan, Y. et al. RETRACTED ARTICLE: HBx/ERα complex-mediated LINC01352 downregulation promotes HBV-related hepatocellular carcinoma via the miR-135b-APC axis. Oncogene 39, 3774–3789 (2020). https://doi.org/10.1038/s41388-020-1254-z

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