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FOXO3-induced lncRNA LOC554202 contributes to hepatocellular carcinoma progression via the miR-485-5p/BSG axis

Cancer Gene Therapy volume 29, pages 326–340 (2022)Cite this article

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A Correction to this article was published on 21 April 2022

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Abstract

Long non-coding RNAs (LncRNAs) have played very important roles in the malignancy behaviors of hepatocellular carcinoma (HCC). LncRNA LOC554202 (LOC554202) was a newly identified tumor-related lncRNA. However, its expression and function in HCC remained unknown. In this study, we firstly reported that LOC554202 expression was distinctly upregulated in HCC specimens and cell lines. Clinical assays indicated that increased LOC554202 expression had a diagnostic value for HCC patients and was positively associated with advanced stages and poor clinical prognosis. Additionally, forkhead box O3(FOXO3) could bind directly to the LOC554202 promoter region and activate its transcription. Functionally, we observed that knockdown of LOC554202 suppressed the proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) progress of HCC cells, and promoted apoptosis. Mechanistically, LOC554202 competitively bound to miR-485-5p and prevented the suppressive effects of miR-485-5p on its target gene basigin (BSG), which finally led to HCC metastasis, EMT, and docetaxel chemoresistance. Our data demonstrated that FOXO3-induced LOC554202 contributed to HCC progression by upregulating BSG via competitively binding to miR-485-5p, which suggested that the regulation of the FOXO3/LOC554202/miR-485-5p/BSG axis may have beneficial effects in the treatment of HCC.

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Fig. 1: The distinct upregulation of LOC554202 in HCC patients and its clinical significance.
Fig. 2: LOC554202 is activated by FOXO3 in HCC.
Fig. 3: The effect of LOC554202 on HCC cell proliferation and apoptosis.
Fig. 4: Knockdown of LOC554202 suppressed the migration and invasion of HCC cells.
Fig. 5: LOC554202 competitively sponged miR-485-5p.
Fig. 6: BSG was a target gene for miR-485-5p.
Fig. 7: Deficiency of miR-485-5p attenuates the regulatory effect of LOC554202 knockdown on the progression of HCC cells.
Fig. 8: Hypothetical model for LOC554202 function in HCC.

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Data availability

The data used to support the findings of this study are available from the corresponding author upon request

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Acknowledgements

This work was supported by the Natural Science Foundation Youth Project of Shaanxi Province (No. 2018JQ8014) and the Subject Innovation Team of Shaanxi University of Chinese Medicine (2019-YL06).

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  1. These authors contributed equally: Lin Yang, Wan-li Deng

Authors and Affiliations

  1. Department of Hepatobiliary Surgery, The Xianyang Central Hospital, Xianyang, Shaanxi, China

    Lin Yang, Bao-guo Zhao, Yao Xu & Xiao-wen Wang

  2. Department of Oncology, The Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Putuo, Shanghai, China

    Wan-li Deng

  3. Department of Oncology, The Affiliated Hospital of the Shaanxi University of Traditional Chinese Medicine, Xianyang, Shaanxi, China

    Yu Fang & Hai-juan Xiao

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Contributions

LY, W-lD, and H-jX: designed the experiment, interpreted the data, and prepared the manuscript. B-gZ, YX, X-wW, YF, and LY conducted the experiment, collected the data, and reviewed the manuscript.

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Correspondence to Hai-juan Xiao.

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Our study was approved by the ethics review board of the Affiliated Hospital of the Shaanxi University of Traditional Chinese Medicine.

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Yang, L., Deng, Wl., Zhao, Bg. et al. FOXO3-induced lncRNA LOC554202 contributes to hepatocellular carcinoma progression via the miR-485-5p/BSG axis. Cancer Gene Ther 29, 326–340 (2022). https://doi.org/10.1038/s41417-021-00312-w

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