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Knockdown of LINC00467 contributed to Axitinib sensitivity in hepatocellular carcinoma through miR-509-3p/PDGFRA axis

Gene Therapy volume 28, pages 634–645 (2021)Cite this article

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Abstract

Hepatocellular carcinoma (HCC) is a common histological class of primary liver cancer with dismal prognosis. Long noncoding RNAs (lncRNAs) are increasingly documented as participators in cancers. Present study aimed to explore the role of long intergenic nonprotein-coding RNA 467 (LINC00467) in HCC. LINC00467 was upregulated in HCC samples in TCGA database, and was confirmed to be elevated in HCC cell lines. Functionally, LINC00467 depletion impeded proliferation and invasion, induced apoptosis, and promoted cellular sensitivity to Axitinib in HCC. Mechanistically, LINC00467 performed as a sponge of microRNA (miR)-509-3p and upregulated the expression of platelet-derived growth factor receptor alpha (PDGFRA) in HCC cells. In conclusion, our study illustrated that LINC00467 promoted proliferation and invasion, impedes apoptosis, and contributed to Axitinib resistance of hepatocellular carcinoma through miR-509-3p/PDGFRA, indicating LINC00467 as a promising biological target for HCC treatment.

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Fig. 1: LINC00467 was upregulated in HCC and silence of LINC00467 inhibited HCC progression.
Fig. 2: LINC00467 knockdown sensitized HCC cells to Axitinib.
Fig. 3: LINC00467 targeted miR-509-3p in HCC.
Fig. 4: LINC00467 upregulated PDGFRA by targeting miR-509-3p in HCC.
Fig. 5: LINC00467 positively regulated HCC progression and resistance to Axitinib through PDGFRA.
Fig. 6: In vivo assays.
Fig. 7: Schematic diagram.

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Acknowledgements

Thank you for all participators in this study.

Funding

This study was supported by Natural Science Foundation of Heilongjiang Province (NO.: LH2019H077).

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Authors and Affiliations

  1. Department of Interventional and Vascular, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang, China

    Wei Li, Wei Chen, Wenling Man, Qiang Fu, Hongtong Tan, Huanqing Guo, Jingnan Zhou & Po Yang

  2. Department of Neoplastic Hematologic Disorder, Hegang Mine Crane Hospital, Hegang, 154100, Heilongjiang, China

    Yufeng He

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Contributions

WL designed this study. WL and YH contributed to experiments and interpretation. WC, WM, and QF were responsible for the collection of experimental materials. HT and HG took charge of statistical analysis. WL, JZ, and PY wrote the article. Each author conduced to this study and provided valuable advice for this paper.

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Correspondence to Po Yang.

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Li, W., He, Y., Chen, W. et al. Knockdown of LINC00467 contributed to Axitinib sensitivity in hepatocellular carcinoma through miR-509-3p/PDGFRA axis. Gene Ther 28, 634–645 (2021). https://doi.org/10.1038/s41434-020-0137-9

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