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LncRNA LINC01857 promotes cell growth and diminishes apoptosis via PI3K/mTOR pathway and EMT process by regulating miR-141-3p/MAP4K4 axis in diffuse large B-cell lymphoma

Cancer Gene Therapy volume 28, pages 1046–1057 (2021)Cite this article

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Abstract

LINC01857 has been proven to be involved in glioma and breast cancer. However, the biological function of LINC01857 in diffuse large B-cell lymphoma (DLBCL) is poorly investigated. By accessing to the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEX), LINC01857 expression was found upregulated in both DLBCL tissues and cells. Cell proliferation and flow cytometry assays showed that LINC01857 promoted proliferation and cell cycle, but suppressed apoptosis in DLBCL cells. Bioinformatics analysis and luciferase reporter assay confirmed that LINC01857 may serve as a sponge for miR-141-3p and miR-141-3p may target MAP4K4. Mechanically, the regulatory action of miR-141-3p/MAP4K4 on DLBCL cellular behaviors was regulated by LINC01857. In addition, LINC01857 could increase the activity of PI3K/mTOR pathway and facilitate the EMT process in a miR-141-3p-mediated manner in DLBCL. Our data illustrated that the LINC01857/miR-141-3p/MAP4K4 might function as a promising therapeutic avenue for DLBCL treatment.

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Fig. 1: LINC01857 expression levels in DLBCL tissues and cells.
Fig. 2: Dysregulation of LINC01857 expression could affect the proliferation and apoptosis capabilities of OCI-Ly3 and Raji cells.
Fig. 3: Effect of LINC01857 in cell cycle progression by flow cytometry experiment.
Fig. 4: miR-141-3p was a target of LINC01857 and MAP4K4 was a direct target gene of miR-141-3p in DLBCL.
Fig. 5: MAP4K4 expression was regulated by LINC01857 and miR-141-3p in OCI-Ly3 and Raji cells.
Fig. 6: miR-141-3p and MAP4K4 were involved in the regulation of LINC01857 in DLBCL cells proliferation, apoptosis and cell cycle.
Fig. 7: LINC01857 activated the PI3K/mTOR pathway and promoted EMT process through sponging miR-141-3p in DLBCL.

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Funding

This work was supported by the Natural Science Foundation of Shandong Province, China (Grant Nos. ZR2016HL12 and ZR2015HL075), the National Natural Science Foundation of China (Grant Nos. 81802054 and 81541093), and A Project of Shandong Province Higher Educational Science and Technology Program (Grant Nos. J17KA252).

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  1. These authors contributed equally: Qian Li, Bao Li

Authors and Affiliations

  1. School of Medical Laboratory, Weifang Medical University, Weifang, Shandong, 261053, PR China

    Qian Li

  2. Department of Urology, Weifang People’s Hospital, Weifang, Shandong, 261000, PR China

    Bao Li

  3. School of Clinical Medicine, Weifang Medical University, Weifang, Shandong, 261053, PR China

    Chang-Liang Lu

  4. Department of Pathology, Weifang Maternal and Child Health Care Hospital, Weifang, Shandong, 261011, PR China

    Jing-Ye Wang

  5. Department of Otolaryngology, Weifang People’s Hospital, Weifang, Shandong, 261000, PR China

    Min Gao

  6. Key Lab for Immunology in Universities of Shandong Province, Weifang Medical University, Weifang, Shandong, 261053, PR China

    Wei Gao

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Correspondence to Wei Gao.

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Li, Q., Li, B., Lu, CL. et al. LncRNA LINC01857 promotes cell growth and diminishes apoptosis via PI3K/mTOR pathway and EMT process by regulating miR-141-3p/MAP4K4 axis in diffuse large B-cell lymphoma. Cancer Gene Ther 28, 1046–1057 (2021). https://doi.org/10.1038/s41417-020-00267-4

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