4.7 Article

Exploring the oncogenic roles of LINC00857 in pan-cancer

期刊

FRONTIERS IN PHARMACOLOGY
卷 13, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.996686

关键词

LINC00857; biomarker; bioinformatics; tumor immunity; pan-cancer

资金

  1. National Natural Science Foundation of China [81902404]
  2. Natural Science Foundation of Shandong Province [ZR2019BH009, ZR2020QH096]
  3. Project of Shandong Province medical science technology development plan [2017WS403, 2019WS601, 202103030672]
  4. Introduction Plan of Young Creative Talents in Colleges and Universities of Shandong Province [205]

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This research analyzed the expression characteristics of LINC00857 in multiple cancers and found that high expression of LINC00857 was associated with poor prognosis and negatively correlated with immune cell infiltration and immune checkpoint gene expression. The study also found that LINC00857 was negatively associated with immunotherapy response in colorectal cancer and may accelerate cancer progression by regulating the ferroptosis pathway and glycolipid metabolism.
Although aberrant LINC00857 expression may play a key role in oncogenesis, no research has analyzed the pan-cancer oncogenic roles of LINC00857, particularly in tumor immunology. Here, we integrated data from several databases to analyze the characteristics of LINC00857 in pan-cancer. We found that LINC00857 was overexpressed and correlated with a poor prognosis in a variety of cancers. Furthermore, high-expression of LINC00857 was negatively associated with immune cell infiltration and immune checkpoint gene expression. Notably, LINC00857 expression was negatively related to microsatellite instability and tumor mutation burden in colorectal cancer, implying poor reaction to immunotherapy when LINC00857 was highly expressed. Targeting LINC00857 could dramatically impair the proliferative ability of colorectal cancer cells. After RNA-sequencing in HCT116 cells, gene set enrichment analysis showed that LINC00857 may accelerate cancer progression by inhibiting the ferroptosis pathway and promoting glycolipid metabolism in colorectal cancer. Screening by weighted gene co-expression network analysis determined PIWIL4 as a target of LINC00857, which also performed an immunosuppressive role in colorectal cancer. Based on the structure of PIWIL4, a number of small molecule drugs were screened out by virtual screening and sensitivity analysis. In summary, LINC00857 expression was closely correlated with an immunosuppressive microenvironment and may be a novel diagnostic and prognostic biomarker for diverse cancers. The LINC00857/PIWIL4 axis may be predictive biomarkers for immunotherapy and valuable molecular targets for malignant tumors.

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