LINC00892 inhibits hepatocellular carcinoma progression through SBDS/EIF6‐mediated ribosomal stress and interacting with the immune microenvironment

Hepatocellular carcinoma (HCC) is a pernicious tumor with high heterogeneity and bleak prognosis, in which the immune microenvironment (IM) plays important roles. The underlying mechanisms of IM should be deeply investigated to discover novel therapeutic targets. In this study, we identified one long noncoding RNA associated with T cell activation, LINC00892, and deeply explored its association with the progression, prognosis, and the IM of HCC. We identified its interacted proteins and confirmed its regulatory mechanisms in HCC development. The dysregulated immune cell infiltration by LINC00892 was also identified. The results of bioinformatics analysis demonstrated that LINC00892 was downregulated in HCC tissues, and its high expression was connected with early TNM stage and better outcome. Further in vitro cellular experiments showed that LINC00892 overexpression significantly inhibited proliferation, migration, invasion, and colony formation abilities of HCC cells, which was also validated by in vivo animal model. Furthermore, high expression of LINC00892 was associated with incremental infiltration of CD8 + T cells, B cells, and macrophages, indicating its association with a better response to immunotherapy. Mechanistic analysis indicated that LINC00892 induces ribosomal stress by suppressing Shwachman‐Bodian Diamond Syndrome (SBDS) expression, further preventing the nuclear translocation of EIF6 and activating the p53 pathway, thereby inhibiting tumor progression. In summary, LINC00892 activates the p53 pathway through ribosomal stress mediated by SBDS/EIF6, regulates HCC progression, and probably enhances the infiltration of immune cells, showing potential application value as a prognostic indicator and immunotherapy orientation for HCC.