Genomic gain/methylation modification/hsa‐miR‐132‐3p increases RRS1 overexpression in liver hepatocellular carcinoma

Abstract

AbstractThis study aimed to determine the upstream regulatory factors affecting ribosome biogenesis regulator 1 homolog (RRS1) expression and the development and prognosis of liver hepatocellular carcinoma (LIHC). The expression profiles of RRS1 were evaluated in pan‐cancer tissues and liver tumor cell lines. The associations of RRS1 with pan‐cancer survival, immune infiltrations, immune checkpoints, and drug sensitivity were identified. We explored the potential upstream regulatory mechanisms of RRS1 expression. Hsa‐miR‐132‐3p knockdown, CCK‐8 assays, transwell, and wound healing assays were performed to validate the regulatory effect of hsa‐miR‐132‐3p on RRS1 expression and the development of LIHC. Our findings demonstrated that RRS1 was significantly elevated in 27 types of cancers. RRS1 predicts a poor outcome of LIHC, lung adenocarcinoma, head and neck cancer, and kidney papillary cell carcinoma. RRS1 expression showed a significant association with immune cell infiltrates and the expression of immune checkpoints‐related genes in LIHC tissues. Increased RRS1 expression may have a negative effect on these anticancer drugs of LIHC. Low methylation of the RRS1 promoter and its genomic gain may elevate RRS1 expression and predict poor prognosis for LIHC. Increased hsa‐miR‐132‐3p expression may elevate RRS1 expression and result in poor prognosis for LIHC. Hsa‐miR‐132‐3p inhibition can decrease RRS1 expression and the development of liver tumor cell lines. Low methylation of the RRS1 promoter, RRS1 genomic gain, and hsa‐miR‐132‐3p upregulation in LIHC may promote RRS1 upregulation and thus lead to the development and poor prognosis for LIHC. RRS1 is a promising therapeutic target for LIHC.