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

Abstract

This 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.