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

• Published in: Cancer science 2023-11, Vol.114 (11), p.4329-4342
• Main Authors: Zhang, Xiaoxia, Cong, Peilin, Tian, Li, Zheng, Yinggang, Zhang, Hong, Liu, Qiong, Wu, Tingmei, Zhang, Qian, Wu, Huanghui, Huang, Xinwei, Xiong, Lize
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Antineoplastic drugs; Antitumor agents; Biosynthesis; Cell death; Cholecystokinin; Correlation analysis; Datasets; DNA methylation; Drug development; Gene expression; Genomics; Head & neck cancer; Hepatitis; Hepatocellular carcinoma; Hepatocytes; Immune checkpoint; Immunosuppressive agents; Ligands; Liver cancer; Mann-Whitney U test; Medical prognosis; MicroRNAs; Original; Prognosis; Proteins; Ribonucleic acid; RNA; Survival analysis; Therapeutic targets; Tumor cell lines; Tumors; Up-regulation; Wound healing
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.15933

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.