Investigating the miRNA of the Chinese herb Gecko on the cross-species regulation network of hepatocellular carcinoma

Abstract

Abstract Gecko is a traditional Chinese herb that has been extensively documented as a treatment for various illnesses, including cancer, for thousands of years in ancient Chinese literature. The development of Chinese medicinal preparations and the role of small molecule active ingredients in Chinese medicine have recently emerged as new research hotspots. However, the potential cross-species regulatory mechanisms of microRNAs (miRNAs) from Gecko components in hepatocellular carcinoma (HCC) are not fully understood. In this study, we isolated and extracted total RNA from Chinese herbal Gecko tablets after powdering and screened the Gecko miRNA expression dataset after high-throughput sequencing to compare with the survival-related differentially expressed miRNA dataset in human HCC to identify new Gecko and HCC survival-related miRNA-mRNA regulatory networks. The miR-100-5p, miR-99a-5p, and miR-101-3p were identified as critical miRNAs for the role of Geckos in human HCC. Stepwise prediction and validation, nine downstream mRNAs (EZH2, KPNA2, LMNB1, LRRC1, MRGBP, SMARCD1, STMN1, SUB1, and UBE2A) were found to be determined as key miRNAs interacting with essential genes that interact with each other. A miRNA-mRNA regulatory network consisting of these key genes was constructed, and GO, KEGG enrichment analysis indicated that these key mRNAs might be associated with the suppression and progression of hepatocellular carcinoma. Importantly, immune infiltration analysis showed that the miRNA network was significantly associated with the infiltration abundance of multiple immune cells. These findings suggest that Gecko miRNAs may inhibit HCC progression and treat HCC by targeting critical miRNA-mRNA networks for cross-species regulation. It also provides a reference for future research and new drug development.