Small RNA sequencing explores a potential regulatory network mediated by Gecko miRNA affecting the prognosis of hepatocellular carcinoma

Gecko has been widely documented in ancient Chinese literature as a anti-tumor agents for various illnesses for thousands of years, while a few studies have examined the antitumor effects of gecko proteins on several cancers. The effect of gecko microRNAs (miRNAs) on hepatocellular carcinoma (HCC) has not yet been reported. This study was designed to identify miRNAs in Gecko through small RNA sequencing and utilize bioinformatics techniques to construct a potential regulatory network and explore the possible mechanisms of exogenous miRNAs involved in hepatocellular carcinoma. In this study, we extracted total RNA from Gecko tablets and screened the gecko miRNA expression dataset after high-throughput sequencing. Bioinformatics analysis were used to identify novel gecko and HCC survival-related miRNA-mRNA cross-species regulation networks. The miR-100-5p, miR-99a-5p, and miR-101-3p were identified as critical miRNAs for the role of Geckos in HCC. Nine downstream mRNAs (EZH2, KPNA2, LMNB1, LRRC1, MRGBP, SMARCD1, STMN1, SUB1, and UBE2A) were identified as target genes for critical miRNAs. A miRNA-mRNA regulatory network was constructed, and GO, KEGG enrichment analysis showed these key mRNAs might be associated with the suppression and progression of HCC. The novel network significantly correlated with the abundance of multiple immune cells, as determined by immune infiltration analysis. These findings suggest that Gecko may inhibit progression and treat HCC by targeting critical miRNA-mRNA networks for cross-species regulation. It also provides a reference for future research and development of Chinese medicine.