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Wenxia Shi,1,* Jingjing Dong,1,* Hailin Li,2 Li Jing,1 Hua Guo,1 Tong Liu,1 Chenglong Li,1 Yingtang Gao1 1Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin Institute of Hepatobiliary Disease, Nankai University Affiliated Third Center Hospital, Tianjin, People’s Republic of China; 2The Third Central Clinical College of Tianjin Medical University, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yingtang Gao, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin Institute of Hepatobiliary Disease, Nankai University Affiliated Third Center Hospital, Jintang Road 83#, Hedong District, Tianjin, 300170, People’s Republic of China, Email gaoyt816@163.com; 31017014@nankai.edu.cnPurpose: Let-7, a family of microRNA (miRNA) that regulates the timing of cell division, is associated with tumorigenesis and tumor progression. The factors that regulate let-7 and affect the prognosis of hepatocellular carcinoma (HCC) warrant further investigation.Patients and Methods: In this study, we first utilized the data from The Cancer Genome Atlas (TCGA) and employed bioinformatics methods to analyze the expression and function of let-7 in HCC. Subsequently, we retrieved the long non-coding RNAs (lncRNAs) that regulate let-7 from the StarBase database. Finally, through bioinformatics analysis of the TCGA-LIHC data and validation with clinical samples, we explored the relationship between let-7 and its related lncRNAs and clinical indicators such as HCC recurrence and survival.Results: Let-7c was significantly downregulated in HCC, regulating tumor progression via pathways like PI3K-Akt and tumor-related miRNAs. LncRNAs SNHG16 negatively regulated let-7c expression in HCC (r = − 0.160, p = 0.002). Both bioinformatics analysis and clinical sample validation revealed that high SNHG16 expression in HCC tissues was associated with shorter disease-free survival (HR = 1.711, 95% CI: 1.144– 2.559, p = 0.009), higher recurrence rates (p < 0.001), and shorter overall survival (HR = 1.837, 95% CI: 1.283– 2.629, p = 0.001).Conclusion: SNHG16 negatively regulates let-7c and serves as a prognostic biomarker for HCC recurrence and survival.Keywords: let-7, long noncoding RNAs, hepatocellular carcinoma, prognosis |