HTR1D regulates the PI3K/Akt signaling pathway to impact hepatocellular carcinoma development and resistance to sorafenib

Background Hepatocellular carcinoma (HCC) is a form of cancer with high incidence rates and low survival rates worldwide. Oral sorafenib is a promising therapy for advanced HCC, but resistance to the drug limits its effectiveness. HTR1D, a gene that is highly expressed in HCC, plays a crucial role in the development, drug resistance, and prognosis of the disease. Methods Firstly, the correlation between HTR1D and hepatocellular carcinoma was analyzed by TCGA database, and the expression level of HTR1D in clinical samples was detected by qPCR. Then the siRNA was transfected into HuH-7 and HEP3B cells, and the cell proliferation ability, colony formation ability, migration and invasion ability were detected with or without sorafenib. And the expression of PI3K/Akt pathway was detected by Western Blot. Finally, the potential of HTR1D as a predictive marker for patient prognosis was evaluated by immunohistochemistry Results Analysis of TCGA data showed that methylation of the HTR1D gene was associated with cancer status. Clinical samples confirmed significant differences in HTR1D expression between HCC and adjacent tissues, with higher expression correlating with poorer patient prognosis. Interference with HTR1D gene expression demonstrated its role in promoting HCC proliferation, migration, and drug resistance through the PI3K/Akt pathway. These findings were validated in a mouse model. Immunohistochemical analysis of clinicopathological samples suggested HTR1D could be a valuable prognostic marker for HCC. Conclusion HTR1D is highly expressed in hepatocellular carcinoma tissues, and it can influence hepatocellular carcinoma development and resistance to sorafenib by regulating the PI3K/Akt signaling pathway. In addition, HTR1D has potential as a prognostic indicator.